token_classification/10-1016_j-molcel-2011-04-029.xml

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<article doi="10.1016/j.molcel.2011.04.029" abstract="Autophagy, a major degradation process for long-lived and aggregate-prone proteins, affects various human processes, such as development, immunity, cancer, and neurodegeneration. Several autophagy regulators have been identified in recent years. Here we show that nitric oxide (NO), a potent cellular messenger, inhibits autophagosome synthesis via a number of mechanisms. NO impairs autophagy by inhibiting the activity of S-nitrosylation substrates, JNK1 and IKKβ. Inhibition of JNK1 by NO reduces Bcl-2 phosphorylation and increases the Bcl-2-Beclin 1 interaction, thereby disrupting hVps34/Beclin 1 complex formation. Additionally, NO inhibits IKKβ and reduces AMPK phosphorylation, leading to mTORC1 activation via TSC2. Overexpression of nNOS, iNOS, or eNOS impairs autophagosome formation primarily via the JNK1-Bcl-2 pathway. Conversely, NOS inhibition enhances the clearance of autophagic substrates and reduces neurodegeneration in models of Huntington's disease. Our data suggest that nitrosative stress-mediated protein aggregation in neurodegenerative diseases may be, in part, due to autophagy inhibition."><fig id="4352"><title></title><label>Figure 1</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4352"/><sd-panel panel_id="13375"><p>(A) <sd-tag id="sdTag1" source="sdapi" category="assay" entity_type="" role="" text="Immunoblot" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoblot</sd-tag> analysis with anti-<sd-tag id="sdTag2" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q9GZQ8///Q9BXW4///Q9H492" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="MAP1LC3B///MAP1LC3C///MAP1LC3A" ext_tax_ids="9606///9606///9606" ext_tax_names="Homo sapiens///Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> antibody shows that NO donors reduced <sd-tag id="sdTag8" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q62625///Q6XVN8" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3b///Map1lc3a" ext_tax_ids="10116///10116" ext_tax_names="Rattus norvegicus///Rattus norvegicus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag>-II levels in <sd-tag id="sdTag380" source="sdapi" category="entity" entity_type="organism" role="component" text="rat" ext_ids="10116" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Rattus norvegicus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">rat</sd-tag> <sd-tag id="sdTag4" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="primary cortical neurons" ext_ids="CL:0002609" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron of cerebral cortex" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">primary cortical neurons</sd-tag> and decreased autophagosome synthesis in <sd-tag id="sdTag5" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="bafilomycin A1" ext_ids="CHEBI:22689" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bafilomycin A1" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">bafilomycin A<sub>1</sub></sd-tag>-treated <sd-tag id="sdTag381" source="sdapi" category="entity" entity_type="organism" role="component" text="rat" ext_ids="10116" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Rattus norvegicus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">rat</sd-tag> <sd-tag id="sdTag10" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="primary cortical neurons" ext_ids="CL:0002609" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron of cerebral cortex" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">primary cortical neurons</sd-tag> and <sd-tag id="sdTag6" source="sdapi" category="entity" entity_type="cell_line" role="experiment" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13375"/></sd-panel><sd-panel panel_id="13376"><p>(B-E) <sd-tag id="sdTag13" source="sdapi" category="assay" entity_type="" role="" text="Confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Confocal microscopy</sd-tag> images and analysis of autophagic flux by automated <sd-tag id="sdTag14" source="sdapi" category="assay" entity_type="" role="" text="Cellomics microscopy" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Cellomics microscopy</sd-tag> show that NO donors reduced <sd-tag id="sdTag15" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="autolysosome" ext_ids="GO:0044754" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="autolysosome" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">autolysosome</sd-tag> numbers in <sd-tag id="sdTag16" source="sdapi" category="entity" entity_type="protein" role="reporter" text="mRFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">mRFP</sd-tag>-<sd-tag id="sdTag17" source="sdapi" category="entity" entity_type="protein" role="reporter" text="GFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">GFP</sd-tag>-<sd-tag id="sdTag23" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q9BXW4///Q9H492///Q9GZQ8" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="MAP1LC3C///MAP1LC3A///MAP1LC3B" ext_tax_ids="9606///9606///9606" ext_tax_names="Homo sapiens///Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> <sd-tag id="sdTag24" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells grown in full medium (FM) (B and D) or starved with <sd-tag id="sdTag18" source="sdapi" category="entity" entity_type="undefined" role="component" text="HBSS" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">HBSS</sd-tag> (C and E). Cells in <sd-tag id="sdTag25" source="sdapi" category="entity" entity_type="undefined" role="component" text="HBSS" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">HBSS</sd-tag> had more <sd-tag id="sdTag20" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="autolysosomes" ext_ids="GO:0044754" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="autolysosome" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">autolysosomes</sd-tag> compared to FM (C). <sd-tag id="sdTag21" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="Autolysosome" ext_ids="GO:0044754" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="autolysosome" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">Autolysosome</sd-tag> number in untreated cells in FM is set at 100%.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13376"/></sd-panel><sd-panel panel_id="13377"><span>(F) NO donors increased <sd-tag id="sdTag30" source="sdapi" category="entity" entity_type="protein" role="reporter" text="EGFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">EGFP</sd-tag>-<sd-tag id="sdTag31" source="sdapi" category="entity" entity_type="protein" role="assayed" text="HD" ext_ids="P42859" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Htt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">HD</sd-tag>Q74 aggregates in a dose-dependent manner in <sd-tag id="sdTag36" source="sdapi" category="entity" entity_type="protein" role="reporter" text="EGFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">EGFP</sd-tag>-<sd-tag id="sdTag32" source="sdapi" category="entity" entity_type="protein" role="assayed" text="HD" ext_ids="P42859" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Htt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">HD</sd-tag>Q74-transfected <sd-tag id="sdTag33" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Atg5" ext_ids="11793" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Atg5" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Atg5</sd-tag></span><sup>+/+</sup><span>, but not in <sd-tag id="sdTag37" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Atg5" ext_ids="11793" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Atg5" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Atg5</sd-tag></span><sup>−/−</sup><span>, <sd-tag id="sdTag34" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>. <sd-tag id="sdTag38" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Atg5" ext_ids="11793" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Atg5" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Atg5</sd-tag></span><sup>−/−</sup> <span><sd-tag id="sdTag39" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag> had more <sd-tag id="sdTag40" source="sdapi" category="entity" entity_type="protein" role="reporter" text="EGFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">EGFP</sd-tag>-<sd-tag id="sdTag35" source="sdapi" category="entity" entity_type="gene" role="component" text="HD" ext_ids="15194" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Htt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">HD</sd-tag>Q74 aggregates than <sd-tag id="sdTag41" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Atg5" ext_ids="11793" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Atg5" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Atg5</sd-tag></span><sup>+/+</sup> <span><sd-tag id="sdTag42" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>.</span><graphic href="https://api.sourcedata.io/file.php?panel_id=13377"/></sd-panel><sd-panel panel_id="13378"><p>(G and H) <sd-tag id="sdTag50" source="sdapi" category="assay" entity_type="" role="" text="Confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Confocal microscopy</sd-tag> images (H) and <sd-tag id="sdTag48" source="sdapi" category="assay" entity_type="" role="" text="immunofluorescence" ext_ids="BAO_0000450" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="fluorescence microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunofluorescence</sd-tag> analysis with anti-<sd-tag id="sdTag49" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Atg16" ext_ids="Q8NAA4///Q676U5" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="ATG16L2///ATG16L1" ext_tax_ids="9606///9606" ext_tax_names="Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">Atg16</sd-tag> antibody (G) show that NO donors reduced the percentage of <sd-tag id="sdTag51" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells with <sd-tag id="sdTag52" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Atg16" ext_ids="Q8NAA4///Q676U5" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="ATG16L2///ATG16L1" ext_tax_ids="9606///9606" ext_tax_names="Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">Atg16</sd-tag>-positive structures (arrows) under starvation. Graphical data denote mean ± SEM.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13378"/></sd-panel></fig><fig id="4353"><title></title><label>Figure 2</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4353"/><sd-panel panel_id="13379"><p>(A) NO donors reduced <sd-tag id="sdTag55" source="sdapi" category="entity" entity_type="protein" role="assayed" text="JNK1" ext_ids="P45983" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="MAPK8" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">JNK1</sd-tag> phosphorylation in <sd-tag id="sdTag58" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells, as analyzed by <sd-tag id="sdTag56" source="sdapi" category="assay" entity_type="" role="" text="immunoprecipitation" ext_ids="BAO_0002508" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="immunoprecipitation" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoprecipitation</sd-tag> with anti-<sd-tag id="sdTag59" source="sdapi" category="entity" entity_type="protein" role="assayed" text="JNK1" ext_ids="P45983" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="MAPK8" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">JNK1</sd-tag> agarose-conjugated beads and <sd-tag id="sdTag57" source="sdapi" category="assay" entity_type="" role="" text="immunoblotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoblotting</sd-tag> with anti-phospho-<sd-tag id="sdTag60" source="sdapi" category="entity" entity_type="protein" role="assayed" text="JNK" ext_ids="P53779///P45984///P45983" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="MAPK10///MAPK9///MAPK8" ext_tax_ids="9606///9606///9606" ext_tax_names="Homo sapiens///Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">JNK</sd-tag> antibody.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13379"/></sd-panel><sd-panel panel_id="13380"><p>(B) NO donors reduced <sd-tag id="sdTag63" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Bcl-2" ext_ids="P10415" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Bcl-2</sd-tag> phosphorylation in <sd-tag id="sdTag64" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells, as analyzed by <sd-tag id="sdTag65" source="sdapi" category="assay" entity_type="" role="" text="immunoblotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoblotting</sd-tag> with anti-phospho-<sd-tag id="sdTag66" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Bcl-2" ext_ids="P10415" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Bcl-2</sd-tag> antibody.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13380"/></sd-panel><sd-panel panel_id="13381"><p>C) <sd-tag id="sdTag71" source="sdapi" category="assay" entity_type="" role="" text="Immunoblot" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoblot</sd-tag> analysis with anti-phospho-<sd-tag id="sdTag72" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Bcl-2" ext_ids="P10415" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Bcl-2</sd-tag> antibody shows that <sd-tag id="sdTag69" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="DETA NONOate" ext_ids="CHEBI:50154" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="1,1-bis(2-aminoethyl)-2-hydroxy-3-oxotriazane" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DETA NONOate</sd-tag> could not reduce phospho-<sd-tag id="sdTag73" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Bcl-2" ext_ids="P10415" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Bcl-2</sd-tag> in <sd-tag id="sdTag70" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag>-CA <sd-tag id="sdTag74" source="sdapi" category="entity" entity_type="protein" role="assayed" text="JNK1" ext_ids="P45983" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="MAPK8" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">JNK1</sd-tag>-transfected <sd-tag id="sdTag75" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells, where phospho-<sd-tag id="sdTag76" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Bcl-2" ext_ids="P10415" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Bcl-2</sd-tag> was higher compared to mock-transfected cells.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13381"/></sd-panel><sd-panel panel_id="13382"><p>(D and E) <sd-tag id="sdTag78" source="sdapi" category="assay" entity_type="" role="" text="Immunoprecipitation" ext_ids="BAO_0002508" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="immunoprecipitation" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoprecipitation</sd-tag> with anti-<sd-tag id="sdTag82" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag> M2 affinity agarose gel and <sd-tag id="sdTag83" source="sdapi" category="assay" entity_type="" role="" text="immunoblotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoblotting</sd-tag> with anti-<sd-tag id="sdTag79" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Myc" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Myc</sd-tag> antibody shows that NO donors increased the interaction of <sd-tag id="sdTag84" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag>-<sd-tag id="sdTag80" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Beclin 1" ext_ids="Q14457" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BECN1" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Beclin 1</sd-tag> with WT <sd-tag id="sdTag85" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Myc" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Myc</sd-tag>-<sd-tag id="sdTag81" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="596" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> (D), but not with AAA <sd-tag id="sdTag86" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Myc" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Myc</sd-tag>-<sd-tag id="sdTag87" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Bcl-2" ext_ids="P10415" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Bcl-2</sd-tag> (E), in <sd-tag id="sdTag88" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells transfected with WT <sd-tag id="sdTag89" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Myc" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Myc</sd-tag>-<sd-tag id="sdTag90" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Bcl-2" ext_ids="P10415" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Bcl-2</sd-tag> (D) or AAA <sd-tag id="sdTag91" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Myc" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Myc</sd-tag>-<sd-tag id="sdTag92" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Bcl-2" ext_ids="P10415" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Bcl-2</sd-tag> (E) along with either empty <sd-tag id="sdTag93" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag> or <sd-tag id="sdTag94" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag>-<sd-tag id="sdTag95" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Beclin 1" ext_ids="8678" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="BECN1" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Beclin 1</sd-tag>. Asterisk denotes IgG band (E).</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13382"/></sd-panel><sd-panel panel_id="13383"><p>(F) <sd-tag id="sdTag100" source="sdapi" category="assay" entity_type="" role="" text="Immunoprecipitation" ext_ids="BAO_0002508" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="immunoprecipitation" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoprecipitation</sd-tag> with anti-<sd-tag id="sdTag101" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag> M2 affinity agarose gel and <sd-tag id="sdTag102" source="sdapi" category="assay" entity_type="" role="" text="immunoblotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoblotting</sd-tag> with anti-<sd-tag id="sdTag98" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Vps34" ext_ids="Q8NEB9" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="PIK3C3" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Vps34</sd-tag> antibody shows that NO donors decreased <sd-tag id="sdTag103" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag>-<sd-tag id="sdTag104" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Beclin 1" ext_ids="Q14457" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BECN1" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Beclin 1</sd-tag>-<sd-tag id="sdTag99" source="sdapi" category="entity" entity_type="protein" role="assayed" text="hVps34" ext_ids="Q8NEB9" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="PIK3C3" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">hVps34</sd-tag> interaction in <sd-tag id="sdTag105" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells transfected with <sd-tag id="sdTag106" source="sdapi" category="entity" entity_type="protein" role="assayed" text="hVps34" ext_ids="Q8NEB9" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="PIK3C3" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">hVps34</sd-tag> along with either empty <sd-tag id="sdTag107" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag> or <sd-tag id="sdTag108" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag>-<sd-tag id="sdTag109" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Beclin 1" ext_ids="8678" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="BECN1" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Beclin 1</sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13383"/></sd-panel><sd-panel panel_id="13384"><p>(G) <sd-tag id="sdTag114" source="sdapi" category="assay" entity_type="" role="" text="Immunoprecipitation" ext_ids="BAO_0002508" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="immunoprecipitation" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoprecipitation</sd-tag> with anti-<sd-tag id="sdTag115" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag> M2 affinity agarose gel and <sd-tag id="sdTag116" source="sdapi" category="assay" entity_type="" role="" text="immunoblotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoblotting</sd-tag> with anti-<sd-tag id="sdTag117" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Vps34" ext_ids="Q8NEB9" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="PIK3C3" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Vps34</sd-tag> antibody shows that AAA <sd-tag id="sdTag118" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Myc" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Myc</sd-tag>-<sd-tag id="sdTag112" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="596" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> decreased <sd-tag id="sdTag119" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag>-<sd-tag id="sdTag120" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Beclin 1" ext_ids="Q14457" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BECN1" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Beclin 1</sd-tag>-<sd-tag id="sdTag121" source="sdapi" category="entity" entity_type="protein" role="assayed" text="hVps34" ext_ids="Q8NEB9" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="PIK3C3" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">hVps34</sd-tag> interaction in the presence (right panel) or absence (left panel) of <sd-tag id="sdTag122" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="DETA NONOate" ext_ids="CHEBI:50154" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="1,1-bis(2-aminoethyl)-2-hydroxy-3-oxotriazane" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DETA NONOate</sd-tag> in <sd-tag id="sdTag124" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells transfected with <sd-tag id="sdTag126" source="sdapi" category="entity" entity_type="protein" role="assayed" text="hVps34" ext_ids="Q8NEB9" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="PIK3C3" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">hVps34</sd-tag> along with either empty <sd-tag id="sdTag128" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag> or <sd-tag id="sdTag130" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Flag" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Flag</sd-tag>-<sd-tag id="sdTag113" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Beclin 1" ext_ids="8678" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="BECN1" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Beclin 1</sd-tag>, and with pcDNA3.1 or AAA <sd-tag id="sdTag132" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Myc" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Myc</sd-tag>-<sd-tag id="sdTag133" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Bcl-2" ext_ids="P10415" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Bcl-2</sd-tag>. Graphical data denote mean ± SEM.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13384"/></sd-panel></fig><fig id="4354"><title></title><label>Figure 3</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4354"/><sd-panel panel_id="13385"><p>(A) <sd-tag id="sdTag135" source="sdapi" category="assay" entity_type="" role="" text="Immunoblot" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoblot</sd-tag> analysis with anti-<sd-tag id="sdTag136" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q9CQV6///Q91VR7" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3b///Map1lc3a" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> antibody shows that <sd-tag id="sdTag137" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="DETA NONOate" ext_ids="CHEBI:50154" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="1,1-bis(2-aminoethyl)-2-hydroxy-3-oxotriazane" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DETA NONOate</sd-tag> reduced autophagosome synthesis in <sd-tag id="sdTag134" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="bafilomycin A1" ext_ids="CHEBI:22689" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bafilomycin A1" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">bafilomycin A<sub>1</sub></sd-tag>-treated WT <sd-tag id="sdTag138" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="596" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> and AAA <sd-tag id="sdTag139" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="596" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> <sd-tag id="sdTag140" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13385"/></sd-panel><sd-panel panel_id="13386"><p>(B and C) NO donors decreased <sd-tag id="sdTag146" source="sdapi" category="entity" entity_type="protein" role="reporter" text="EGFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">EGFP</sd-tag>-<sd-tag id="sdTag147" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q9CQV6///Q91VR7" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3b///Map1lc3a" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> vesicles in <sd-tag id="sdTag148" source="sdapi" category="entity" entity_type="protein" role="reporter" text="EGFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">EGFP</sd-tag>-<sd-tag id="sdTag149" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q9CQV6///Q91VR7" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3b///Map1lc3a" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag>-transfected WT <sd-tag id="sdTag142" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="12043" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Bcl2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> and AAA <sd-tag id="sdTag143" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="12043" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Bcl2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> <sd-tag id="sdTag150" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag> (C). Images were acquired by a <sd-tag id="sdTag144" source="sdapi" category="assay" entity_type="" role="" text="confocal microscope" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">confocal microscope</sd-tag> (B). WT <sd-tag id="sdTag145" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="12043" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Bcl2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> and AAA <sd-tag id="sdTag151" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="12043" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Bcl2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> <sd-tag id="sdTag152" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag> were analyzed separately.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13386"/></sd-panel><sd-panel panel_id="13387"><p>(D) NO donors increased <sd-tag id="sdTag157" source="sdapi" category="entity" entity_type="protein" role="reporter" text="EGFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">EGFP</sd-tag>-<sd-tag id="sdTag155" source="sdapi" category="entity" entity_type="gene" role="component" text="HD" ext_ids="15194" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Htt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">HD</sd-tag>Q74 aggregates in <sd-tag id="sdTag158" source="sdapi" category="entity" entity_type="protein" role="reporter" text="EGFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">EGFP</sd-tag>-<sd-tag id="sdTag156" source="sdapi" category="entity" entity_type="protein" role="assayed" text="HD" ext_ids="P42859" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Htt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">HD</sd-tag>Q74-transfected WT <sd-tag id="sdTag159" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="12043" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Bcl2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> and AAA <sd-tag id="sdTag160" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="12043" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Bcl2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> <sd-tag id="sdTag161" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>. WT <sd-tag id="sdTag162" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="12043" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Bcl2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> and AAA <sd-tag id="sdTag163" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="12043" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Bcl2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> <sd-tag id="sdTag164" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag> were analyzed separately.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13387"/></sd-panel><sd-panel panel_id="13388"><p>(E) <sd-tag id="sdTag171" source="sdapi" category="assay" entity_type="" role="" text="Immunoblot" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoblot</sd-tag> analysis with anti-<sd-tag id="sdTag172" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q91VR7///Q9CQV6" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3a///Map1lc3b" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> antibody shows that <sd-tag id="sdTag173" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="DETA NONOate" ext_ids="CHEBI:50154" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="1,1-bis(2-aminoethyl)-2-hydroxy-3-oxotriazane" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DETA NONOate</sd-tag> reduced autophagosome synthesis in <sd-tag id="sdTag168" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="bafilomycin A1" ext_ids="CHEBI:22689" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bafilomycin A1" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">bafilomycin A<sub>1</sub></sd-tag>-treated WT Jnk, <sd-tag id="sdTag169" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Jnk1" ext_ids="26419" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Mapk8" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Jnk1</sd-tag><sup>−/−</sup>, and <sd-tag id="sdTag170" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Jnk2" ext_ids="26420" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Mapk9" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Jnk2</sd-tag><sup>−/−</sup> <sd-tag id="sdTag174" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13388"/></sd-panel><sd-panel panel_id="13389"><p>(F) <sd-tag id="sdTag179" source="sdapi" category="assay" entity_type="" role="" text="Immunoblot" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoblot</sd-tag> analyses with anti-phospho-<sd-tag id="sdTag176" source="sdapi" category="entity" entity_type="protein" role="assayed" text="S6K" ext_ids="Q15418///P23443///Q96S38" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="RPS6KA1///RPS6KB1///RPS6KC1" ext_tax_ids="9606///9606///9606" ext_tax_names="Homo sapiens///Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">S6K</sd-tag> and anti-phospho-<sd-tag id="sdTag177" source="sdapi" category="entity" entity_type="protein" role="assayed" text="S6" ext_ids="P62753" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="RPS6" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">S6</sd-tag> antibodies show that NO donors activated <sd-tag id="sdTag178" source="sdapi" category="entity" entity_type="subcellular" role="component" text="mTORC1" ext_ids="GO:0031931" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="TORC1 complex" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">mTORC1</sd-tag> in <sd-tag id="sdTag180" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13389"/></sd-panel><sd-panel panel_id="13390"><p>(G) <sd-tag id="sdTag183" source="sdapi" category="assay" entity_type="" role="" text="Confocal microscope" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Confocal microscope</sd-tag> images of <sd-tag id="sdTag184" source="sdapi" category="assay" entity_type="" role="" text="immunofluorescence" ext_ids="BAO_0000450" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="fluorescence microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunofluorescence</sd-tag> with anti-phospho-<sd-tag id="sdTag185" source="sdapi" category="entity" entity_type="protein" role="assayed" text="S6" ext_ids="P62753" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="RPS6" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">S6</sd-tag> antibody show that <sd-tag id="sdTag186" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="DETA NONOate" ext_ids="CHEBI:50154" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="1,1-bis(2-aminoethyl)-2-hydroxy-3-oxotriazane" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DETA NONOate</sd-tag> increased <sd-tag id="sdTag187" source="sdapi" category="entity" entity_type="protein" role="assayed" text="S6" ext_ids="P62753" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="RPS6" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">S6</sd-tag> phosphorylation; arrowhead shows a cell where this effect was not observed.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13390"/></sd-panel><sd-panel panel_id="13391"><p>(H) <sd-tag id="sdTag190" source="sdapi" category="assay" entity_type="" role="" text="Immunoblot" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoblot</sd-tag> analyses with anti-phospho-<sd-tag id="sdTag191" source="sdapi" category="entity" entity_type="protein" role="assayed" text="S6K" ext_ids="P18653///Q8BLK9///Q8BSK8" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="Rps6ka1///Rps6kc1///Rps6kb1" ext_tax_ids="10090///10090///10090" ext_tax_names="Mus musculus///Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">S6K</sd-tag> and anti-phospho-<sd-tag id="sdTag192" source="sdapi" category="entity" entity_type="protein" role="assayed" text="S6" ext_ids="P62754" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Rps6" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">S6</sd-tag> antibodies show that NO donors activated <sd-tag id="sdTag193" source="sdapi" category="entity" entity_type="subcellular" role="component" text="mTORC1" ext_ids="GO:0031931" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="TORC1 complex" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">mTORC1</sd-tag> in WT <sd-tag id="sdTag189" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="12043" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Bcl2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> and AAA <sd-tag id="sdTag194" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="12043" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Bcl2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> <sd-tag id="sdTag195" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13391"/></sd-panel><sd-panel panel_id="13392"><p>(I) <sd-tag id="sdTag201" source="sdapi" category="assay" entity_type="" role="" text="Confocal microscope" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Confocal microscope</sd-tag> images of <sd-tag id="sdTag202" source="sdapi" category="assay" entity_type="" role="" text="immunofluorescence" ext_ids="BAO_0000450" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="fluorescence microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunofluorescence</sd-tag> with anti-phospho-<sd-tag id="sdTag198" source="sdapi" category="entity" entity_type="protein" role="assayed" text="mTOR" ext_ids="Q9JLN9" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Mtor" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">mTOR</sd-tag> and anti-<sd-tag id="sdTag199" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LAMP1" ext_ids="P11438" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Lamp1" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">LAMP1</sd-tag> antibodies in <sd-tag id="sdTag203" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells show that <sd-tag id="sdTag204" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="DETA NONOate" ext_ids="CHEBI:50154" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="1,1-bis(2-aminoethyl)-2-hydroxy-3-oxotriazane" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DETA NONOate</sd-tag> increased phospho-<sd-tag id="sdTag205" source="sdapi" category="entity" entity_type="protein" role="assayed" text="mTOR" ext_ids="Q9JLN9" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Mtor" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">mTOR</sd-tag> but did not alter its distribution with <sd-tag id="sdTag200" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="lysosomes" ext_ids="GO:0005764" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="lysosome" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">lysosomes</sd-tag>. Graphical data denote mean ± SEM.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13392"/></sd-panel></fig><fig id="4355"><title></title><label>Figure 4</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4355"/><sd-panel panel_id="13393"><p>(A) <sd-tag id="sdTag209" source="sdapi" category="assay" entity_type="" role="" text="Immunoblot" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoblot</sd-tag> analyses with anti-phospho-<sd-tag id="sdTag210" source="sdapi" category="entity" entity_type="protein" role="assayed" text="S6K" ext_ids="P18653///Q8BLK9///Q8BSK8" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="Rps6ka1///Rps6kc1///Rps6kb1" ext_tax_ids="10090///10090///10090" ext_tax_names="Mus musculus///Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">S6K</sd-tag> and anti-phospho-<sd-tag id="sdTag211" source="sdapi" category="entity" entity_type="protein" role="assayed" text="S6" ext_ids="P62754" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Rps6" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">S6</sd-tag> antibodies show that NO donors activated <sd-tag id="sdTag212" source="sdapi" category="entity" entity_type="subcellular" role="component" text="mTORC1" ext_ids="GO:0031931" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="TORC1 complex" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">mTORC1</sd-tag> in <sd-tag id="sdTag208" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Tsc2" ext_ids="22084" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Tsc2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Tsc2</sd-tag><sup>+/+</sup> <sd-tag id="sdTag213" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>, but not in <sd-tag id="sdTag214" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Tsc2" ext_ids="22084" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Tsc2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Tsc2</sd-tag><sup>−/−</sup>, <sd-tag id="sdTag215" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13393"/></sd-panel><sd-panel panel_id="13394"><p>(B) NO donors reduced phosphorylation of <sd-tag id="sdTag218" source="sdapi" category="entity" entity_type="protein" role="assayed" text="IKKα" ext_ids="Q60680" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Chuk" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">IKKα</sd-tag>/β and <sd-tag id="sdTag220" source="sdapi" category="entity" entity_type="protein" role="assayed" text="AMPKα" ext_ids="Q8BRK8///Q5EG47" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Prkaa2///Prkaa1" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">AMPKα</sd-tag> in <sd-tag id="sdTag221" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>, as analyzed by <sd-tag id="sdTag222" source="sdapi" category="assay" entity_type="" role="" text="immunoblotting" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoblotting</sd-tag> with anti-phospho-<sd-tag id="sdTag223" source="sdapi" category="entity" entity_type="protein" role="assayed" text="IKKα" ext_ids="Q60680" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Chuk" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">IKKα</sd-tag>/β and anti-phospho-<sd-tag id="sdTag224" source="sdapi" category="entity" entity_type="protein" role="assayed" text="AMPKα" ext_ids="Q8BRK8///Q5EG47" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Prkaa2///Prkaa1" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">AMPKα</sd-tag> antibodies, respectively.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13394"/></sd-panel><sd-panel panel_id="13395"><p>(C) <sd-tag id="sdTag228" source="sdapi" category="assay" entity_type="" role="" text="Immunoblot" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoblot</sd-tag> analyses with anti-phospho-<sd-tag id="sdTag229" source="sdapi" category="entity" entity_type="protein" role="experiment" text="S6K" ext_ids="P18653///Q8BLK9///Q8BSK8" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="Rps6ka1///Rps6kc1///Rps6kb1" ext_tax_ids="10090///10090///10090" ext_tax_names="Mus musculus///Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">S6K</sd-tag> and anti-phospho-<sd-tag id="sdTag230" source="sdapi" category="entity" entity_type="protein" role="assayed" text="S6" ext_ids="P62754" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Rps6" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">S6</sd-tag> antibodies show that NO donors activated <sd-tag id="sdTag231" source="sdapi" category="entity" entity_type="subcellular" role="component" text="mTORC1" ext_ids="GO:0031931" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="TORC1 complex" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">mTORC1</sd-tag> in <sd-tag id="sdTag227" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Ikkβ" ext_ids="16150" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Ikbkb" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Ikkβ</sd-tag><sup>+/+</sup> <sd-tag id="sdTag232" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>, but not in <sd-tag id="sdTag233" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Ikkβ" ext_ids="16150" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Ikbkb" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Ikkβ</sd-tag><sup>−/−</sup> <sd-tag id="sdTag234" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13395"/></sd-panel><sd-panel panel_id="13396"><p>(D) <sd-tag id="sdTag238" source="sdapi" category="assay" entity_type="" role="" text="Immunoblot" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoblot</sd-tag> analysis with anti-<sd-tag id="sdTag239" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q91VR7///Q9CQV6" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3a///Map1lc3b" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> antibody shows that <sd-tag id="sdTag240" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="DETA NONOate" ext_ids="CHEBI:50154" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="1,1-bis(2-aminoethyl)-2-hydroxy-3-oxotriazane" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DETA NONOate</sd-tag> reduced autophagosome synthesis in <sd-tag id="sdTag237" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="bafilomycin A1" ext_ids="CHEBI:22689" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bafilomycin A1" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">bafilomycin A<sub>1</sub></sd-tag>-treated <sd-tag id="sdTag241" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Tsc2" ext_ids="22084" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Tsc2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Tsc2</sd-tag><sup>+/+</sup> and <sd-tag id="sdTag242" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Tsc2" ext_ids="22084" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Tsc2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Tsc2</sd-tag><sup>−/−</sup> <sd-tag id="sdTag243" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13396"/></sd-panel><sd-panel panel_id="13397"><p>(E) <sd-tag id="sdTag246" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="DETA NONOate" ext_ids="CHEBI:50154" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="1,1-bis(2-aminoethyl)-2-hydroxy-3-oxotriazane" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DETA NONOate</sd-tag> decreased <sd-tag id="sdTag247" source="sdapi" category="entity" entity_type="protein" role="reporter" text="EGFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">EGFP</sd-tag>-<sd-tag id="sdTag248" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q9CQV6///Q91VR7" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3b///Map1lc3a" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> vesicles in <sd-tag id="sdTag249" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Tsc2" ext_ids="22084" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Tsc2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Tsc2</sd-tag><sup>+/+</sup> and <sd-tag id="sdTag250" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Tsc2" ext_ids="22084" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Tsc2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Tsc2</sd-tag><sup>−/−</sup><sd-tag id="sdTag251" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag> transfected with <sd-tag id="sdTag252" source="sdapi" category="entity" entity_type="protein" role="reporter" text="EGFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">EGFP</sd-tag>-<sd-tag id="sdTag253" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q91VR7///Q9CQV6" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3a///Map1lc3b" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag>, along with either pcDNA3.1 or AAA <sd-tag id="sdTag254" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Myc" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Myc</sd-tag>-<sd-tag id="sdTag255" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="12043" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Bcl2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag>. Although it further reduced <sd-tag id="sdTag256" source="sdapi" category="entity" entity_type="protein" role="reporter" text="EGFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">EGFP</sd-tag>-<sd-tag id="sdTag257" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q91VR7///Q9CQV6" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3a///Map1lc3b" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> vesicles in <sd-tag id="sdTag258" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Tsc2" ext_ids="22084" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Tsc2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Tsc2</sd-tag><sup>+/+</sup><sd-tag id="sdTag259" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag> expressing AAA <sd-tag id="sdTag260" source="sdapi" category="entity" entity_type="protein" role="reporter" text="Myc" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Myc</sd-tag>-<sd-tag id="sdTag245" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Bcl-2" ext_ids="12043" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Bcl2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Bcl-2</sd-tag> compared to mock-transfected <sd-tag id="sdTag261" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Tsc2" ext_ids="22084" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Tsc2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Tsc2</sd-tag><sup>+/+</sup><sd-tag id="sdTag262" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>, this effect was not seen in <sd-tag id="sdTag263" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Tsc2" ext_ids="22084" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Tsc2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Tsc2</sd-tag><sup>−/−</sup><sd-tag id="sdTag264" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>. <sd-tag id="sdTag265" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Tsc2" ext_ids="22084" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Tsc2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Tsc2</sd-tag><sup>+/+</sup> and <sd-tag id="sdTag266" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Tsc2" ext_ids="22084" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Tsc2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Tsc2</sd-tag><sup>−/−</sup><sd-tag id="sdTag267" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag> were analyzed separately. Graphical data denote mean ± SEM.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13397"/></sd-panel></fig><fig id="4356"><title></title><label>Figure 5</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4356"/><sd-panel panel_id="13398"><p>(A-D) <sd-tag id="sdTag277" source="sdapi" category="assay" entity_type="" role="" text="Immunoblot" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoblot</sd-tag> analyses with anti-<sd-tag id="sdTag278" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q9BXW4///Q9H492///Q9GZQ8" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="MAP1LC3C///MAP1LC3A///MAP1LC3B" ext_tax_ids="9606///9606///9606" ext_tax_names="Homo sapiens///Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag>, along with anti-<sd-tag id="sdTag269" source="sdapi" category="entity" entity_type="gene" role="intervention" text="nNOS" ext_ids="4842" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="NOS1" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">nNOS</sd-tag>, anti-<sd-tag id="sdTag270" source="sdapi" category="entity" entity_type="gene" role="intervention" text="iNOS" ext_ids="4843" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="NOS2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">iNOS</sd-tag>, and anti-<sd-tag id="sdTag271" source="sdapi" category="entity" entity_type="gene" role="intervention" text="eNOS" ext_ids="4846" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="NOS3" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">eNOS</sd-tag> antibodies, show decreased <sd-tag id="sdTag279" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q9BXW4///Q9H492///Q9GZQ8" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="MAP1LC3C///MAP1LC3A///MAP1LC3B" ext_tax_ids="9606///9606///9606" ext_tax_names="Homo sapiens///Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag>-II levels in stable <sd-tag id="sdTag272" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HEK293" ext_ids="CVCL_0045" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HEK293" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HEK293</sd-tag> cell lines overexpressing <sd-tag id="sdTag273" source="sdapi" category="entity" entity_type="protein" role="assayed" text="nNOS" ext_ids="P29475" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="NOS1" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">nNOS</sd-tag> (A and D), <sd-tag id="sdTag274" source="sdapi" category="entity" entity_type="protein" role="assayed" text="iNOS" ext_ids="P35228" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="NOS2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">iNOS</sd-tag>-<sd-tag id="sdTag280" source="sdapi" category="entity" entity_type="protein" role="reporter" text="GFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">GFP</sd-tag> (B and D), or <sd-tag id="sdTag275" source="sdapi" category="entity" entity_type="protein" role="assayed" text="eNOS" ext_ids="P29474" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="NOS3" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">eNOS</sd-tag> (C and D) compared to <sd-tag id="sdTag281" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HEK293" ext_ids="CVCL_0045" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HEK293" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HEK293</sd-tag> control cells in the presence or absence of <sd-tag id="sdTag276" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="bafilomycin A1" ext_ids="CHEBI:22689" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bafilomycin A1" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">bafilomycin A<sub>1</sub></sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13398"/></sd-panel><sd-panel panel_id="13399"><p>(E and F) <sd-tag id="sdTag283" source="sdapi" category="entity" entity_type="protein" role="reporter" text="mCherry" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">mCherry</sd-tag>-<sd-tag id="sdTag379" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q9GZQ8///Q9BXW4///Q9H492" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="MAP1LC3B///MAP1LC3C///MAP1LC3A" ext_tax_ids="9606///9606///9606" ext_tax_names="Homo sapiens///Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> vesicles were reduced in <sd-tag id="sdTag286" source="sdapi" category="entity" entity_type="protein" role="reporter" text="mCherry" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">mCherry</sd-tag>-<sd-tag id="sdTag287" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q9GZQ8///Q9BXW4///Q9H492" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="MAP1LC3B///MAP1LC3C///MAP1LC3A" ext_tax_ids="9606///9606///9606" ext_tax_names="Homo sapiens///Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag>-transfected stable <sd-tag id="sdTag288" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HEK293" ext_ids="CVCL_0045" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HEK293" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HEK293</sd-tag> NOS cell lines compared to <sd-tag id="sdTag289" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HEK293" ext_ids="CVCL_0045" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HEK293" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HEK293</sd-tag> control cells cultured in <sd-tag id="sdTag290" source="sdapi" category="entity" entity_type="undefined" role="component" text="HBSS" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">HBSS</sd-tag>, an effect that was restored in the NOS cells by <sd-tag id="sdTag284" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="L-NAME" ext_ids="CHEBI:7549" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="N(gamma)-nitro-L-arginine methyl ester" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">L-NAME</sd-tag> (F). Images were acquired by a <sd-tag id="sdTag291" source="sdapi" category="assay" entity_type="" role="" text="confocal microscope" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">confocal microscope</sd-tag> (E).</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13399"/></sd-panel><sd-panel panel_id="13400"><p>(G and H) <sd-tag id="sdTag296" source="sdapi" category="assay" entity_type="" role="" text="Confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Confocal microscopy</sd-tag> images (G) and <sd-tag id="sdTag297" source="sdapi" category="assay" entity_type="" role="" text="immunofluorescence" ext_ids="BAO_0000450" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="fluorescence microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunofluorescence</sd-tag> analysis with anti-<sd-tag id="sdTag298" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Atg16" ext_ids="Q676U5///Q8NAA4" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="ATG16L1///ATG16L2" ext_tax_ids="9606///9606" ext_tax_names="Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">Atg16</sd-tag> antibody show that stable <sd-tag id="sdTag299" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HEK293" ext_ids="CVCL_0045" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HEK293" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HEK293</sd-tag> NOS cell lines had fewer <sd-tag id="sdTag300" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Atg16" ext_ids="Q8NAA4///Q676U5" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="ATG16L2///ATG16L1" ext_tax_ids="9606///9606" ext_tax_names="Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">Atg16</sd-tag>-positive structures under starvation, compared to <sd-tag id="sdTag301" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HEK293" ext_ids="CVCL_0045" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HEK293" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HEK293</sd-tag> control cells (H). Graphical data denote mean ± SEM.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13400"/></sd-panel></fig><fig id="4357"><title></title><label>Figure 6</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4357"/><sd-panel panel_id="13401"><p>(A-F) <sd-tag id="sdTag306" source="sdapi" category="assay" entity_type="" role="" text="Immunoblot" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoblot</sd-tag> analyses with anti-<sd-tag id="sdTag307" source="sdapi" category="entity" entity_type="protein" role="assayed" text="nNOS" ext_ids="P29475" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="NOS1" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">nNOS</sd-tag>, anti-<sd-tag id="sdTag308" source="sdapi" category="entity" entity_type="gene" role="intervention" text="iNOS" ext_ids="4843" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="NOS2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">iNOS</sd-tag>, anti-<sd-tag id="sdTag309" source="sdapi" category="entity" entity_type="protein" role="assayed" text="eNOS" ext_ids="P29474" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="NOS3" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">eNOS</sd-tag>, anti-phospho-<sd-tag id="sdTag310" source="sdapi" category="entity" entity_type="protein" role="assayed" text="JNK1" ext_ids="P45983" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="MAPK8" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">JNK1</sd-tag>, anti-phospho-<sd-tag id="sdTag311" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Bcl-2" ext_ids="P10415" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Bcl-2</sd-tag>, anti-phospho-<sd-tag id="sdTag312" source="sdapi" category="entity" entity_type="protein" role="assayed" text="S6K" ext_ids="P23443///Q96S38///Q15418" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="RPS6KB1///RPS6KC1///RPS6KA1" ext_tax_ids="9606///9606///9606" ext_tax_names="Homo sapiens///Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">S6K</sd-tag>, and anti-phospho-<sd-tag id="sdTag313" source="sdapi" category="entity" entity_type="protein" role="assayed" text="S6" ext_ids="P62753" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="RPS6" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">S6</sd-tag> antibodies show that stable <sd-tag id="sdTag314" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HEK293" ext_ids="CVCL_0045" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HEK293" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HEK293</sd-tag> cell lines overexpressing <sd-tag id="sdTag315" source="sdapi" category="entity" entity_type="gene" role="intervention" text="nNOS" ext_ids="4842" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="NOS1" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">nNOS</sd-tag> (A and D), <sd-tag id="sdTag316" source="sdapi" category="entity" entity_type="protein" role="assayed" text="iNOS" ext_ids="P35228" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="NOS2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">iNOS</sd-tag>-<sd-tag id="sdTag317" source="sdapi" category="entity" entity_type="protein" role="reporter" text="GFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">GFP</sd-tag> (B and E), or <sd-tag id="sdTag318" source="sdapi" category="entity" entity_type="gene" role="intervention" text="eNOS" ext_ids="4846" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="NOS3" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">eNOS</sd-tag> (C and F) inhibited both the <sd-tag id="sdTag319" source="sdapi" category="entity" entity_type="protein" role="assayed" text="JNK1" ext_ids="P45983" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="MAPK8" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">JNK1</sd-tag>-<sd-tag id="sdTag320" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Bcl-2" ext_ids="P10415" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BCL2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Bcl-2</sd-tag> and <sd-tag id="sdTag321" source="sdapi" category="entity" entity_type="subcellular" role="component" text="mTORC1" ext_ids="GO:0031931" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="TORC1 complex" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">mTORC1</sd-tag> pathways compared to the <sd-tag id="sdTag322" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HEK293" ext_ids="CVCL_0045" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HEK293" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HEK293</sd-tag> control cells under basal (FM) (A-C) or starvation (<sd-tag id="sdTag323" source="sdapi" category="entity" entity_type="undefined" role="component" text="HBSS" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">HBSS</sd-tag>) (D-F) conditions. Graphical data denote mean ± SEM.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13401"/></sd-panel></fig><fig id="4358"><title></title><label>Figure 7</label><graphic href="https://api.sourcedata.io/file.php?figure_id=4358"/><sd-panel panel_id="13402"><p>(A) <sd-tag id="sdTag331" source="sdapi" category="assay" entity_type="" role="" text="Immunoblot" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Immunoblot</sd-tag> analyses with anti-<sd-tag id="sdTag332" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q9GZQ8///Q9BXW4///Q9H492" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="MAP1LC3B///MAP1LC3C///MAP1LC3A" ext_tax_ids="9606///9606///9606" ext_tax_names="Homo sapiens///Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> antibody show that <sd-tag id="sdTag326" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="rapamycin" ext_ids="CHEBI:9168" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="sirolimus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">rapamycin</sd-tag> (<sd-tag id="sdTag327" source="sdapi" category="time" entity_type="" role="" text="8 hr" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">8 hr</sd-tag>) and <sd-tag id="sdTag333" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="L-NAME" ext_ids="CHEBI:7549" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="N(gamma)-nitro-L-arginine methyl ester" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">L-NAME</sd-tag> (<sd-tag id="sdTag328" source="sdapi" category="time" entity_type="" role="" text="24 hr" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">24 hr</sd-tag>) increased autophagosome synthesis in <sd-tag id="sdTag329" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="bafilomycin A1" ext_ids="CHEBI:22689" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bafilomycin A1" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">bafilomycin A<sub>1</sub></sd-tag>-treated <sd-tag id="sdTag330" source="sdapi" category="entity" entity_type="organism" role="component" text="mouse" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="mouse" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mouse</sd-tag> <sd-tag id="sdTag336" source="sdapi" category="entity" entity_type="cell_type" role="experiment" text="primary cortical neurons" ext_ids="CL:0002609" norm_text="" ext_dbs="CL" in_caption="True" ext_names="neuron of cerebral cortex" ext_tax_ids="" ext_tax_names="" ext_urls=" https://identifiers.org/">primary cortical neurons</sd-tag> and <sd-tag id="sdTag335" source="sdapi" category="entity" entity_type="cell_line" role="experiment" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13402"/></sd-panel><sd-panel panel_id="13403"><p>(B and C) <sd-tag id="sdTag340" source="sdapi" category="assay" entity_type="" role="" text="Confocal microscopy" ext_ids="BAO_0000453" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="confocal microscopy" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">Confocal microscopy</sd-tag> images (B) and analysis of autophagic flux by automated <sd-tag id="sdTag339" source="sdapi" category="assay" entity_type="" role="" text="Cellomics microscope" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Cellomics microscope</sd-tag> (C) show that <sd-tag id="sdTag341" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="L-NAME" ext_ids="CHEBI:7549" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="N(gamma)-nitro-L-arginine methyl ester" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">L-NAME</sd-tag> increased <sd-tag id="sdTag342" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="autolysosomes" ext_ids="GO:0044754" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="autolysosome" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">autolysosomes</sd-tag> in <sd-tag id="sdTag343" source="sdapi" category="entity" entity_type="protein" role="reporter" text="mRFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">mRFP</sd-tag>-<sd-tag id="sdTag344" source="sdapi" category="entity" entity_type="protein" role="reporter" text="GFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">GFP</sd-tag>-<sd-tag id="sdTag345" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q9H492///Q9BXW4///Q9GZQ8" norm_text="" ext_dbs="Uniprot///Uniprot///Uniprot" in_caption="True" ext_names="MAP1LC3A///MAP1LC3C///MAP1LC3B" ext_tax_ids="9606///9606///9606" ext_tax_names="Homo sapiens///Homo sapiens///Homo sapiens" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> <sd-tag id="sdTag346" source="sdapi" category="entity" entity_type="cell_line" role="component" text="HeLa" ext_ids="CVCL_0030" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="HeLa" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://identifiers.org/cellosaurus:">HeLa</sd-tag> cells.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13403"/></sd-panel><sd-panel panel_id="13404"><p>(D) <sd-tag id="sdTag351" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="L-NAME" ext_ids="CHEBI:7549" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="N(gamma)-nitro-L-arginine methyl ester" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">L-NAME</sd-tag> reduced <sd-tag id="sdTag352" source="sdapi" category="entity" entity_type="protein" role="reporter" text="EGFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">EGFP</sd-tag>-<sd-tag id="sdTag349" source="sdapi" category="entity" entity_type="gene" role="component" text="HD" ext_ids="15194" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Htt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">HD</sd-tag>Q74 aggregates in <sd-tag id="sdTag353" source="sdapi" category="entity" entity_type="protein" role="reporter" text="EGFP" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">EGFP</sd-tag>-<sd-tag id="sdTag350" source="sdapi" category="entity" entity_type="protein" role="assayed" text="HD" ext_ids="P42859" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Htt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">HD</sd-tag>Q74-transfected <sd-tag id="sdTag354" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Atg5" ext_ids="11793" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Atg5" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Atg5</sd-tag><sup>+/+</sup>, but not in <sd-tag id="sdTag355" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Atg5" ext_ids="11793" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Atg5" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Atg5</sd-tag><sup>−/−</sup>, <sd-tag id="sdTag356" source="sdapi" category="entity" entity_type="cell_line" role="component" text="MEFs" ext_ids="CL:2000042" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="embryonic fibroblast" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://identifiers.org/cellosaurus:">MEFs</sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13404"/></sd-panel><sd-panel panel_id="13405"><p>(E) <sd-tag id="sdTag358" source="sdapi" category="entity" entity_type="organism" role="component" text="Drosophila" ext_ids="7215" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Drosophila" ext_tax_ids="7215" ext_tax_names="Drosophila" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">Drosophila</sd-tag> expressing mutant <sd-tag id="sdTag359" source="sdapi" category="entity" entity_type="gene" role="component" text="huntingtin" ext_ids="43392" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="htt" ext_tax_ids="7227" ext_tax_names="Drosophila melanogaster" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">huntingtin</sd-tag> exon 1 (Q120) shows a significant decrease in neurodegeneration (p &lt; 0.001, paired t test) upon <sd-tag id="sdTag364" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="L-NAME" ext_ids="CHEBI:7549" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="N(gamma)-nitro-L-arginine methyl ester" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">L-NAME</sd-tag> treatment compared to <sd-tag id="sdTag360" source="sdapi" category="entity" entity_type="molecule" role="component" text="DMSO" ext_ids="CHEBI:28262" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="dimethyl sulfoxide" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DMSO</sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13405"/></sd-panel><sd-panel panel_id="13406"><p>(F) Expression of an endogenous negative regulator of NOS activity (<sd-tag id="sdTag365" source="sdapi" category="entity" entity_type="gene" role="intervention" text="NOS4" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">NOS4</sd-tag>) significantly attenuates neurodegeneration (p &lt; 0.05, paired t test) in <sd-tag id="sdTag366" source="sdapi" category="entity" entity_type="organism" role="component" text="Drosophila" ext_ids="7215" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Drosophila" ext_tax_ids="7215" ext_tax_names="Drosophila" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">Drosophila</sd-tag> expressing mutant <sd-tag id="sdTag367" source="sdapi" category="entity" entity_type="gene" role="intervention" text="huntingtin" ext_ids="43392" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="htt" ext_tax_ids="7227" ext_tax_names="Drosophila melanogaster" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">huntingtin</sd-tag> exon 1 (Q120).</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13406"/></sd-panel><sd-panel panel_id="13407"><p>(G-I) Images from the <sd-tag id="sdTag377" source="sdapi" category="entity" entity_type="tissue" role="component" text="retina" ext_ids="UBERON:0000966" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="retina" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">retina</sd-tag> of transgenic <sd-tag id="sdTag372" source="sdapi" category="entity" entity_type="protein" role="assayed" text="HD" ext_ids="O42269" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="htt" ext_tax_ids="7955" ext_tax_names="Danio rerio" ext_urls="https://www.uniprot.org/uniprot/">HD</sd-tag> <sd-tag id="sdTag370" source="sdapi" category="entity" entity_type="organism" role="component" text="zebrafish" ext_ids="7955" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="zebrafish" ext_tax_ids="7955" ext_tax_names="Danio rerio" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">zebrafish</sd-tag> show mutant <sd-tag id="sdTag373" source="sdapi" category="entity" entity_type="gene" role="component" text="huntingtin" ext_ids="30214" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="htt" ext_tax_ids="7955" ext_tax_names="Danio rerio" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">huntingtin</sd-tag> aggregates (arrows) (G). Treatment with <sd-tag id="sdTag374" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="rapamycin" ext_ids="CHEBI:9168" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="sirolimus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">rapamycin</sd-tag> or <sd-tag id="sdTag375" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="L-NAME" ext_ids="CHEBI:7549" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="N(gamma)-nitro-L-arginine methyl ester" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">L-NAME</sd-tag> reduced the number of aggregates (H). <sd-tag id="sdTag376" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="L-NAME" ext_ids="CHEBI:7549" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="N(gamma)-nitro-L-arginine methyl ester" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">L-NAME</sd-tag> did not reduce aggregates in the presence of <sd-tag id="sdTag371" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="NH4Cl" ext_ids="CHEBI:31206" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="ammonium chloride" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">NH<sub>4</sub>Cl</sd-tag>, which increased aggregate count (I).</p><graphic href="https://api.sourcedata.io/file.php?panel_id=13407"/></sd-panel></fig></article>