{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T12:18:10Z","timestamp":1793017090380,"version":"4.5.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770422 82070445 81921001 81900872"],"award-info":[{"award-number":["81770422 82070445 81921001 81900872"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7191012"],"award-info":[{"award-number":["7191012"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Objectives:<\/jats:bold> The study was designed to explore the role of endogenous gaseous signaling molecule sulfur dioxide (SO<jats:sub>2<\/jats:sub>) in the control of cardiomyocyte apoptosis and its molecular mechanisms.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Neonatal mouse cardiac myocytes (NMCMs) and H9c2 cells were used in the cell experiments. The endogenous SO<jats:sub>2<\/jats:sub> pathway including SO<jats:sub>2<\/jats:sub> level and the expression of SO<jats:sub>2<\/jats:sub>-generating enzyme aspartate aminotransferase 1\/2 (AAT1\/2) were detected in NMCMs. The apoptosis of cardiomyocytes was examined by a TUNEL assay. The cleavage and the activity of apoptotic proteins caspase9 and caspase3 were measured. The content of ATP, the opening of mitochondrial permeability transition pore (mPTP), and the cytochrome c (cytc) leakage were detected by immunofluorescence. The sulphenylation of cyclophilin-D (CypD) was detected by biotin switch analysis. The four CypD mutant plasmids in which cysteine sites were mutated to serine were constructed to identify the SO<jats:sub>2<\/jats:sub>-affected site <jats:italic>in vitro<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> ISO down-regulated the endogenous SO<jats:sub>2<\/jats:sub>\/AAT pathway of cardiomyocytes in association with a significant increase in cardiomyocyte apoptosis, demonstrated by the increases in apoptosis, cleaved-caspase3\/caspase3 ratio, and caspase3 activity. Furthermore, ISO significantly reduced ATP production in H9c2 cells, but the supplement of SO<jats:sub>2<\/jats:sub> significantly restored the content of ATP. ISO stimulated mPTP opening, resulting in an increase in the release of cytc, which further increased the ratio of cleaved caspase9\/caspase9 and enhanced the protein activity of caspase9. While, the supplementation of SO<jats:sub>2<\/jats:sub> reversed the above effects. Mechanistically, SO<jats:sub>2<\/jats:sub> did not affect CypD protein expression, but sulphenylated CypD and inhibited mPTP opening, resulting in an inhibition of cardiomyocyte apoptosis. The C104S mutation in CypD abolished SO<jats:sub>2<\/jats:sub>-induced sulphenylation of CypD, and thereby blocked the inhibitory effect of SO<jats:sub>2<\/jats:sub> on the mPTP opening and cardiomyocyte apoptosis.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Endogenous SO<jats:sub>2<\/jats:sub> sulphenylated CypD at Cys104 to inhibit mPTP opening, and thus protected against cardiomyocyte apoptosis.<\/jats:p>","DOI":"10.3389\/fcell.2021.784799","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T05:45:32Z","timestamp":1642484732000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Sulphenylation of CypD at Cysteine 104: A Novel Mechanism by Which SO2 Inhibits Cardiomyocyte Apoptosis"],"prefix":"10.3389","volume":"9","author":[{"given":"Boyang","family":"Lv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingquan","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingfang","family":"Bu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiantong","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoshu","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbao","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfang","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.hfc.2011.08.010","article-title":"Role of Apoptosis in Adverse Ventricular Remodeling","volume":"8","author":"Abbate","year":"2012","journal-title":"Heart Fail. 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