{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:47:10Z","timestamp":1770742030054,"version":"3.49.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Sulfur dioxide (SO<jats:sub>2<\/jats:sub>) is an important gas signal molecule produced in the cardiovascular system, so it has an important regulatory effect on human umbilical vascular endothelial cells (HUVECs). Studies have shown that high glucose (HG) has become the main cause of endothelial dysfunction and aging. However, the mechanism by which SO<jats:sub>2<\/jats:sub> regulates the senescence of vascular endothelial cells induced by HG has not yet been clarified, so it is necessary to find effective tools to elucidate the effect of SO<jats:sub>2<\/jats:sub> on senescence of HUVECs. In this paper, we identified a novel sulfur dioxide probe (2-(4-(dimethylamino)styryl)-1,1,3-trimethyl-1H-benzo [e]indol-3-ium, DLC) that inhibited the senescence of HUVECs. Our results suggested that DLC facilitated lipid droplets (LDs) translocation to lysosomes and triggered upregulation of LAMP1 protein levels by targeting LDs. Further study elucidated that DLC inhibited HG-induced HUVECs senescence by promoting the decomposition of LDs and protecting the proton channel of V-ATPase on lysosomes. In conclusion, our study revealed the regulatory effect of lipid droplet-targeted sulfur dioxide probes DLC on HG-induced HUVECs senescence. At the same time, it provided the new experimental evidence for elucidating the regulatory mechanism of intracellular gas signaling molecule sulfur dioxide on vascular endothelial fate.<\/jats:p>","DOI":"10.3389\/fphys.2022.979986","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T05:04:15Z","timestamp":1671167055000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["A novel sulfur dioxide probe inhibits high glucose-induced endothelial cell senescence"],"prefix":"10.3389","volume":"13","author":[{"given":"Hui","family":"Ren","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"WenWen","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"BaoXiang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JunYing","family":"Miao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ZhaoMin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1053\/j.seminoncol.2017.10.013","article-title":"LAMPs: Shedding light on cancer biology","volume":"44","author":"Alessandrini","year":"2017","journal-title":"Semin. Oncol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"277","DOI":"10.33594\/000000373","article-title":"Lysosome function in cardiovascular diseases","volume":"55","author":"Bhat","year":"2021","journal-title":"Cell. Physiol. biochem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1159\/000358676","article-title":"Autophagy protects against senescence and apoptosis via the RAS-mitochondria in high-glucose-induced endothelial cells","volume":"33","author":"Chen","year":"2014","journal-title":"Cell. Physiol. biochem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1111\/j.1745-7254.2008.00845.x","article-title":"Endogenously generated sulfur dioxide and its vasorelaxant effect in rats","volume":"29","author":"Du","year":"2008","journal-title":"Acta Pharmacol. Sin."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1161\/CIRCRESAHA.116.302855","article-title":"Endothelial cell metabolism in normal and diseased vasculature","volume":"116","author":"Eelen","year":"2015","journal-title":"Circ. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nrm2272","article-title":"Vacuolar ATPases: Rotary proton pumps in physiology and pathophysiology","volume":"8","author":"Forgac","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"5053","DOI":"10.3390\/molecules25215053","article-title":"Friend or foe: Lipid droplets as organelles for protein and lipid storage in cellular stress response, aging and disease","volume":"25","author":"Geltinger","year":"2020","journal-title":"Molecules"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1016\/j.bbalip.2014.10.004","article-title":"Phospholipase A2 regulation of lipid droplet formation","volume":"1841","author":"Guijas","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"B9","doi-asserted-by":"publisher","first-page":"3383","DOI":"10.1158\/0008-5472.CAN-20-0506","article-title":"Senescent stromal cells promote cancer resistance through SIRT1 loss-potentiated overproduction of small extracellular vesicles","volume":"80","author":"Han","year":"2020","journal-title":"Cancer Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1089\/ars.2021.0213","article-title":"Sulfur dioxide: Endogenous generation, biological effects, detection, and therapeutic potential","volume":"36","author":"Huang","year":"2022","journal-title":"Antioxid. Redox Signal."},{"key":"B11","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/nature11654","article-title":"An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast","volume":"492","author":"Hughes","year":"2012","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1080\/15548627.2015.1124226","article-title":"AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA","volume":"12","author":"Kaushik","year":"2016","journal-title":"Autophagy"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1161\/CIRCRESAHA.116.310498","article-title":"Lipid droplet biogenesis and function in the endothelium","volume":"120","author":"Kuo","year":"2017","journal-title":"Circ. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.yjmcc.2003.11.010","article-title":"Vascular cell senescence and vascular aging","volume":"36","author":"Minamino","year":"2004","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1146\/annurev-physiol-012110-142317","article-title":"Lysosomal acidification mechanisms","volume":"74","author":"Mindell","year":"2012","journal-title":"Annu. Rev. Physiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"140443","DOI":"10.1016\/j.bbapap.2020.140443","article-title":"The aging lysosome: An essential catalyst for late-onset neurodegenerative diseases","volume":"1868","author":"Nixon","year":"2020","journal-title":"Biochim. Biophys. Acta. Proteins Proteom."},{"key":"B17","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41580-018-0085-z","article-title":"Dynamics and functions of lipid droplets","volume":"20","author":"Olzmann","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2776","DOI":"10.1002\/jcp.29182","article-title":"Deacetylation of LAMP1 drives lipophagy-dependent generation of free fatty acids by Abrus agglutinin to promote senescence in prostate cancer","volume":"235","author":"Panda","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.3390\/molecules23081941","article-title":"Lipid droplets in cancer: Guardians of fat in a stressful world","volume":"23","author":"Petan","year":"2018","journal-title":"Molecules"},{"key":"B20","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.bbrc.2021.07.078","article-title":"Identification of a new autophagy inhibitor targeting lipid droplets in vascular endothelial cells","volume":"571","author":"Ren","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1186\/s13287-018-1081-0","article-title":"A pH probe inhibits senescence in mesenchymal stem cells","volume":"9","author":"Wang","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"B22","doi-asserted-by":"publisher","first-page":"31950","DOI":"10.1074\/jbc.M114.600015","article-title":"Orexin\/hypocretin activates mTOR complex 1 (mTORC1) via an Erk\/Akt-independent and calcium-stimulated lysosome v-ATPase pathway","volume":"289","author":"Wang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e130056","DOI":"10.1172\/jci.insight.130056","article-title":"Secretion of leukotrienes by senescent lung fibroblasts promotes pulmonary fibrosis","volume":"4","author":"Wiley","year":"2019","journal-title":"JCI Insight"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1038\/s42255-021-00483-8","article-title":"The metabolic roots of senescence: Mechanisms and opportunities for intervention","volume":"3","author":"Wiley","year":"2021","journal-title":"Nat. Metab."},{"key":"B25","doi-asserted-by":"publisher","first-page":"604","DOI":"10.4161\/cib.3.6.13364","article-title":"On the role of v-ATPase V0a1-dependent degradation in Alzheimer disease","volume":"3","author":"Williamson","year":"2010","journal-title":"Commun. Integr. Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1089\/rej.2006.0535","article-title":"Autophagy in the heart and liver during normal aging and calorie restriction","volume":"10","author":"Wohlgemuth","year":"2007","journal-title":"Rejuvenation Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.aca.2020.09.002","article-title":"A synergetic FRET\/ICT platform-based fluorescence probe for ratiometric imaging of bisulfite in lipid droplets","volume":"1137","author":"Yan","year":"2020","journal-title":"Anal. Chim. Acta"},{"key":"B28","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13045-021-01087-1","article-title":"Role of lysosomes in physiological activities, diseases, and therapy","volume":"14","author":"Zhang","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1080\/15548627.2019.1598750","article-title":"Long noncoding RNA CA7-4 promotes autophagy and apoptosis via sponging MIR877-3P and MIR5680 in high glucose-induced vascular endothelial cells","volume":"16","author":"Zhao","year":"2020","journal-title":"Autophagy"}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.979986\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T05:04:16Z","timestamp":1671167056000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.979986\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,16]]},"references-count":29,"alternative-id":["10.3389\/fphys.2022.979986"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.979986","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,16]]},"article-number":"979986"}}