{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:50:52Z","timestamp":1778770252600,"version":"3.51.4"},"reference-count":55,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ethanol (ET) causes cerebrovascular dysfunction by altering homocysteine (Hcy) metabolism and by causing oxidative stress. However, there are no strategies to prevent ET\u2010induced epigenetic deregulation of tight junction protein (hyper\u2010methylation) and endothelial cell permeability to date. Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) has an antioxidative, antiapoptotic, and anti\u2010inflammatory effect. Here, we investigated the protective role of H<jats:sub>2<\/jats:sub>S in ET\u2010induced endothelial permeability through epigenetic changes in mouse brain endothelial cells (bEnd3). The bEnd3 cells were exposed to 50\u2009mM ET treatment in the presence or absence of 50\u2009\u03bcM NaHS (H<jats:sub>2<\/jats:sub>S donor). The result demonstrates that ET\u2010induced cellular toxicity increased intracellular Hcy levels, which further intensified mitochondrial dysfunction and energy defects. Using miScript microRNA (miRNA) polymerase chain reaction\u00a0array\u2010based screening, we identified a particular miRNA, miR\u2010218, as a novel target of ET\u2010induced DNA methyltransferase\u20103a (DNMT3a) activation. miR\u2010218 influences CpG island methylation of the zonula occludens 1 (ZO\u20101) promoter in the endothelial cells. We discovered that ET suppressed miR\u2010218 levels and induced endothelial permeability via DNMT3a\u2010mediated ZO\u20101 hyper\u2010methylation. Treatment with mito\u2010TEMPO (mitochondria\u2010targeted antioxidant), 5\u2032\u2010azacitidine (DNMT inhibitor), or miR\u2010218 overexpression was shown to protect endothelial cells against ET\u2010induced permeability. Also, bEnd3 cells pretreated with NaHS attenuated ET\u2010induced vascular permeability and prevented CpG island methylation at the promoter. In conclusion, our data provide evidence that H<jats:sub>2<\/jats:sub>S treatment protects vascular integrity from ET\u2010induced stress by mitigating CpG (ZO\u20101 promoter) DNA hyper\u2010methylation. This finding uncovers a new mechanistic understanding of NaHS\/H<jats:sub>2<\/jats:sub>S, that may have therapeutic potential in preventing or diminishing ET\u2010induced brain vascular permeability and dysfunction induced by alcoholism.<\/jats:p>","DOI":"10.1002\/jcp.30382","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T21:47:46Z","timestamp":1618523266000},"page":"6852-6867","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Hydrogen sulfide prevents ethanol\u2010induced ZO\u20101 CpG promoter hypermethylation\u2010dependent vascular permeability via miR\u2010218\/DNMT3a axis"],"prefix":"10.1002","volume":"236","author":[{"given":"Jyotirmaya","family":"Behera","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine University of Louisville  Louisville Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly 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