{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:36:36Z","timestamp":1790742996504,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T00:00:00Z","timestamp":1510617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR\u2010067667"],"award-info":[{"award-number":["AR\u2010067667"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL\u2010107640\u2010NT"],"award-info":[{"award-number":["HL\u2010107640\u2010NT"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>Homocysteine (Hcy) causes endothelial dysfunction by inducing oxidative stress in most neurodegenerative disorders. This dysfunction is highly correlated with mitochondrial dynamics such as fusion and fission. However, there are no strategies to prevent Hcy\u2010induced mitochondrial remodeling. Tetrahydrocurcumin (THC) is an anti\u2010inflammatory and anti\u2010oxidant compound. We hypothesized that THC may ameliorates Hcy\u2010induced mitochondria remodeling in mouse brain endothelial cells (bEnd3) cells. bEnd3 cells were exposed to Hcy treatment in the presence or absence of THC. Cell viability and autophagic cell death were measured with MTT and MDC staining assay. Reactive oxygen species (ROS) production was determined using DCFH\u2010DA staining by confocal microscopy. Autophagy flux was assessed using a conventional GFP\u2010microtubule\u2010associated protein 1 light chain 3 (LC3) dot assay. Interaction of phagophore marker LC\u20103 with mitochondrial receptor NIX was observed by confocal imaging. Mitochondrial fusion and fission were evaluated by western blot and RT\u2010PCR. Our results demonstrated that Hcy resulted in cell toxicity in a dose\u2010dependent manner and supplementation of THC prevented the detrimental effects of Hcy on cell survival. Furthermore, Hcy also upregulated fission marker (DRP\u20101), fusion marker (Mfn2), and autophagy marker (LC\u20103). Finally, we observed that Hcy activated mitochondrial specific phagophore marker (LC\u20103) and co\u2010localized with the mitochondrial receptor NIX, as viewed by confocal microscopy. Pretreatment of bEnd3 with THC (15\u2009\u03bcM) ameliorated Hcy\u2010induced oxidative damage, mitochondrial fission\/fusion, and mitophagy. Our studies strongly suggest that THC has beneficial effects on mitochondrial remodeling and could be developed as a potential therapeutic agent against hyperhomocysteinemia (HHcy) induced mitochondrial dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.26145","type":"journal-article","created":{"date-parts":[[2017,8,19]],"date-time":"2017-08-19T03:36:37Z","timestamp":1503113797000},"page":"3080-3092","source":"Crossref","is-referenced-by-count":35,"title":["Tetrahydrocurcumin ameliorates homocysteine\u2010mediated mitochondrial remodeling in brain endothelial cells"],"prefix":"10.1002","volume":"233","author":[{"given":"Jonathan C.","family":"Vacek","sequence":"first","affiliation":[{"name":"Department of Physiology School of Medicine, Health Sciences Center University of Louisville Louisville Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyotirmaya","family":"Behera","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine, Health Sciences Center University of Louisville Louisville Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash K.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine, Health Sciences Center University of Louisville Louisville Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradip K.","family":"Kamat","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine, Health Sciences Center University of Louisville Louisville Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Kalani","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine, Health Sciences Center University of Louisville Louisville Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0285-5072","authenticated-orcid":false,"given":"Neetu","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine, Health Sciences Center University of Louisville Louisville Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.08.008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3988\/jcn.2014.10.4.281"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.81"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2694"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2008.12.012"},{"key":"e_1_2_9_7_1","first-page":"3527","article-title":"Endothelial cells in physiology and in the pathophysiology of vascular disorders","volume":"91","author":"Cines D. 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