{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wu X"],"funding":["Chinese Academy of Sciences","National Key Clinical Specialty Discipline Construction Program of China","National Natural Science Foundation of China","Youth Innovation Promotion Association of the Chinese Academy of Sciences"],"pagination":["46-59"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6174864"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20"],"pubmed_abstract":["Endothelial dysfunction induced by hyperhomocysteinemia (HHcy) plays a critical role in vascular pathology. However, little is known about the role of endoplasmic reticulum (ER) redox homeostasis in HHcy-induced endothelial dysfunction. Here, we show that Hcy induces ER oxidoreductin-1α (Ero1α) expression with ER stress and inflammation in human umbilical vein endothelial cells and in the arteries of HHcy mice. Hcy upregulates Ero1α expression by promoting binding of hypoxia-inducible factor 1α to the ERO1A promoter. Notably, Hcy rather than other thiol agents markedly increases the GSH/GSSG ratio in the ER, therefore allosterically activating Ero1α to produce H<sub>2</sub>O<sub>2</sub> and trigger ER oxidative stress. By contrast, the antioxidant pathway mediated by ER glutathione peroxid"],"journal":["Redox biology"],"pubmed_title":["Homocysteine causes vascular endothelial dysfunction by disrupting endoplasmic reticulum redox homeostasis."],"pmcid":["PMC6174864"],"funding_grant_id":["31571163","81770445","2016YFA0500200","2017YFA0504000","31771261","91439206"],"pubmed_authors":["Yang J","Feng J","Miao Y","Zhang L","Wang X","Wang CC","Wu X","Wang L"],"additional_accession":[]},"is_claimable":false,"name":"Homocysteine causes vascular endothelial dysfunction by disrupting endoplasmic reticulum redox homeostasis.","description":"Endothelial dysfunction induced by hyperhomocysteinemia (HHcy) plays a critical role in vascular pathology. However, little is known about the role of endoplasmic reticulum (ER) redox homeostasis in HHcy-induced endothelial dysfunction. Here, we show that Hcy induces ER oxidoreductin-1α (Ero1α) expression with ER stress and inflammation in human umbilical vein endothelial cells and in the arteries of HHcy mice. Hcy upregulates Ero1α expression by promoting binding of hypoxia-inducible factor 1α to the ERO1A promoter. Notably, Hcy rather than other thiol agents markedly increases the GSH/GSSG ratio in the ER, therefore allosterically activating Ero1α to produce H<sub>2</sub>O<sub>2</sub> and trigger ER oxidative stress. By contrast, the antioxidant pathway mediated by ER glutathione peroxid","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jan","modification":"2026-06-13T04:08:41.247Z","creation":"2019-03-26T23:59:45Z"},"accession":"S-EPMC6174864","cross_references":{"pubmed":["30292945"],"doi":["10.1016/j.redox.2018.09.021"]}}