title: Probucol Protects Against Asymmetric Dimethylarginine-Induced Apoptosis in the Cultured Human Brain Microvascular Endothelial Cells.
abstract: Asymmetric dimethylarginine (ADMA) is emerging as a key contributor to endothelial dysfunction. The drug probucol was reported to have an anti-lipid peroxidation effect and improve endothelial dilation function. But little is known about the protective effect of probucol on ADMA-induced human brain microvascular endothelial cell (HBMEC) injury and its underlying mechanisms. Therefore, in this study, we investigated the effect of probucol on ADMA-induced HBMEC injury and its potential mechanisms. Results showed that probucol protected against ADMA-induced HBMEC injury in a dose-dependent manner; probucol pretreatment also significantly reduced the level of reactive oxygen species (ROS) and malondialdehyde (MDA), downregulated the expression of pro-apoptotic gene Bax and caspase-3 activity, as well as increased the brain-derived neurotrophic factor (BDNF) release and promoted anti-apoptotic gene Bcl-2 and eNOS expression in the cultured HBMECs. Furthermore, we found that ADMA significantly increased the phosphorylation of c-Jun NH2-terminal kinase (JNK) and p38, while probucol pretreatment effectively inhibited ADMA-induced JNK and p38 phosphorylation in HBMECs. In conclusion, our present results demonstrated that probucol protected against ADMA-induced HBMEC injury and suppressed oxidative stress through the JNK/p38 MAPK pathway, which was the potential underlying mechanism of HBMEC injury in ischemic cerebrovascular disease.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, No.88 Jiangkang Road, Xinxiang, Weihui, 453100, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, No.88 Jiangkang Road, Xinxiang, Weihui, 453100, China.
authors.forename: Shupeng
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, No.88 Jiangkang Road, Xinxiang, Weihui, 453100, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, No.88 Jiangkang Road, Xinxiang, Weihui, 453100, China.
authors.forename: Haigang
authors.initials: H
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, No.88 Jiangkang Road, Xinxiang, Weihui, 453100, China.
authors.forename: Pengju
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, No.88 Jiangkang Road, Xinxiang, Weihui, 453100, China. baozhe_jin@163.com.
authors.forename: Baozhe
authors.initials: B
authors.lastname: Jin
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D001120:Arginine / Q000031:analogs & derivatives / Q000633:toxicity; D001921:Brain / Q000098:blood supply; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D055806:Microvessels / Q000166:cytology; D018384:Oxidative Stress; D011341:Probucol / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; C487735:dimethylarginine; D001120:Arginine; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D011341:Probucol
keywords: Asymmetric dimethylarginine; Cell injury; Human brain microvascular endothelial cells; Probucol; Reactive oxygen species