title: Mitochondria dependent pathway is involved in the protective effect of bestrophin-3 on hydrogen peroxide-induced apoptosis in basilar artery smooth muscle cells.
abstract: Bestrophin 3 (Best-3) is expressed in a variety of tissues, such as cardiac, smooth muscle and renal tissues, and it is highly expressed in rat basilar arterial smooth muscle cells (BASMCs). Lee et al. (Biochim Biophys Acta 1823:1864-1876, 2012) reported that Best-3 prevented apoptotic cell death induced by endoplasmic reticulum stress. In the present study, we used small interference RNA (siRNA) and bestrophin 3 cDNA transfection strategy to investigate whether Best-3 can provide a protective effect on apoptosis induced by hydrogen peroxide (H2O2) in BASMCs and studied the underlying mechanisms. We found that silencing of Best-3 with siRNA resulted in an increased H2O2-induced apoptosis and a decreased cell viability, whereas overexpression of Best-3 significantly prevented the apoptotic cell death and increased the cell viability. Overexpression of Best-3 could stabilize the mitochondrial membrane potential, increase the ratio of Bcl-2/Bax, and decrease cytochrome c release and caspase-3 activation. In contrast, silencing of Best-3 produced the opposite effects. Our present data strongly suggest that Best-3 inhibits apoptosis induced by H2O2 in BASMCs through mitochondria dependent pathway.
authors.affiliation: Department of Pharmacology, Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan 2 Road, Guangzhou 510080, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Ma
authors.forename: Yong-Bo
authors.initials: YB
authors.lastname: Tang
authors.forename: Jia-Guo
authors.initials: JG
authors.lastname: Zhou
authors.forename: Yong-Yuan
authors.initials: YY
authors.lastname: Guan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001488:Basilar Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000075002:Bestrophins; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D015870:Gene Expression; D020868:Gene Silencing; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C568920:Best3 protein, rat; D000075002:Bestrophins; D018118:Chloride Channels; D034741:RNA, Small Interfering; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D053148:Caspase 3