Mitochondria dependent pathway is involved in the protective effect of bestrophin-3 on hydrogen peroxide-induced apoptosis in basilar artery smooth muscle cells

Lei Jiang; Yun Liu; Ming-Ming Ma; Yong-Bo Tang; Jia-Guo Zhou; Yong-Yuan Guan

doi:10.1007/s10495-013-0828-4

Mitochondria dependent pathway is involved in the protective effect of bestrophin-3 on hydrogen peroxide-induced apoptosis in basilar artery smooth muscle cells

Apoptosis. 2013 May;18(5):556-65. doi: 10.1007/s10495-013-0828-4.

Authors

Lei Jiang¹, Yun Liu, Ming-Ming Ma, Yong-Bo Tang, Jia-Guo Zhou, Yong-Yuan Guan

Affiliation

¹ 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.

PMID: 23468120
DOI: 10.1007/s10495-013-0828-4

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Basilar Artery / cytology
Basilar Artery / drug effects
Basilar Artery / metabolism*
Bestrophins
Caspase 3 / genetics
Caspase 3 / metabolism
Cell Survival / drug effects
Chloride Channels / antagonists & inhibitors
Chloride Channels / genetics*
Chloride Channels / metabolism
Cytochromes c / metabolism
Gene Expression
Gene Silencing
Hydrogen Peroxide / pharmacology
Male
Membrane Potential, Mitochondrial / drug effects
Mitochondria / drug effects
Mitochondria / genetics
Mitochondria / metabolism*
Myocytes, Smooth Muscle / cytology
Myocytes, Smooth Muscle / drug effects
Myocytes, Smooth Muscle / metabolism*
Primary Cell Culture
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction
bcl-2 Homologous Antagonist-Killer Protein / genetics
bcl-2 Homologous Antagonist-Killer Protein / metabolism
bcl-2-Associated X Protein / genetics
bcl-2-Associated X Protein / metabolism

Substances

Best3 protein, rat
Bestrophins
Chloride Channels
RNA, Small Interfering
bcl-2 Homologous Antagonist-Killer Protein
bcl-2-Associated X Protein
Cytochromes c
Hydrogen Peroxide
Caspase 3