Nicorandil regulates Bcl-2 family proteins and protects cardiac myocytes against hypoxia-induced apoptosis

Journal of Molecular and Cellular Cardiology
Susumu NishikawaHiroaki Matsubara

Abstract

Nicorandil has been shown to inhibit myocyte apoptosis by opening of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels and nitrate-like effect against oxidative stress. However, the detailed mechanism of nicorandil-mediated cardioprotection under hypoxic conditions remains to be largely unknown. The present study examined whether nicorandil can inhibit apoptosis via regulation of Bcl-2 family proteins in hypoxic myocytes. Neonatal rat cardiac myocytes were exposed to hypoxia for 7 hours. Hypoxia-induced myocyte apoptosis (13.9+/-0.9%) under glucose-rich conditions. Myocyte apoptosis was accompanied by loss of mitochondrial membrane potential (Deltapsi(m)), cytochrome c release from mitochondria into cytosol, and activation of caspase-3. Hypoxia also significantly increased Bax and decreased Bcl-2 mRNA and protein expression, thereby increasing Bax/Bcl-2 ratio. Nicorandil 100 micromol/l significantly decreased the percentage of apoptotic myocytes (7.2+/-0.5%) by inhibiting loss of Deltapsi(m) and translocation of cytochrome c. These effects of nicorandil were partially but significantly inhibited by cotreatment of either 500 micromol/l 5-hydroxydecanoate, a selective mitoK(ATP) channel antagonist, or 10 micromol/l 1H-[...Continue Reading

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Citations

Mar 26, 2014·Apoptosis : an International Journal on Programmed Cell Death·Keke ChenFeng Gao
May 13, 2010·Biomedical Research·Takashi MuraguchiShunichiro Kubota
Feb 13, 2010·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yiguo SunXiaoxiang Zheng
Apr 23, 2014·Journal of Cardiac Surgery·Flora Hau Fung TsangYiu-Fai Cheung
Oct 17, 2014·Cardiovascular Therapeutics·Fujie ZhaoDao Wen Wang
Mar 5, 2016·Journal of Cardiovascular Pharmacology and Therapeutics·Muhammad Z AfzalJennifer L Strande
Nov 28, 2006·Circulation Journal : Official Journal of the Japanese Circulation Society·Chuanjiang LuHisayoshi Fujiwara
May 23, 2012·Journal of Cardiovascular Medicine·Ailing WangYuanxun Yu

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