首页 | 本学科首页   官方微博 | 高级检索  
     


KR-32570, a novel Na+/H+ exchanger-1 inhibitor, attenuates hypoxia-induced cell death through inhibition of intracellular Ca2+ overload and mitochondrial death pathway in H9c2 cells
Authors:Kim Mi Jeong  Moon Chang-Hyun  Kim Mi-Young  Lee Sunkyung  Yi Kyu Yang  Yoo Sung Eun  Lee Soo Hwan  Baik Eun Joo  Jung Yi-Sook
Affiliation:Department of Physiology, Ajou University School of Medicine, #5 Woncheon-dong, Suwon 442-749, South Korea.
Abstract:
A novel Na+/H+ exchanger-1 (NHE-1) inhibitor [5-(2-methoxy-5-chloro-5-phenyl)furan-2-ylcarbonyl]guanidine (KR-32570) has been previously demonstrated to elicit cardioprotective effect against ischemic injury in rat heart. In the present study, we examined the effects of KR-32570 on cell death induced by hypoxic insult in heart-derived H9c2 cells. Treatment with KR-32570 (1-10 microM) significantly reduced hypoxia-induced necrotic cell death (lactate dehydrogenase release) and apoptotic cell death (TUNEL-positivity, caspase-3 activity). KR-32570 also decreased the cytosolic and mitochondrial Ca2+ overload induced by hypoxia. Inhibition of mitochondrial Ca2+ overload by ruthenium red mimicked the anti-apoptotic effect of KR-32570. In addition, KR-32570 significantly recovered the large reduction in mitochondrial membrane potential (delta psi(m)) and cytochrome c release induced by hypoxia. Taken together, our results suggest that a new NHE-1 inhibitor KR-32570 elicits potent cardioprotective effects in H9c2 cells, and its effects may be mediated by inhibition of intracellular Ca2+ overload and mitochondrial death pathway during hypoxia.
Keywords:
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号