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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, MJ; Moon, CH; Kim, MY; Lee, S; Yi, KY; Yoo, SE; Lee, SH; Baik, EJ; Jung, YS
Citation
European journal of pharmacology, 525(1-3):1-7, 2005
Journal Title
European journal of pharmacology
ISSN
0014-29991879-0712
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.
MeSH terms
AnimalsAnoxia*Calcium/metabolismCardiotonic Agents/pharmacology*Caspase 3Caspases/metabolismCell Death/drug effects*Cell LineGuanidines/pharmacology*L-Lactate Dehydrogenase/metabolismMembrane Potentials/drug effectsMitochondria/drug effectsMitochondria/metabolismMitochondria/physiologyMyocytes, Cardiac/drug effects*Myocytes, Cardiac/metabolismMyocytes, Cardiac/physiologyRatsSodium-Hydrogen Antiporter/antagonists & inhibitors
DOI
10.1016/j.ejphar.2005.09.043
PMID
16289528
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
문, 창현이, 수환백, 은주정, 이숙
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