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.
Eur J Pharmacol
; 525(1-3): 1-7, 2005 Nov 21.
Article
em En
| MEDLINE
| ID: mdl-16289528
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cardiotônicos
/
Morte Celular
/
Miócitos Cardíacos
/
Guanidinas
/
Hipóxia
Limite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Coréia do Sul