KR-31466, a benzopyranylindol analog, attenuates hypoxic injury through mitochondrial K(ATP) channel and protein kinase C activation in heart-derived H9c2 cells.

Abstract:

:In the present study, we investigated whether a novel benzopyranylindol analogue, KR-31466 (KR466) (1-[(2S,3R,4S)-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-6-nitro-2H-1-benzopyran-4-yl]-1H-indole-2-carboxylic acid ethyl ester) can attenuate hypoxic injury in heart-derived H9c2 cells and, if so, whether the protective effect of KR466 is mediated through mitochondrial ATP-sensitive potassium (mtK(ATP)) opening. The treatment of H9c2 cells with KR466 (3 - 30 microM) significantly reduced hypoxia-induced cell death in a concentration-dependent manner, as shown by lactate dehydrogenase release and propidium iodide-uptake. In addition, KR466 (10 microM) significantly reduced the increase in hypoxia-induced TUNEL-positive cells, suggesting its anti-apoptotic potential in H9c2 cells. The protective effects of KR466 were abolished by 5-hydroxydecanoate, a specific blocker of the mtK(ATP) channel, suggesting the involvement of the mtK(ATP) channel in the protective effect of KR466. A specific inhibitor of protein kinase C (PKC), chelerythrine (3 microM), significantly attenuated the protective effect of KR466 against hypoxia-induced cardiac cell death. In conclusion, our results suggest that KR466 can protect H9c2 cells from hypoxia-induced death through mtK(ATP) channel opening and PKC activation.

journal_name

J Pharmacol Sci

authors

Jung YS,Jung YS,Kim MY,Kim MH,Lee S,Yi KY,Yoo SE,Lee SH,Baik EJ,Moon CH,Cho JP

doi

10.1254/jphs.92.13

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

13-8

issue

1

eissn

1347-8613

issn

1347-8648

journal_volume

92

pub_type

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