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.

Cite this paper

@article{Jung2003KR31466AB, title={KR-31466, a benzopyranylindol analog, attenuates hypoxic injury through mitochondrial K(ATP) channel and protein kinase C activation in heart-derived H9c2 cells.}, author={Yi-sook Jung and Yoon Seok Jung and Mi-Young Kim and Min Hwa Kim and Sunkyung Lee and Kyu Yang Yi and Sung Eun Yoo and Soo Hwan Lee and Eun Baik and Chang-Hyun Moon and Joon Pil Cho}, journal={Journal of pharmacological sciences}, year={2003}, volume={92 1}, pages={13-8} }