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Summary. The present study investigated the effect of 5-hydroxydecanoate, a selective mitochondrial KATP channel blocker, on the cytotoxicity of neurotoxin 1-methyl-4-phenylpyridinium (MPP ) in differentiated PC12 cells. 5-Hydroxydecanoate and glibenclamide (a cell surface and mitochondrial KATP channel inhibitor) reduced the MPP -induced cell death and GSH depletion and showed a maximal inhibitory effect at 5 and 10 [mu]M, respectively. Addition of 5-hydroxydecanoate attenuated the MPP -induced nuclear damage, changes in the mitochondrial membrane permeability and increase in the reactive oxygen species formation in PC12 cells. The results show that 5-hydroxydecanote may prevent the MPP -induced viability loss in PC12 cells by suppressing formation of the mitochondrial permeability transition, leading to the cytochrome c release and caspase-3 activation. This effect appears to be accomplished by the inhibitory action on the formation of reactive oxygen species and the depletion of GSH. The blockade of mitochondrial KATP channels seems to prevent the MPP -induced neuronal cell damage.

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