Inhibition of SIN-1-induced change in mitochondrial membrane permeability in PC12 cells by dopamine

초록

Dopamine (50 or 100 muM) attenuated the nuclear damage and cell death due to 500 muM SIN-1, a donor of superoxide and nitric oxide, in differentiated PC12 cells whereas 200 muM dopamine did not depress cell death. Dopamine at 50-100 muM for a 4-h treatment did not show a significant cytotoxic effect on PC12 cells. Dopamine (100 muM) inhibited the decrease in mitochondrial transmembrane potential, cytochrome c release, activation of caspase-3, formation of reactive oxygen species, and depletion of glutathione (GSH) due to 500 muM SIN-1 in PC12 cells. The reaction of dopamine with peroxynitrite reduced an amount of peroxynitrite. The results suggest that dopamine exhibits a biphasic effect against the cytotoxicity of SIN-1 depending on concentrations. Dopamine at 50-100 muM may attenuate the reactive nitrogen species-induced viability loss in PC12 cells by suppressing the mitochondrial membrane permeability change through inhibition of the formation of reactive species, including peroxynitrite.

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