Promoting Effect of Hydrogen Peroxide on 1-Methyl-4-phenylpyridinium-induced Mitochondrial Dysfunction and Cell Death in PC12 Cells

Promoting Effect of Hydrogen Peroxide on 1-Methyl-4-phenylpyridinium-induced Mitochondrial Dysfunction and Cell Death in PC12 Cells

The promoting effect of hydrogen peroxide (H<SUB>2</SUB>O<SUB>2</SUB>) against the cytotoxicity of 1-methyl-4-phenylpyridinium (MPP<SUP>&#8290;</SUP>) in differentiated PC12 cells was assessed by measuring the effect on the mitochondrial membrane permeability. Treatment of PC12 cells with MPP<SUP>&#8290;</SUP> resulted in the nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species (ROS) and depletion of GSH. Addition of H<SUB>2</SUB>O<SUB>2</SUB> enhanced the MPP<SUP>&#8290;</SUP>-induced nuclear damage and cell death. Catalase, Carboxy- PTIO, Mn-TBAP, N-acetylcysteine, cyclosporin A and trifluoperazine inhibited the cytotoxic effect of MPP<SUP>&#8290;</SUP><SUB> </SUB>in the presence of H<SUB>2</SUB>O<SUB>2</SUB>. Addition of H<SUB>2</SUB>O<SUB>2</SUB> promoted the change in the mitochondrial membrane permeability, ROS formation and decrease in GSH contents due to MPP<SUP>&#8290;</SUP><SUB> </SUB>in PC12 cells. The results show that the H<SUB>2</SUB>O<SUB>2</SUB> treatment promotes the cytotoxicity of MPP<SUP>&#8290;</SUP> against PC12 cells. H<SUB>2</SUB>O<SUB>2</SUB> may enhance the MPP<SUP>&#8290;</SUP>-induced viability loss in PC12 cells by promoting the mitochondrial membrane permeability change, release of cytochrome c and subsequent activation of caspase-3, which is associated with the increased formation of ROS and depletion of GSH. The findings suggest that H<SUB>2</SUB>O<SUB>2</SUB> as a promoting agent for the formation of mitochondrial permeability transition may enhance the neuronal cell injury caused by neurotoxins.