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
- Dong Hee Lee Chung Soo Lee
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제10권 제1호
- 등재여부 : KCI등재
- 2006.01
- 51 - 57 (7 pages)
The promoting effect of hydrogen peroxide (H<SUB>2</SUB>O<SUB>2</SUB>) against the cytotoxicity of 1-methyl-4-phenylpyridinium (MPP<SUP>⁢</SUP>) in differentiated PC12 cells was assessed by measuring the effect on the mitochondrial membrane permeability. Treatment of PC12 cells with MPP<SUP>⁢</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>⁢</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>⁢</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>⁢</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>⁢</SUP> against PC12 cells. H<SUB>2</SUB>O<SUB>2</SUB> may enhance the MPP<SUP>⁢</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.