Promoting Effect of Hydrogen Peroxide on 1-Methyl-4-phenylpyridinium-induced Mitochondrial Dysfunction and Cell Death in PC12 Cells.
- Author:
Dong Hee LEE
1
;
Chung Soo LEE
Author Information
1. Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Korea. leecs@cau.ac.kr
- Publication Type:Original Article
- Keywords:
1-Methyl-4-phenylpyridinium;
H2O2;
PC12 cells;
Mitochondrial membrane permeability;
Cell injury
- MeSH:
1-Methyl-4-phenylpyridinium;
Acetylcysteine;
Animals;
Caspase 3;
Catalase;
Cell Death*;
Cyclosporine;
Cytochromes c;
Cytosol;
Hydrogen Peroxide*;
Hydrogen*;
Membrane Potentials;
Mitochondrial Membranes;
Neurons;
Neurotoxins;
PC12 Cells*;
Permeability;
Reactive Oxygen Species;
Trifluoperazine
- From:The Korean Journal of Physiology and Pharmacology
2006;10(1):51-58
- CountryRepublic of Korea
- Language:English
-
Abstract:
The promoting effect of hydrogen peroxide (H2O2) against the cytotoxicity of 1-methyl-4-phenylpyridinium (MPP+) in differentiated PC12 cells was assessed by measuring the effect on the mitochondrial membrane permeability. Treatment of PC12 cells with MPP+ 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 H2O2 enhanced the MPP+-induced nuclear damage and cell death. Catalase, Carboxy-PTIO, Mn-TBAP, N-acetylcysteine, cyclosporin A and trifluoperazine inhibited the cytotoxic effect of MPP+ in the presence of H2O2. Addition of H2O2 promoted the change in the mitochondrial membrane permeability, ROS formation and decrease in GSH contents due to MPP+ in PC12 cells. The results show that the H2O2 treatment promotes the cytotoxicity of MPP+ against PC12 cells. H2O2 may enhance the MPP+-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 H2O2 as a promoting agent for the formation of mitochondrial permeability transition may enhance the neuronal cell injury caused by neurotoxins.
