Korean J Physiol Pharmacol.  2006 Feb;10(1):51-58.

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

• Lee DH
• Lee CS

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.

Keyword

1-Methyl-4-phenylpyridinium; H2O2; PC12 cells; Mitochondrial membrane permeability; Cell injury

MeSH Terms

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
1-Methyl-4-phenylpyridinium
Acetylcysteine
Caspase 3
Catalase
Cyclosporine
Cytochromes c
Hydrogen
Hydrogen Peroxide
Neurotoxins
Reactive Oxygen Species
Trifluoperazine