Monoamine Oxidase Inhibitors Attenuate Cytotoxicity of 1-Methyl-4-phenylpyridinium by Suppressing Mitochondrial Permeability Transition.
- Author:
Chung Soo LEE
1
Author Information
1. Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Korea. leecs@cau.ac.kr
- Publication Type:Original Article
- Keywords:
Monoamine oxidase inhibitors;
MPP+;
Mitochondrial permeability transition;
Cell death;
Preventive effect
- MeSH:
1-Methyl-4-phenylpyridinium*;
Animals;
Caspase 3;
Cell Death;
Cell Survival;
Clorgyline;
Cytochromes c;
Monoamine Oxidase Inhibitors*;
Monoamine Oxidase*;
Neurons;
Oxidative Stress;
PC12 Cells;
Permeability*;
Reactive Oxygen Species;
Selegiline;
Tranylcypromine
- From:The Korean Journal of Physiology and Pharmacology
2006;10(4):207-212
- CountryRepublic of Korea
- Language:English
-
Abstract:
Mitochondrial permeability transition has been shown to be involved in neuronal cell death. Mitochondrial monoamine oxidase (MAO)-B is considered to play a part in the progress of nigrostriatal cell death. The present study examined the effect of MAO inhibitors against the toxicity of 1-methyl-4-phenylpyridinium (MPP+) in relation to the mitochondrial permeability transition. Chlorgyline (a selective inhibitor of MAO-A), deprenyl (a selective inhibitor of MAO-B) and tranylcypromine (non-selective inhibitor of MAO) all prevented cell viability loss, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH in differentiated PC12 cells treated with 500 micrometer MPP+. The MAO inhibitors at 10 micrometer revealed a maximal inhibitory effect and beyond this concentration the inhibitory effect declined. On the basis of concentration, the inhibitory potency was tranylcypromine, deprenyl and chlorgyline order. The results suggest that chlorgyline, deprenyl and tranylcypromine attenuate the toxicity of MPP+ against PC12 cells by suppressing the mitochondrial permeability transition that seems to be mediated by oxidative stress.
