Effects of Oxidative Stress on Dopaminergic Neurotoxicity

Keimyung Medical Journal 2005;24(2):146-155.

도파민성 신경독성에서 산화스트레스의 역할

강병준; 김준철; 여주천; 정종희; 박원균

Abstract

MPTP (1-methyl-4-phenyl-1;2;3;6-tetrahydropyridine) and its metabolite MPP+ (1-methyl-4-phenyl pyridium) are specific dopaminergic neurotoxins and induce parkisonism-like symptoms and signs in animal models. This study was designed to evaluate the effect of oxidative stress on MPP+ -induced dopaminergic toxicity and the protective effects of antioxidants. PC12 cells were exposed to the dopaminergic neurotoxicity by adding 0.05-10 mM MPP+ for 1-24 hrs. In the cells treated with 2 mM MPP+; cell number decreased and the neurites were markedly withdrawal and the cell viability decreased almost 50%. Nerve growth factor (NGF)-differentiated PC12 cells showed higher viabilities than untreated PC12 cells in 0.1-10 mM MPP+. N-acetyl cysteine (NAC; 0.1-10 mM) showed significant protective effects against the dopaminergic cytotoxicity with 2 mM MPP+; and led to almost complete recovery to normal cells over 3 mM NAC. L-2-oxothiazoline-4-carboxylate (OTC; 0.1-2 mM) showed slightly increased the viability of PC12 cells against the dopaminergic toxicity with 2 mM MPP+. however there was not a significant recovery comparing with normal cells. L-lipoic acid (0.1-2 mM) showed some protective effects on PC12 cells against thd dopaminergic cytotoxicity with 2 mM MPP+; however they did not show a significant recovery comparing with normal PC12 eclls. In conclusion; it seems that oxidative stress participates as an important mechanism in MPP+-include dopaminergic neurotoxicity nad NAC may be a good neuroprotective agent against MPP+ -induced dopaminergic neurotoxicity.

Key Words: Antioxidants, Dopaminergic neurotoxicity, MPP+, Oxidative stress