1-METHYL-4-PHENYLPYRIDINIUM (MPP+) INDUCES NADH-DEPENDENT SUPEROXIDE FORMATION AND ENHANCES NADH-DEPENDENT LIPID-PEROXIDATION IN BOVINE HEART SUBMITOCHONDRIAL PARTICLES

被引:319
作者
HASEGAWA, E [1 ]
TAKESHIGE, K [1 ]
OISHI, T [1 ]
MURAI, Y [1 ]
MINAKAMI, S [1 ]
机构
[1] KYUSHU UNIV,SCH MED,DEPT BIOCHEM,FUKUOKA 812,JAPAN
关键词
D O I
10.1016/0006-291X(90)90498-C
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We studied the effects of 1-methyl-4-phenylpyridinium (MPP+), a metabolite of a parkinsonism-inducing drug, on the superoxide formation and the lipid peroxidation in bovine heart submitochondrial particles. The NADH-supported formation of superoxide radicals was induced by MPP+ at the concentration which is considered to exist in mitochondria of dopamine neurons. The formation increased as the NADH-ubiquinone reductase activity was inhibited by MPP+. The NADH-supported lipid peroxidation by the particles in the presence of ADP-Fe3+ chelate was also enhanced by MPP+ at similar concentrations. The formation was inhibited by succinate and the reduction of endogenous ubiquinone seems to be related to the inhibition. A possibility was discussed that the formation of superoxide anions and the lipid peroxidation may contribute in the cytotoxicity of the drug. © 1990.
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页码:1049 / 1055
页数:7
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