1-Methyl-4-phenylpyridinium (MPP+) induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in bovine heart submitochondrial particles.
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.
Hasegawa
E
E
Department of Neurology, University of Occupational and Environmental Health, Kitakyushu, Japan.
Takeshige
K
K
Oishi
T
T
Murai
Y
Y
Minakami
S
S
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D005609:Free Radicals; D015227:Lipid Peroxidation / Q000187:drug effects*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000494:pharmacology; D013367:Submitochondrial Particles / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D005609:Free Radicals; D009243:NAD; D013481:Superoxides; D015655:1-Methyl-4-phenylpyridinium