MPP+ and MPDP+ induced oxygen radical formation with mitochondrial enzymes.
MPP+ has been reported to inhibit reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase in mitochondria, which results in the formation of O2(.-). The current report demonstrates that H2O2 and HO. are also products of MPP+ interaction with NADH dehydrogenase. It is possible that MPP. formation precedes the formation of some of these active oxygen species. Reducing equivalents for radical formation come from NADH. MPP+ may be capable of interacting with submitochondrial particles at a site other than the rotenone site, which results in some formation of oxygen radicals. Plasma amine oxidase incubations with MPDP+ resulted in O2.- H2O2, and perhaps HO. formation. This is probably due to MPP. formation from the oxidation of MPDP+. This study presents new findings that indicate the potential importance of oxygen radical formation in mitochondria during MPTP toxicity.
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90033.
J D
JD
Adams
L K
LK
Klaidman
A C
AC
Leung
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D003497:Cyclic N-Oxides; D000431:Ethanol / Q000494:pharmacology; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D008929:Mitochondria, Heart / Q000201:enzymology*; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors; D011726:Pyridinium Compounds / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D013367:Submitochondrial Particles / Q000201:enzymology
D003497:Cyclic N-Oxides; D005609:Free Radicals; D006878:Hydroxides; D011726:Pyridinium Compounds; D017382:Reactive Oxygen Species; D013113:Spin Labels; D017665:Hydroxyl Radical; D000431:Ethanol; C017245:5,5-dimethyl-1-pyrroline-1-oxide; C044755:1-methyl-4-phenyl-2,3-dihydropyridinium; D006861:Hydrogen Peroxide; D009245:NADH Dehydrogenase; D015655:1-Methyl-4-phenylpyridinium