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.
Adams
J D
JD
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90033.
Klaidman
L K
LK
Leung
A C
AC
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