Radical formation site of cerebral complex I and Parkinson's disease.
Paraquat was reduced to the paraquat radical via complex I in bovine cerebral mitochondria and accelerated lipid peroxidation. Thirty-kilodalton subunit of complex I was considered to be the radical formation site, because of its marked destruction by the paraquat radical. The lipid peroxidation by the paraquat radical was suppressed not only by superoxide dismutase (SOD) but also by mannitol. The destruction of complex I subunits via lipid peroxidation must have been caused by the hydroxyl radical which was formed from the superoxide radical. The same phenomenon was observed by using 1-methylnicotinamide (MNA), which contains the same partial structure as paraquat in itself and is metabolized from nicotinamide in a living body. We observed NADH oxidation by MNA via cerebral complex I (Km = 26.3 mM), and MNA destroyed some complex I subunits, especially 30-kilodalton protein. Paraquat might be useful for studying the pathogenesis of Parkinson's disease (PD) in vitro, and MNA is expected to be one of the causal substances of PD from the viewpoint of the oxidative stress theory.
Fukushima
T
T
Department of Environmental Medicine, Shimane Medical University, Izumo, Japan.
Tawara
T
T
Isobe
A
A
Hojo
N
N
Shiwaku
K
K
Yamane
Y
Y
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000302:isolation & purification / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010269:Paraquat / Q000633:toxicity; D010300:Parkinson Disease / Q000201:enzymology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D017382:Reactive Oxygen Species; D009243:NAD; D013481:Superoxides; D009536:Niacinamide; D017665:Hydroxyl Radical; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); D010269:Paraquat; C024058:N(1)-methylnicotinamide