Possible role of 1-methylnicotinamide in the pathogenesis of Parkinson's disease.
This study tested the hypothesis, that nicotinamide N-methyltransferase (NAMT) activity in the brain could convert nicotinamide to 1-methylnicotinamide (MNA) and by that means damage the nigro-neostriatal dopaminergic neurons. The NAMT activities of rat brain and liver were assayed with gas chromatographic-mass spectrometric analysis in a selected ion monitoring system. They amounted to 0.30 nmol/mg x h and 0.51 nmol/mg x h, respectively. The MNA injection in rat substantia nigra pars compacta significantly decreased dopamine content in the striatum. NADH oxidation and lipid peroxidation by MNA via rat brain submitochondrial particles (SMP) under the condition of pH ranging from pH 6.0 to 10.0 were verified. The pH optimum for the NADH oxidation was 9.0. The pH optimum for the peroxidation of the lipid composing SMP by MNA was also 9.0. The lipid peroxidation in this assay was suppressed by superoxide dismutase. The superoxide anion formed by MNA via mitochondria might be involved in the etiology of Parkinson's disease.
Fukushima
Tetsuhito
T
Department of Public Health, School of Medicine, Fukuoka University, Japan. t-fuku@fukuoka-u.ac.jp
Kaetsu
Akihiko
A
Lim
Heejin
H
Moriyama
Masaki
M
D000818:Animals; D001921:Brain / Q000201:enzymology; D002458:Cell Fractionation; D003600:Cytosol / Q000201:enzymology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D006863:Hydrogen-Ion Concentration; D007267:Injections; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D050903:Nicotinamide N-Methyltransferase; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D009536:Niacinamide; D009245:NADH Dehydrogenase; D008780:Methyltransferases; D050903:Nicotinamide N-Methyltransferase; C024058:N(1)-methylnicotinamide; D004298:Dopamine