Inhibition of N-acetylaspartate production: implications for 1H MRS studies in vivo.
The effect of specific irreversible inhibitors of complexes I, III, IV and V of the mitochondrial respiratory chain, (rotenone, myxothiazol, cyanide and oligomycin, respectively) on mitochondrial N-acetylaspartate production, and its relationship to oxidative phosphorylation (ATP production and oxygen consumption) were investigated in isolated rat brain mitochondria. Mitochondrial N-acetylaspartate production, ATP production and oxygen consumption were all significantly decreased in the presence of each of the inhibitors used compared with control incubations, and correlated positively with each other. It is postulated that decreased N-acetylaspartate levels seen in disease states by 1H NMR spectroscopy in vivo may reflect primarily an impaired mitochondrial energy production rather than neuronal cell loss.
Bates
T E
TE
Department of Neurochemistry, Institute of Neurology, University of London, Queen Square, England.
Strangward
M
M
Keelan
J
J
Davey
G P
GP
Munro
P M
PM
Clark
J B
JB
D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004579:Electron Transport / Q000187:drug effects*; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D011522:Protons; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D011522:Protons; D001224:Aspartic Acid; C000179:N-acetylaspartate; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D006180:Proton-Translocating ATPases; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III