Effects of various tetrahydroisoquinoline derivatives on mitochondrial respiration and the electron transfer complexes.
We report effect of various tetrahydroisoquinoline derivatives on mitochondrial respiration and the electron transfer complexes. Generally these compounds were potent inhibitors of NADH-linked mitochondrial state 3 respiration and complex I. Presence of a phenyl group at the C1 position or oxidation of N-methylated isoquinones into N-methylisoquinolinium ion augmented the potency to inhibit mitochondrial respiration and complex I. Many of these compounds have been identified in human brains. In view of the mitochondrial and oxidative stress hypothesis, our results suggest involvement of these neurotoxins as potential causes of mitochondrial failure in Parkinson's disease.
Morikawa
N
N
Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan.
Naoi
M
M
Maruyama
W
W
Ohta
S
S
Kotake
Y
Y
Kawai
H
H
Niwa
T
T
Dostert
P
P
Mizuno
Y
Y
D000818:Animals; D004579:Electron Transport / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000187:drug effects*; D009243:NAD / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects*; D019802:Succinic Acid / Q000378:metabolism
D007546:Isoquinolines; D009097:Multienzyme Complexes; D009243:NAD; D019802:Succinic Acid