Enzymatic and nonenzymatic formation of reactive oxygen species from 6-anilino-5,8-quinolinequinone.
The nonenzymatic and enzymatic formation of reactive oxygen species (ROS) from LY83583 (6-anilino-5,8-quinolinequinone) was investigated by electron paramagnetic resonance (EPR) spectroscopy. In the presence of thiol compounds such as glutathione and L-cysteine, LY83583 underwent a one-electron reduction due to low redox potential (-0.3+/-0.01 V vs. SCE), followed by formation of LY83583 semiquinone anion radical. This species was characterized by EPR spectroscopy under an argon atmosphere at neutral pH. Under an aerobic condition, this species interacts with molecular oxygen to form a superoxide anion radical. GSH-conjugated LY83583 was also identified by NMR and FAB-MS. When LY83583 was applied to PC12 cells, ROS formation was completely inhibited by both the flavoenzyme inhibitor DPI and the DT-diaphorase inhibitor dicumarol. On the other hand, ROS generation occurred independent of intracellular GSH level. These results indicate that LY83583 can generate ROS both enzymatically and nonenzymatically, although the enzymatic formation is dominant over the nonenzymatic system in PC12 cells.
Hasegawa
Toyoshi
T
Department of Pharmacology, The University of Tokushima School of Medicine, 3-18-15 Kuramoto, 'Tokushima 770-8503, Japan.
Bando
Atsushi
A
Tsuchiya
Koichiro
K
Abe
Shinji
S
Okamoto
Masumi
M
Kirima
Kazuyoshi
K
Ueno
Satoru
S
Yoshizumi
Masanori
M
Houchi
Hitoshi
H
Tamaki
Toshiaki
T
D000634:Aminoquinolines / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003497:Cyclic N-Oxides; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis / Q000737:chemistry; D019803:Glutathione Disulfide / Q000032:analysis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010101:Oxygen Consumption; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000737:chemistry*; D019097:Spin Trapping
D000634:Aminoquinolines; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; C017245:5,5-dimethyl-1-pyrroline-1-oxide; C041715:6-anilino-5,8-quinolinedione; D005978:Glutathione; D019803:Glutathione Disulfide