Differential role in lipid peroxidation between rat P450 1A1 and P450 1A2.
The role of cytochrome P450 (P450) in lipid peroxidation induced by NADPH or peroxide was investigated in a reconstituted system. When cumene hydroperoxide, t-butyl hydroperoxide and hydrogen peroxide were used as initiators, the rates of malondialdehyde (MDA) formation were much higher in a reconstituted system containing P450 1A1 than those observed in a reconstituted system containing P450 1A2. In contrast to peroxide-induced lipid peroxidation, P450 1A2 catalysed NADPH-induced lipid peroxidation more effectively than did P450 1A1 regardless of the presence of ADP-Fe(NO3)3. Carbon monoxide inhibited NADPH-induced formation of MDA in a reconstituted system containing P450 1A2, but not P450 1A1. In addition, superoxide dismutase (SOD) was an effective inhibitor in a NADPH-induced lipid peroxidation system catalysed by P450 1A2 but not by P450 1A1. These results suggest that a peroxide-induced reaction might proceed readily with P450 1A1, whereas P450 1A2 mainly functions in NADPH-induced lipid peroxidation via generation of an active oxygen species. It is furthermore indicated that the difference in the effect of SOD in NADPH-induced lipid peroxidation depends on the P450 used.
Ohmori
S
S
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Misaizu
T
T
Nakamura
T
T
Takano
N
N
Kitagawa
H
H
Kitada
M
M
D000818:Animals; D001555:Benzene Derivatives; D002248:Carbon Monoxide; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006861:Hydrogen Peroxide; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008748:Methylcholanthrene; D008862:Microsomes, Liver / Q000201:enzymology*; D009249:NADP; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D013772:Tetramethylphenylenediamine
D001555:Benzene Derivatives; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D008315:Malondialdehyde; D009249:NADP; D008748:Methylcholanthrene; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D013772:Tetramethylphenylenediamine; C007164:cumene hydroperoxide