Form-specific degradation of cytochrome P-450 by lipid peroxidation in rat liver microsomes.
Microsomal lipid peroxidation caused decreases in the activities of ethylmorphine N-demethylase and testosterone 6 beta-hydroxylase more markedly than aniline hydroxylase, p-phenetidine O-deethylase and testosterone 2 alpha- and 16 alpha-hydroxylases. Results of sodium dodecylsulfate-polyacrylamide gel electrophoresis of liver microsomes showed that proteins with molecular weights between 47kDa and 50kDa in liver microsomes were sensitively degraded by lipid peroxidation. Western-blot analysis of liver microsomes with antibodies to P-448-H, P-450 male and P-450 PB-1 which corresponded to P-450d, P-450h and P-450 PCN, respectively, showed that the amount of P-450 PB-1 was decreased more markedly by lipid peroxidation as compared to those of P-450 male and P-448-H. It seemed, therefore, likely that the stability of cytochrome P-450 to lipid peroxidation varies dependent on the forms of cytochrome P-450.
Kitada
M
M
Division of Analytical Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Komori
M
M
Ohi
H
H
Imaoka
S
S
Funae
Y
Y
Kamataki
T
T
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000378:metabolism
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C022724:testosterone 7-alpha-hydroxylase, hamster