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.