[Mechanisms of mixed-function oxidase system breakdown in the hepatic endoplasmic reticulum. The role of membrane phospholipid peroxidation].

It has been shown that endogenous lipid peroxidation (LPO) is an effective mechanism participating in the destruction of endoplasmic reticulum membranes (cytochrome P450) in liver. Antioxidants are able to control the rate of degradation of cytochrome P450 in vivo. Stock of the constitutive cytochrome P450 as compared with induced P450 is more resistive to LPO in vivo and in vitro. Spontaneous as well as induced by Fe2+--ADP+ +NADPH system destruction of cytochrome P450 due to accumulation of LPO products malonic dialdehyde (MDA) occurs during incubation of isolated rats hepatocytes. The LPO inhibitors (4-methyl-2,6- ditretbutilphenol , pyrogallol) stabilize cytochrome P450 preventing accumulation MDA hepatocytes. Degradation of cytochrome P450 in microsomes during trypsin proteolysis has been found to be enhanced by PLO induction. Efficiency of proteolysis depends on the way of induction and decreases in such an order: NADPH-- HNDH --ascorbate-dependent LPO. LPO may be considered as a trigger mechanism that makes some forms of cytochrome P450 available for endogenous proteases.