The role of secondary messengers in the regulation of lipid peroxidation in rat liver microsomes.

The effect of phorbol-12-myristate-13-acetate (PMA), an activator of protein kinase C (PK-C) on lipid peroxidation (LPO) in rat liver homogenates and microsomes was studied. PMA (10(-10) to 10(-6) M) produced a concentration-dependent inhibition of LPO, which was greatly decreased by polymyxin B (PxB) (an inhibitor of PK-C). The non-active analogue of PMA, 4 alpha-phorbol-12,13-didecanoate (4 alpha-PDD) exerted no inhibitory effect. The adenylate cyclase activator, forskolin (FK) (10(-6) M) abolished the inhibitory effect of PMA on LPO. PMA and FK did not inhibit LPO in liposomes. It is suggested that LPO in biomembranes could be regulated by PK-C, whose inhibitory effect might be prevented by cAMP-dependent protein kinases.