UP-REGULATION OF NUCLEAR PKC AND MAP-KINASE DURING HYPERPROLIFERATIONOF GUINEA-PIG EPIDERMIS - MODULATION BY 13-(S)-HYDROXYOCTADECADIENOICACID (13-HODE)

13-(S)-Hydroxyoctadecadienoic acid (13-HODE), the lipoxygenase metabol ite of linoleic acid, has been shown to reverse the epidermal hyperpro liferation induced by topical application of docosahexaenoic acid (DNA , 22:6 n-3) on guinea pig skin. Our initial studies demonstrated that 13-HODE exerts a selective inhibition of the membrane-bound PKC-beta a ctivity in the hyperproliferative skin. To delineate the antiprolifera tive effects of 13-HODE, we investigated the nuclear events associated with this process. Our data demonstrated. that the major PKC isozymes in the epidermal nuclear fraction are alpha and zeta. Epidermal hyper proliferation induced by DHA caused an increase in nuclear total PKC a nd atypical PKC activities, and this was accompanied by an increase in the two nuclear isozymes, alpha and zeta (P < 0.05). This increase wa s reversed after topical application of 13-HODE. Similarly, 13-HODE su ppressed elevated nuclear MAP-kinase. Taken together, these data sugge st that nuclear signalling events in the epidermis involve PKC MAP-kin ase pathway. (C) 1998 Elsevier Science Inc.