Upregulation of Nuclear PKC and MAP-Kinase During Hyperproliferation of Guinea Pig Epidermis: Modulation by 13-(S)-Hydroxyoctadecadienoic Acid (13-HODE)

13-(S)-Hydroxyoctadecadienoic acid (13-HODE), the lipoxygenase metabolite of linoleic acid, has been shown to reverse the epidermal hyperproliferation 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-β activity in the hyperproliferative skin. To delineate the antiproliferative 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 α and ζ. Epidermal hyperproliferation induced by DHA caused an increase in nuclear total PKC and atypical PKC activities, and this was accompanied by an increase in the two nuclear isozymes, α and ζ ( P < 0.05). This increase was reversed after topical application of 13-HODE. Similarly, 13-HODE suppressed elevated nuclear MAP-kinase. Taken together, these data suggest that nuclear signalling events in the epidermis involve PKC-MAP-kinase pathway.