Evidence of nuclear PKC/MAP-kinase cascade in guinea pig model of epidermal hyperproliferation

In order to delineate the biochemical events in the nuclear compartment of an in vivo proliferating epidermis, we produced a model of hyperproliferative epidermis by topical application of docosahexaenoic acid (22:6n-3) on guinea pig skin. Employing this model we demonstrated: (i) that protein kinase C (PKC)-a and atypical PKC-zeta are the two major PKC isozymes in the normal epidermal nuclear membrane, in contrast to PKC-alpha and PKC-beta in the epidermal plasma membrane; (ii) that topical application of docosahexaenoic acid induced epidermal hyperproliferation and enhanced total nuclear PKC, particularly nuclear PKC-alpha and the atypical PKC-zeta isozymes. The increase in the nuclear PKC isozymes paralleled a marked increase in the expression of nuclear mitogen-activated protein-kinase. These data suggest that epidermal hyperproliferative activity is accompanied by the upregulation of nuclear PKC/mitogen-activated protein-kinase signaling pathway.