In order to delineate the biochemical events in the nuclear compartment of
an in vivo proliferating epidermis, we produced a model of hyperproliferati
ve epidermis by topical application of docosahexaenoic acid (22:6n-3) on gu
inea pig skin. Employing this model we demonstrated: (i) that protein kinas
e C (PKC)-alpha and atypical PKC-zeta are the two major PKC isozymes in the
normal epidermal nuclear membrane, in contrast to PKC-alpha and PKC-beta i
n the epidermal plasma membrane; (ii) that topical application of docosahex
aenoic acid induced epidermal hyperproliferation and enhanced total nuclear
PKC, particularly nuclear PKC-alpha and the atypical PKC-zeta isozymes. Th
e 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 upregulati
on of nuclear PKC/mitogen-activated protein-kinase signaling pathway.