Protein Kinase C Isoforms Have Differential Roles in the Regulation of Human Sebocyte Biology

Protein kinase C (PKC) isoforms have crucial roles in cutaneous signaling. Interestingly, we lack information about their involvement in human sebaceous gland biology. Therefore, in this current study, we investigated the functions of the PKC system in human immortalized SZ95 sebocytes. Using molecular biological approaches, imaging, and functional assays, we report that SZ95 sebocytes express the conventional cPKC alpha; the novel nPKC delta, epsilon, and eta; and the atypical aPKC zeta. Activation of the PKC system by phorbol 12-myristate 13-acetate (PMA) stimulated lipid synthesis (a hallmark of differentiation) and resulted in translocation and then downregulation of cPKC alpha and nPKC delta. In good accord with these findings, the effect of PMA was effectively abrogated by inhibitors and short interfering RNA-mediated "silencing" of cPKC alpha and nPKC delta. Of further importance, molecular or pharmacological inhibition of nPKC delta also prevented the lipogenic and apoptosis-promoting action of arachidonic acid. Finally, we also found that "knockdown" of the endogenous aPKC zeta activity markedly increased basal lipid synthesis and apoptosis, suggesting its constitutive activity in suppressing these processes. Collectively, our findings strongly argue for the fact that certain PKCs have pivotal, isoform-specific, differential, and antagonistic roles in the regulation of human sebaceous gland-derived sebocyte biology. Journal of Investigative Dermatology (2012) 132, 1988-1997; doi:10.1038/jid.2012.94; published online 5 April 2012