Protein kinase C in the developing kidney: isoform expression and effects of ceramide and PKC inhibitors.

Protein kinase C (PKC) is a serine/threonine kinase recognized as a key enzyme in signal transduction mechanisms in various biological processes. During development, PKC is involved in the regulation of growth and differentiation. In mature tissue PKC is important for homeostatic functions. We studied PKC with regard to expression and effects on differentiation, growth and apoptosis in the developing kidney. Using in situ hybridization, we demonstrate age-dependent expression of PKC alpha, PKC delta, PKC zeta and PKC lambda during fetal and postnatal kidney development. The endogenous sphingolipid product ceramide, as well as specific PKC inhibitors, disturbed nephron formation and induced apoptosis in organ cultures of E13 kidneys. In primary cell cultures of proximal tubule cells, ceramide and the specific PKC inhibitors induced apoptosis. In conclusion, PKC alpha, PKC delta, PKC zeta and PKC lambda are expressed in an age-dependent pattern during kidney development. Inhibition of PKC disturbs nephron formation, inhibits growth and induces apoptosis in the developing kidney. The findings suggest that PKC plays an important role in regulating normal kidney growth and differentiation.