PROTEIN-KINASE-C AND MOUSE SCIATIC-NERVE REGENERATION

We have studied the role of protein kinase C (PKC) in peripheral nerve regeneration by using the cultured adult mouse sciatic nerve, which d isplays regrowth of sensory axons under serum-free conditions. By the use of immunohistochemistry we show that one of the isoforms of PKC, P KC beta, is present in the nerve cell bodies of normal nerves and is u pregulated after injury. In spite of this, the specific PKC inhibitor chelerythrine at 5 mu M, a concentration well above its IC50 value for PKC, failed to reduce the outgrowth distance of new axons. This was n ot due to impermeability of the drug, since the same concentration cau sed a clear reduction of the injury-induced proliferation of Schwann c ells in the crush region. Likewise, HA-1004, an inhibitor of cyclic nu cleotide-dependent protein kinases, also lacked effect on outgrowth wh en used on its own, even at very high concentrations (100 mu M). In co ntrast, outgrowth was significantly reduced when 5 mu M chelerythrine and 5 mu M HA-1004 were used in combination. In conclusion, the presen t results suggest that PKC-activity is important but not indispensable for the regeneration process. Successful completion of the latter cou ld be achieved by several, perhaps redundant, phosphorylation systems.