DIFFERENTIAL DOWN-REGULATION OF INSULIN-SENSITIVE PROTEIN-KINASE-C ISOFORMS BY 12-O-TETRADECANOYLPHORBOL-13-ACETATE IN RAT ADIPOCYTES AND BC3H-1 MYOCYTES

In rat adipocytes, chronic incubation with 12-O-tetradecanoylphorbol-13-acetate (TPA) reduced immunoreactive protein kinase-C (PKC) beta, gamma, delta, and zeta isoforms by 40-60% and PKCalpha by 75%, but had little effect on PKCepsilon levels. In BC3H-1 myocytes, chronic TPA treatment had no effect on PKCbeta, increased PKCzeta, and depleted PKCalpha. Acute treatment with insulin induced the translocation of PKCbeta in the myocytes both before and after chronic TPA treatment, but had no acute effect on the alpha or zeta isoforms. In contrast, acute TPA treatment in the myocytes had little effect on PKCbeta, but induced the rapid translocation of alpha and zeta. The differential effects of chronic TPA treatment on the down-regulation of PKCbeta may explain why insulin continues to activate biological processes in TPA-treated BC3H-1 myocytes, but not in adipocytes.