PROTEIN-KINASE-C INHIBITORS ENHANCE THE SYNERGISTIC MITOGENIC EFFECTSOF ETHANOLAMINE ANALOGS AND INSULIN IN NIH 3T3 FIBROBLASTS

Monomethylethanolamine (1 mM) and dimethylethanolamine (1 mM) stimulat ed DNA synthesis 10- and 15-fold, respectively, in NIH 3T3 fibroblasts . In addition, simultaneous treatments with insulin (500nM)and methyla ted ethanolamine analogues (1 mM or less) resulted in synergistic acti vation of DNA synthesis. The order of mitogenic potency of ethanolamin e analogues was dimethylethanolamine > monomethylethanolamine > ethano lamine. Choline (1-5 mM) alone had no effect on DNA synthesis, but it increased the combined effects of lower concentrations of ethanolamine analogues and insulin. The synergistic effects of ethanolamine analog ues, choline and insulin were considerably (1.7- to 1.9-fold) enhanced by GF 109203X (3 mu M), a specific inhibitor of protein kinase C. The results suggest that ethanolamine analogues enhance insulin-induced D NA synthesis by a mechanism which is inhibited by the protein kinase C system. (C) 1996 Academic Press, Inc.