Protein kinase C inhibitors enhance the synergistic mitogenic effects of ethanolamine analogues and insulin in NIH 3T3 fibroblasts.
Monomethylethanolamine (1 mM) and dimethylethanolamine (1 mM) stimulated DNA synthesis 10- and 15-fold, respectively, in NIH 3T3 fibroblasts. In addition, simultaneous treatments with insulin (500 nM) and methylated ethanolamine analogues (1 mM or less) resulted in synergistic activation of DNA synthesis. The order of mitogenic potency of ethanolamine analogues was dimethylethanolamine > monomethylethanolamine > ethanolamine. 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 analogues, choline and insulin were considerably (1.7- to 1.9-fold) enhanced by GF 109203X (3 microM), a specific inhibitor of protein kinase C. The results suggest that ethanolamine analogues enhance insulin-induced DNA synthesis by a mechanism which is inhibited by the protein kinase C system.
Kiss
Z
Z
Hormel Institute, University of Minnesota, Austin 55912, USA.
Crilly
K S
KS
Anderson
W B
WB
D016475:3T3 Cells; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000008:administration & dosage; D000818:Animals; D002794:Choline / Q000008:administration & dosage; D004247:DNA / Q000096:biosynthesis; D003642:Deanol / Q000008:administration & dosage; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D004983:Ethanolamines / Q000008:administration & dosage* / Q000378:metabolism; D007211:Indoles / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage*; D008301:Maleimides / Q000008:administration & dosage; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D004983:Ethanolamines; D007211:Indoles; D007328:Insulin; D008301:Maleimides; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003642:Deanol; D004247:DNA; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D002794:Choline