Ethanol inhibits basic fibroblast growth factor-mediated proliferation of C6 astrocytoma cells.
Early ethanol exposure alters the proliferative activity of glial and neuronal precursors in the developing CNS. The present study tests the hypothesis that ethanol-induced alterations in cell proliferation result from interference with growth factors. An in vitro model of astroglia (C6 astrocytoma cells) was used to study the effects of ethanol on proliferation mediated by basic fibroblast growth factor (bFGF). bFGF stimulated the proliferation of C6 cells. This bFGF-enhanced proliferation was evident by increases in total cell number, DNA synthesis (as measured by [3H]thymidine incorporation), and the number of cells that took up bromodeoxyuridine. A synthetic peptide that specifically blocked the binding of bFGF to its high-affinity receptor completely abolished the proliferation-promoting effect of bFGF. The action of another mitogen for C6 cells, insulin-like growth factor-1, was not affected by this peptide. Therefore, the bFGF-stimulated proliferation was mediated through a specific bFGF receptor. Ethanol inhibited bFGF-mediated proliferation in a concentration-dependent manner. Ethanol concentrations of 100 and 200 mg/dl partially inhibited bFGF-mediated proliferation (by 58 and 74%, respectively), whereas concentrations of > or = 400 mg/dl completely abolished the growth-stimulating effect of bFGF. Our data show that ethanol alters proliferative activity of C6 cells by disrupting the action of bFGF. The target of ethanol neurotoxicity is a receptor-mediated activity. bFGF can affect cell proliferation by a non-receptor-mediated intracellular pathway, but ethanol does not have an impact on this pathway.
Luo
J
J
Department of Psychiatry, University of Iowa College of Medicine, Iowa City.
Miller
M W
MW
D000704:Analysis of Variance; D000818:Animals; D001254:Astrocytoma; D015415:Biomarkers; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis; D000431:Ethanol / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000096:biosynthesis; D007700:Kinetics; D009418:S100 Proteins / Q000032:analysis / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D004273:DNA, Neoplasm; D005904:Glial Fibrillary Acidic Protein; D009418:S100 Proteins; D016222:Fibroblast Growth Factor 2; D000431:Ethanol; D013936:Thymidine