Ethanol enhances growth factor-induced neurite formation in PC12 cells.
Ethanol can injure the nervous system by disturbing the growth of neural processes. PC12 cells, which form neurites in response to nerve growth factor (NGF), fibroblast growth factor (FGF), and cAMP analogues, were used to study mechanisms by which ethanol alters process outgrowth. Ethanol potentiated NGF-induced neurite outgrowth in cells cultured on different substrata and in serum-containing or defined medium. Ethanol did not increase NGF receptor binding or internalization of NGF. Neurite outgrowth induced by basic FGF was also increased by ethanol but outgrowth induced by forskolin was not. Ethanol potentiated NGF-induced expression of Thy-1, but not of neural cell adhesion molecule (N-CAM), indicating that some, but not all actions of NGF are enhanced by ethanol. In some brain regions, chronic exposure to ethanol increases the growth of dendrites. This has been explained as a compensatory response of surviving neurons to the loss of neighboring cells, and not as a direct effect of ethanol. The present findings suggest that, in some cells, ethanol directly promotes growth factor-mediated neurite formation. This could harm the nervous system by disturbing the balanced development and organization of synapses.
Department of Neurology, Ernest Gallo Clinic and Research Center, University of California, San Francisco General Hospital 94110.
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Messing
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Henteleff
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Park
D000438:Alcohols / Q000494:pharmacology; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003470:Culture Media; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000032:analysis; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000032:analysis; D016501:Neurites / Q000187:drug effects*; D016716:PC12 Cells; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism; D018800:Thy-1 Antigens
D000438:Alcohols; D000954:Antigens, Surface; D015816:Cell Adhesion Molecules, Neuronal; D003470:Culture Media; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D018800:Thy-1 Antigens; D005576:Colforsin; D000431:Ethanol; D005346:Fibroblast Growth Factors