Alcohol inhibits neurite extension and increases N-myc and c-myc proteins.
Alcohol teratogenesis may be due, in part, to inhibition of neuronal differentiation by alcohol. Because decreases in the N-myc and c-myc proteins are believed to be linked causally to neuronal differentiation, we hypothesized that alcohol would increase N-myc and c-myc proteins in undifferentiated neuronal cells and would oppose the decreases in these two proteins that normally precede differentiation. In undifferentiated LA-N-5 cultured human neuroblastoma cells, alcohol increased N-myc protein levels (178% vs. control cells) and c-myc levels (222% of control). Retinoic acid decreased N-myc and c-myc and induced neurite outgrowth (a differentiation marker). Alcohol prevented retinoic acid-elicited decreases in both myc isoforms and prevented neurite outgrowth. A significant 100% increase in c-myc and an upward trend (48%) in N-myc were observed in CA1 pyramidal neurons of the dorsal hippocampus in mouse fetuses exposed prenatally to alcohol. These data suggest that increases in N-myc and c-myc protein levels are associated with inhibition of neurite extension by alcohol.
C. S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
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DE
Saunders
C S
CS
Zajac
N L
NL
Wappler
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003864:Depression, Chemical; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000648:ultrastructure; D009447:Neuroblastoma / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002492:Central Nervous System Depressants; D016271:Proto-Oncogene Proteins c-myc; D000431:Ethanol; D014212:Tretinoin