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.
Saunders
D E
DE
C. S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Zajac
C S
CS
Wappler
N L
NL
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