Reversal of alcohol's effects on neurite extension and on neuronal GAP43/B50, N-myc, and c-myc protein levels by retinoic acid.
Alcohol teratogenesis may be due in part to inhibition of neuronal differentiation by ethanol. We showed previously that alcohol decreased neuronal differentiation (neurite extension) and increased N-myc and c-myc neuronal protein levels. Since Growth-Associated Protein 43 (GAP43/B50) levels must increase for neurons to differentiate, alcohol may decrease GAP43/B50. Alcohol dose-dependently (0-0.5%) decreased GAP43/B50 protein levels by up to 92% in immature LA-N-5 cells. Five nM retinoic acid alone induced differentiation and increased GAP43/B50 levels to 230% of control. These retinoic acid-induced increases in GAP43/B50 and neurite outgrowth, and decreases in N-myc and c-myc, were reversed dose-dependently by alcohol (0-0.5%). Conversely, the adverse effects of 0.25% alcohol on neurite extension, GAP43/B50, N-myc, and c-myc were prevented by 15 and 45 nM retinoic acid. These results suggest that inhibition of neuronal differentiation by alcohol and prevention of such effects by retinoic acid are related to changes in GAP43/B50, N-myc and c-myc.
Saunders
D E
DE
Fetal Alcohol Research Center, C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecoloy, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Hannigan
J H
JH
Zajac
C S
CS
Wappler
N L
NL
D002454:Cell Differentiation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D019922:GAP-43 Protein; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D019922:GAP-43 Protein; D006133:Growth Substances; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016271:Proto-Oncogene Proteins c-myc; D000431:Ethanol; D014212:Tretinoin