Interaction of ethanol with retinol and retinoic acid in RAR beta and GAP-43 expression.
Fetal ethanol exposure has many detrimental effects on neural development, which possibly occurs through ethanol-induced disruption of the function of vitamin A. In LAN-5 neuroblastoma cells, retinol (10(-6) M) and retinoic acid (RA; 10(-5)-10(-6) M) increased RAR beta mRNA expression. Ethanol downregulated RAR beta levels, even in the presence of retinol. RAR beta mRNA expression was decreased by ethanol in the presence of 10(-6) M RA, but not 10(-5) M RA. With cycloheximide (CX), RA still stimulated RAR beta mRNA, but the effect of ethanol was abolished. The mRNA expression of GAP-43, an important factor in neural development, increased with 10(-6) M retinol and 10(-5)-10(-9) M RA. Ethanol decreased GAP-43 mRNA expression in the presence or absence of retinol. Ethanol was without effect on GAP-43 mRNA at 10(-5) M RA, but did lower the levels at 10(-6) and 10(-7) M RA. CX prevented the effects of both RA and ethanol on GAP-43 mRNA. These studies provide support for the hypothesis that retinoid function is altered by ethanol.
Grummer
M A
MA
Department of Pediatrics, University of Wisconsin, Meriter Perinatal Center, 202 South Park Street, Madison, WI 53715, USA.
Zachman
R D
RD
D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D019922:GAP-43 Protein / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014801:Vitamin A / Q000494:pharmacology*
D019922:GAP-43 Protein; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D014801:Vitamin A; D000431:Ethanol; D014212:Tretinoin