Interaction of ethanol with retinol and retinoic acid in RAR β and GAP-43 expression

Abstract

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 β mRNA expression. Ethanol downregulated RAR β levels, even in the presence of retinol. RAR β 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 β 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.