Control of Alcoholism-Related Folate Deficiency by Regulation of Urinary Folate Excretion
Abstract:
Health-related consequences of heavy drinking include nutritional deficiencies. Folate deficiency occurs from multiple causes including increased urinary folate excretion. Ethanol decreases the renal reabsorption of folate leading to increased excretion. The main aim of this research is to determine the mechanism by which ethanol decreases folate transport by the kidney. An initial objective is to determine the effects of ethanol on expression of the two renal transport proteins, the folate receptor FR and the reduced folate carrier RFC . 5 day treatment with ethanol in vitro increased the content of both transporters in cultured human proximal tubule cells. 14 day treatment of rats in vivo with ethanolcontaining diets increased the content of both transporters in isolated rat kidney membranes. This increase in transport protein content with repeated ethanol treatment may represent a way to counteract the acute ethanol-induced decrease in folate uptake in order to restore folate homeostasis. The results indicate that the long term increase in folate excretion does not result from a down-regulation of the folate transport proteins. Subsequent studies will use transport kinetic studies and pathway inactivation studies to determine which transporter is affected by ethanol.