Scope: The study was designed to identify the regulatory mechanisms underlying the effects of ethanol exposure on intestinal folate transport and to investigate the reversibility of such effects.
Methods and results: Caco-2 cells were grown in control and ethanol containing medium for 96 h. Thereafter, one subgroup of cells was shifted on ethanol free medium and grown for next 72 h. For in vivo studies, rats were given 1g ethanol/kg body weight/day either for 3 or 5 months and after 3 months of ethanol treatment, one group of rats received no ethanol for 2 months. A significant decrease in folic acid transport as well as expression of folate transporters was observed on ethanol treatment and the effects were reversible upon removal of ethanol. Ethanol exposure had no impact on CpG island methylation of the folate transporters however, an increase in their mRNA half-life was observed that seems to be a homeostatic mechanism. Chromatin immunoprecipitation assay revealed a decrease in binding of SP1 transcription factor to the promoter regions of folate transporters.
Conclusion: Reduced binding of SP1 to the promoter region of folate transporters may be a part of the regulatory mechanism resulting in decreased expression of folate transporters on ethanol exposure.
Keywords: Caco-2 cells; Ethanol treatment; Folate transport; Intestine; Regulatory mechanisms.
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