Regulation at multiple levels control the expression of folate transporters in liver cells in conditions of ethanol exposure and folate deficiency

Abstract

Complex regulatory mechanisms control the expression of folate transporters within cells. Liver is the primary reserve of the folate stores within the body. As excessive alcohol consumption or inefficient dietary folate intake are known to create folate deficiency, so therefore the current study was designed to explore various regulatory mechanisms controlling the expression of folate transport in liver cells in conditions of ethanol exposure and folate deficiency. In order to see whether the effects mediated by the treatments are reversible or not, ethanol removal, and folate repletion was done after ethanol exposure and folate deficiency treatment respectively. Folate deficiency resulted an increase, whereas ethanol treatment decreased the folic acid uptake within the cells. The alterations in folic acid uptake were in agreement with the observed changes in the expression of folate transporters. Ethanol exposure resulted an increase in promoter methylation of reduced folate carrier; however, folate deficiency had no effect. The effects produced by ethanol exposure and folate deficiency were found to be reversible in nature as depicted in case of ethanol removal and folate repletion group. Rate of synthesis of folate transporters was found to be increased whereas half lives of mRNA of folate transporters was found to be decreased on folate deficiency treatment and reverse was the case on ethanol treatment. Overall, alteration in the expression of folate transporters under ethanol exposure and folate deficient conditions can be attributed to those regulatory mechanisms which work at the mRNA level.

Relationship between folate concentration and expression of folate-associated genes in tissue and plasma after intraoperative administration of leucovorin in patients with colorectal cancer

“…Several previous studies have shown that folate deficiency results in a significant upregulation of folate transport genes such as SLC19A1/RFC-1 and SLC46A1/PCFT [33, 34]. Folate deficiency also results in decreased half-lives of these two genes [35].…”

FASD: folic acid and formic acid — an unholy alliance in the alcohol abusing mother

“…Folate transporters in the alcohol using/abusing pregnant woman must be downregulated at the placental level. The mechanism is perhaps similar to the downregulation of folate transporters in the context of intestinal absorption of dietary folic acid (Halsted 1980;Halsted et al 2002b;Thakur and Kaur 2015).…”

“…As a result, folate deficiency is a common finding in chronic alcoholics (Axelrod and Daly 1965;Eells et al 2000a;Halsted et al 2002bHalsted et al , 2010. This malabsorption has been attributed to the downregulation of folate transporters (Halsted 1980;Halsted et al 2002b;Thakur and Kaur 2015). Folate deficiency can lead to a decrease in SAM levels (Miller et al 1994).…”