title: 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.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Thakur
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Jyotdeep
authors.initials: J
authors.lastname: Kaur
mesh_terms: D001681:Biological Assay; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D058975:Folate Receptor 1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000494:pharmacology*; D005494:Folic Acid Deficiency / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D007780:Lacticaseibacillus casei / Q000254:growth & development / Q000378:metabolism; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D058979:Proton-Coupled Folate Transporter / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D058978:Reduced Folate Carrier Protein / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014316:Tritium
chemical_list: D058975:Folate Receptor 1; D058979:Proton-Coupled Folate Transporter; D012333:RNA, Messenger; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; C505058:SLC46A1 protein, human; D014316:Tritium; D000431:Ethanol; D005492:Folic Acid
keywords: HepG2 cells; ethanol exposure; folate deficiency; folate transporters; folic acid; regulatory mechanisms