title: Increased synthesis of folate transporters regulates folate transport in conditions of ethanol exposure and folate deficiency.
abstract: Excessive alcohol consumption and dietary folate inadequacy are the main contributors leading to folate deficiency (FD). The present study was planned to study regulation of folate transport in conditions of FD and ethanol exposure in human embryonic kidney cell line. Also, the reversible nature of effects mediated by ethanol exposure and FD was determined by folate repletion and ethanol removal. For ethanol treatment, HEK293 cells were grown in medium containing 100 mM ethanol, and after treatment, one group of cells was shifted on medium that was free from ethanol. For FD treatment, cells were grown in folate-deficient medium followed by shifting of one group of cells on folate containing medium. FD as well as ethanol exposure resulted in an increase in folate uptake which was due to an increase in expression of folate transporters, i.e., reduced folate carrier, proton-coupled folate transporter, and folate receptor, both at the mRNA and protein level. The effects mediated by ethanol exposure and FD were reversible on removal of treatment. Promoter region methylation of folate transporters remained unaffected after FD and ethanol exposure. As far as transcription rate of folate transporters is concerned, an increase in rate of synthesis was observed in both ethanol exposure and FD conditions. Additionally, mRNA life of folate transporters was observed to be reduced by FD. An increased expression of folate transporters under ethanol exposure and FD conditions can be attributed to enhanced rate of synthesis of folate transporters.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Thakur
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Deepti
authors.initials: D
authors.lastname: More
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Beenish
authors.initials: B
authors.lastname: Rahat
authors.affiliation: Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Krishan Lal
authors.initials: KL
authors.lastname: Khanduja
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India. jyotdeep2001@yahoo.co.in.
authors.forename: Jyotdeep
authors.initials: J
authors.lastname: Kaur
mesh_terms: D000431:Ethanol / Q000008:administration & dosage*; D005492:Folic Acid / Q000378:metabolism*; D005494:Folic Acid Deficiency / Q000378:metabolism*; D058972:Folic Acid Transporters / Q000096:biosynthesis*; D057809:HEK293 Cells; D006801:Humans
chemical_list: D058972:Folic Acid Transporters; D000431:Ethanol; D005492:Folic Acid
keywords: Ethanol exposure; Folate deficiency; Folate transport; Folate transporters; HEK293 cells; Regulatory mechanisms