title: Gene specific epigenetic regulation of hepatic folate transport system is responsible for perturbed cellular folate status during aging and exogenous modulation.
abstract: The present study was designed to identify the molecular mechanism of folate modulation and aging on aberrant liver folate transporter system.
  
  
  
  An in vivo rat model was used, in which weanling, young and adult rats were given folate deficient diet for 3 and 5 months and after 3 months of folate deficiency, one group received physiological folate repletion (2 mg/kg diet) and another group received over supplemented folate diet (8 mg/kg diet) for another 2 months. In adult group, 3 and 5 months of folate deficiency decreased serum and tissue folate levels with decreased uptake of folate, further associated with decreased expression levels of reduced folate carrier (RFC) and increased expression levels of folate exporter (ABCG2) at both mRNA and protein levels, which in turn regulated by promoter hypermethylation of RFC and promoter hypomethylation of ABCG2 gene.
  
  
  
  Promoter hypermethylation of RFC and promoter hypomethylation of ABCG2 may be attributed to the down regulation of RFC and up regulation of ABCG2 at mRNA and protein levels in conditions of 3 and 5 months of folate deficiency in the adult group.
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.|Department of Biochemistry, Panjab University, Chandigarh, India.
authors.forename: Rauf
authors.initials: R
authors.lastname: Ahmad Najar
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Beenish
authors.initials: B
authors.lastname: Rahat
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
authors.forename: Aashiq
authors.initials: A
authors.lastname: Hussain
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: University Institute of Engineering and Technology, Panjab University, Chandigarh, India.
authors.forename: Jaspreet
authors.initials: J
authors.lastname: Kaur
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Jyotdeep
authors.initials: J
authors.lastname: Kaur
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.|CSIR-Academy of Scientific & Innovative Research, New Delhi, India.
authors.forename: Abid
authors.initials: A
authors.lastname: Hamid
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics / Q000378:metabolism*; D000375:Aging / Q000235:genetics*; D000818:Animals; D019175:DNA Methylation; D004032:Diet; D019587:Dietary Supplements; D044127:Epigenesis, Genetic; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood; D005494:Folic Acid Deficiency / Q000097:blood / Q000188:drug therapy; D008099:Liver / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D058978:Reduced Folate Carrier Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; C489249:Abcg2 protein, rat; D026901:Membrane Transport Proteins; D015778:Minor Histocompatibility Antigens; D058978:Reduced Folate Carrier Protein; C043408:Slc19a1 protein, rat; D005492:Folic Acid
keywords: Age; Folate deficiency; Folate over supplementation; Folate transport; Liver