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Gene specific epigenetic regulation of hepatic folate transport system is responsible for perturbed cellular folate status during aging and exogenous modulation
Author(s) -
Ahmad Najar Rauf,
Rahat Beenish,
Hussain Aashiq,
Thakur Shilpa,
Kaur Jaspreet,
Kaur Jyotdeep,
Hamid Abid
Publication year - 2016
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500991
Subject(s) - weanling , abcg2 , epigenetics , methylation , biology , dna methylation , messenger rna , transporter , endocrinology , promoter , gene expression , medicine , gene , biochemistry , atp binding cassette transporter
Scope The present study was designed to identify the molecular mechanism of folate modulation and aging on aberrant liver folate transporter system. Methods and results 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. Conclusion 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.