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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
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.
Folate deficiency and aging in liver decreases expression levels of reduced folate carrier (RFC) and increases expression levels of the folate exporter ABCG2 at both transcriptional and translational levels, which is further regulated by promoter hypermethylation of RFC and promoter hypomethylation of ABCG2 genes.