Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells.

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Ashokkumar B, Mohammed ZM, Vaziri ND, Said HM

Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells.

Am J Clin Nutr. 2007 Jul;86(1):159-66.

PubMed ID

17616776 [ View in PubMed

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Abstract

BACKGROUND: Folic acid [corrected] plays an essential role in cellular metabolism. Its deficiency can lead to neural tube defects. However, optimization of body folate homeostasis can reduce the incidence of neural tube defects and may decrease the risk of Alzheimer and cardiovascular diseases and cancer. Hence, food fortification and intake of supplemental folate are widespread. OBJECTIVE: We examined the effects of long-term folate oversupplementation on the physiologic markers of intestinal and renal folate uptake processes. DESIGN: Human-derived intestinal Caco-2 and renal HK-2 epithelial cells were maintained (5 generations) in a growth medium oversupplemented (100 micromol folic acid/L) or maintained under sufficient conditions (0.25 and 9 micromol folic acid/L). RESULTS: Carrier-mediated uptake of (3)H-folic acid (2 micromol/L) at buffer pH 5.5 (but not buffer pH 7.4) by Caco-2 and HK-2 cells maintained under the folate-oversupplemented condition was significantly (P<0.01) and specifically lower than in cells maintained under the folate-sufficient condition. This reduction in folic acid uptake was associated with a significant decrease in the protein and mRNA levels of the human reduced-folate carrier (hRFC) and a decrease in the activity of the hRFC promoter. It was also associated with a decrease in mRNA levels of the proton-coupled folate transporter/heme carrier protein 1 (PCFT/HCP1) and folate receptor (FR). CONCLUSIONS: Long-term oversupplementation with folate leads to a specific and significant down-regulation in intestinal and renal folate uptake, which is associated with a decrease in message levels of hRFC, PCFT/HCP1, and FR. This regulation appears to be mediated via a transcriptional mechanism, at least for the hRFC system.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Folic acid	Proton-coupled folate transporter	Protein	Humans	Unknown	Substrate	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Folic acid	Approved Nutraceutical Vet Approved	FOLR1	2348	downregulated	Folic Acid results in decreased expression of FOLR1 mRNA	11q13.4
Folic acid	Approved Nutraceutical Vet Approved	FOLR2	2350	downregulated	Folic Acid results in decreased expression of FOLR2 mRNA	11q13.4
Folic acid	Approved Nutraceutical Vet Approved	SLC19A1	6573	downregulated	Folic Acid results in decreased expression of SLC19A1 mRNA	21q22.3
Folic acid	Approved Nutraceutical Vet Approved	SLC46A1	113235	downregulated	Folic Acid results in decreased expression of SLC46A1 mRNA	17q11.2