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RFC-1 gene expression regulates folate absorption in mouse small intestine

Chiao, JH; Roy, K; Tolner, B; Yang, CH; Sirotnak, FM; (1997) RFC-1 gene expression regulates folate absorption in mouse small intestine. J BIOL CHEM , 272 (17) 11165 - 11170. Gold open access

Abstract

Mediated folate compound transport inward in isolated luminal epithelial cells from mouse small intestine was delineated as pH-dependent and non-pH-dependent components on the basis of their differential sensitivity to the stilbene inhibitor, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, pH dependence was manifested as higher maximum capacity (V-max) for influx of l,L-5-CH3-H(4)folate at acidic pH compared with neutral or alkaline pH with no effect on saturability (K-m), The pH dependent component was relatively insensitive to inhibition by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and highly saturable (K-m or K-i = 2 to 4 mu M) in the case of folic acid, folate coenzymes, and 4-aminofolate analogues as permeants or inhibitors, The non-pH-dependent component was highly sensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and poorly and variably saturable (K-m or K-i = 20 to > 2000 mu M) with respect to these folate compounds, Only the pH-dependent transport component was developmentally regulated, showing much higher maximum capacity for l,L-5-CH3-H(4)folate influx in mature absorptive rather than proliferative crypt cells, The increase in pH-dependent influx during maturation was associated with an increase in RFC-1 gene expression in the form of a 2.5-kilobase RNA transcript and 58-kDa brush-border membrane protein detected by folate-based affinity labeling and with anti-mouse RFC-1 peptide antibodies, The size of this protein was the same as that encoded by RFC-1 mRNA, The treatment of mature absorptive cells with either the affinity label or the anti RFC-1 peptide antibodies inhibited influx of l,L-[H-3]-5-CH3-H(4)folate in a concentration-dependent manner, These results strongly suggest that pH-dependent folate absorption in this tissue is regulated by RFC-1 gene expression.

Type: Article
Title: RFC-1 gene expression regulates folate absorption in mouse small intestine
Open access status: An open access publication
Publisher version: http://www.jbc.org/content/early/recent/0
Keywords: CARRIER-MEDIATED TRANSPORT, TISSUE-SPECIFIC EXPRESSION, BRUSH-BORDER MEMBRANE, ANALOG TRANSPORT, TUMOR-CELLS, MULTIPLE PROMOTERS, PROTEIN, PURIFICATION, RNA, NITROCELLULOSE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/136001
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