Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-7-20
pubmed:abstractText
The functional characteristics of human proton coupled folate transporter (hPCFT)/heme carrier protein (HCP) 1 were investigated. hPCFT/HCP1 expressed transiently in human embryonic kidney 293 cells mediated the transport of folate at an acidic extracellular pH of 5.5 in a manner independent of Na(+) and insensitive to membrane potential, but its transport activity was absent at near-neutral pH. Folate transport mediated by hPCFT/hHCP1 at pH 5.5 was saturable with a K(m) of 1.67 microM and extensively inhibited by reduced folates, such as folinate, 5-methyltetrahydrofolate, and methotrexate (MTX). Sulfobro-mophthalein and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid were also found to be potent inhibitors of hPCFT/hHCP1, but hemin was found to exhibit only minimal inhibitory effect. When expressed stably as a protein fused with green fluorescent protein (GFP-hPCFT/HCP1) in MDCKII cells, GFP-hPCFT/HCP1 was mainly localized at the apical membrane, and the cellular accumulation of MTX was higher from the apical side than from the basal side. These functional features of hPCFT/HCP1 are consistent with those of the well characterized carrier-mediated folate transport system in the small intestine, suggesting that hPCFT/HCP1 is responsible for the intestinal absorption of folate and also MTX. We also found that sulfasalazine is a potent inhibitor of hPCFT/HCP1, which would interfere with the intestinal absorption of MTX when coadministered in therapy for rheumatoid arthritis as well as folate.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents..., http://linkedlifedata.com/resource/pubmed/chemical/Antirheumatic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Diclofenac, http://linkedlifedata.com/resource/pubmed/chemical/Folic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Indomethacin, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Methotrexate, http://linkedlifedata.com/resource/pubmed/chemical/Nigericin, http://linkedlifedata.com/resource/pubmed/chemical/Proton-Coupled Folate Transporter, http://linkedlifedata.com/resource/pubmed/chemical/SLC46A1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Sulfasalazine
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
322
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
469-76
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17475902-Animals, pubmed-meshheading:17475902-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:17475902-Antirheumatic Agents, pubmed-meshheading:17475902-Biological Transport, Active, pubmed-meshheading:17475902-Cell Line, pubmed-meshheading:17475902-Cell Membrane, pubmed-meshheading:17475902-Diclofenac, pubmed-meshheading:17475902-Dose-Response Relationship, Drug, pubmed-meshheading:17475902-Folic Acid, pubmed-meshheading:17475902-Green Fluorescent Proteins, pubmed-meshheading:17475902-Humans, pubmed-meshheading:17475902-Hydrogen-Ion Concentration, pubmed-meshheading:17475902-Indomethacin, pubmed-meshheading:17475902-Kinetics, pubmed-meshheading:17475902-Membrane Transport Proteins, pubmed-meshheading:17475902-Methotrexate, pubmed-meshheading:17475902-Microscopy, Confocal, pubmed-meshheading:17475902-Nigericin, pubmed-meshheading:17475902-Proton-Coupled Folate Transporter, pubmed-meshheading:17475902-Sulfasalazine, pubmed-meshheading:17475902-Transfection
pubmed:year
2007
pubmed:articleTitle
Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter.
pubmed:affiliation
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't