Functional characterization of human organic cation transporter OCTN1: single nucleotide polymorphisms in the Japanese population
スポンサーリンク
概要
- 論文の詳細を見る
The organic cation transporter OCTN1 (SLC22A4) is expressed ubiquitously, with strong expression in kidney, trachea, bone marrow, and fetal liver, and it mediates transport of organic cations in a pH-dependent manner. Recent studies have identified single nucleotide polymorphisms (SNPs) of OCTN1 in the Japanese population. Two SNPs present in the exon regions, c1063t and g1531a, cause amino acid mutation, Thr306Ile (T306I) and Gly462Glu (G462E), respectively. We examined the influence of these SNPs on the intracellular localization, protein expression, and transport activity of OCTN1. Immunocytochemical analysis showed similar localizations of OCTN1 in cellular membranes of HEK293 cells transiently transfected with an expression plasmid DNA for OCTN1 or its SNP allelic variants. The Km and Vmax values for tetraethylammonium (TEA) uptake by T306I were similar to those of the wild-type even when the Vmax value was normalized for the expression level of OCTN1 protein. In contrast, G462E had almost negligible transport activity, although the protein expression level of G462E was equivalent to that of the wild-type. We conclude that the SNP that causes the single amino acid mutation T306I does not affect TEA transport activity, whereas the mutation G462E abrogates the TEA transport activity, presumably affecting the physiological function of OCTN1 and/or the pharmacological characteristics of its substrates. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association.
- Wiley-Blackwellの論文
- 2004-12-00
Wiley-Blackwell | 論文
- Follicular dendritic cell sarcoma of small intestine with aberrant T-cell marker expression
- Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma
- Running Test of VVVF Inverter Type Railcar Using Lithium Ion Battery
- Inhibitory effects of epigallocatechin-3 gallate, a polyphenol in green tea, on tumor-associated endothelial cells and endothelial progenitor cells
- Palmitoylation of the sphingosine 1-phosphate receptor S1P1 is involved in its signaling functions and internalization