System L-amino acid transporters are differently expressed in rat astrocyte and C6 glioma cells

被引:61
作者
Kim, DK
Kim, IJ
Hwang, S
Kook, JH
Lee, MC
Shin, BA
Bae, CS
Yoon, JH
Ahn, SG
Kim, SA
Kanai, Y
Endou, H
Kim, JK
机构
[1] Chosun Univ, Coll Dent, Dept Oral Physiol, Kwangju 501759, South Korea
[2] Chonnam Natl Univ, Sch Med, Res Inst Med Sci, Kwangju 501746, South Korea
[3] Kyorin Univ, Sch Med, Dept Pharmacol & Toxicol, Tokyo 1818611, Japan
基金
新加坡国家研究基金会;
关键词
L-type amino acid transporter; astrocyte cultures; C6 glioma cells; BCH; essential amino acids; anti-cancer therapy;
D O I
10.1016/j.neures.2004.08.003
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The system L-amino acid transporter is a major nutrient transport system that is responsible for Na+-independent transport of neutral amino acids including several essential amino acids. We have compared and examined the expressions and functions of the system L-amino acid transporters in both rat astrocyte cultures and C6 glioma cells. The rat astrocyte cultures expressed the L-type amino acid transporter 2 (LAT2) with its subunit 4F2hc, whereas the L-type amino acid transporter 1 (LAT1) was not expressed in these cells. The C6 glioma cells expressed LAT1 but not LAT2 with 4F2hc. The [C-14]L-leucine uptakes by the rat astrocyte cultures and C6 glioma cells were Na+-independent and were completely inhibited by the system L selective inhibitor, BCH. These results suggest that the transport of neutral amino acids including several essential amino acids into rat astrocyte cultures and C6 glioma cells are for the most part mediated by LAT2 and LAT1, respectively. Therefore, the rat astrocyte cultures and C6 glioma cells are excellent tools for examining the properties of LAT2 and LAT1, respectively. Moreover, the specific inhibition of LAT1 in cancer cells might be a new rationale for anti-cancer therapy. (C) 2004 Published by Elsevier Ireland Ltd and the Japan Neuroscience Society.
引用
收藏
页码:437 / 446
页数:10
相关论文
共 39 条
[21]   4F2 (CD98) heavy chain is associated covalently with an amino acid transporter and controls intracellular trafficking and membrane topology of 4F2 heterodimer [J].
Nakamura, E ;
Sato, M ;
Yang, HL ;
Miyagawa, F ;
Harasaki, M ;
Tomita, K ;
Matsuoka, S ;
Noma, A ;
Iwai, K ;
Minato, N .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (05) :3009-3016
[22]   EVIDENCE FOR 2 TYPES OF MEDIATION OF NEUTRAL AMINO-ACID TRANSPORT IN EHRILICH CELLS [J].
OXENDER, DL ;
CHRISTENSEN, HN .
NATURE, 1963, 197 (486) :765-&
[23]   Functional heterodimeric amino acid transporters lacking cysteine residues involved in disulfide bond [J].
Pfeiffer, R ;
Spindler, B ;
Loffing, J ;
Skelly, PJ ;
Shoemaker, CB ;
Verrey, F .
FEBS LETTERS, 1998, 439 (1-2) :157-162
[24]   Identification of a membrane protein, LAT-2, that co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids [J].
Pineda, M ;
Fernández, E ;
Torrents, D ;
Estévez, R ;
López, C ;
Camps, M ;
Lloberas, J ;
Zorzano, A ;
Palacín, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (28) :19738-19744
[25]   Human LAT1, a subunit of system L amino acid transporter: Molecular cloning and transport function [J].
Prasad, PD ;
Wang, HP ;
Huang, W ;
Kekuda, R ;
Rajan, DP ;
Leibach, FH ;
Ganapathy, V .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 255 (02) :283-288
[26]   Cloning and functional characterization of a Na+-independent, broad-specific neutral amino acid transporter from mammalian intestine [J].
Rajan, DP ;
Kekuda, R ;
Huang, W ;
Devoe, LD ;
Leibach, FH ;
Prasad, PD ;
Ganapathy, V .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2000, 1463 (01) :6-14
[27]   LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine [J].
Rossier, G ;
Meier, C ;
Bauch, C ;
Summa, V ;
Sordat, B ;
Verrey, F ;
Kühn, LC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (49) :34948-34954
[28]  
SANG JS, 1995, CANCER RES, V55, P1152
[29]   Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity [J].
Segawa, H ;
Fukasawa, Y ;
Miyamoto, K ;
Takeda, E ;
Endou, H ;
Kanai, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (28) :19745-19751
[30]   Cloning and functional expression of a human Na+ and Cl--dependent neutral and cationic amino acid transporter B0+ [J].
Sloan, JL ;
Mager, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (34) :23740-23745