Kim Do Kyung, Kim In Jin, Hwang Shinae, Kook Ji Hyun, Lee Min-Cheol, Shin Boo Ahn, Bae Choon Sang, Yoon Jung Hoon, Ahn Sang Gun, Kim Soo A, Kanai Yoshikatsu, Endou Hitoshi, Kim Jong-Keun
Department of Oral Physiology, Chosun University College of Dentistry, 375 Seosuk-dong, Dong-gu, Gwangju, 501-759, South Korea.
Neurosci Res. 2004 Dec;50(4):437-46. doi: 10.1016/j.neures.2004.08.003.
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 [14C]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.
L-氨基酸转运系统是一种主要的营养物质转运系统,负责对包括几种必需氨基酸在内的中性氨基酸进行不依赖于钠离子的转运。我们已经比较并研究了L-氨基酸转运系统在大鼠星形胶质细胞培养物和C6胶质瘤细胞中的表达及功能。大鼠星形胶质细胞培养物表达l型氨基酸转运体2(LAT2)及其亚基4F2hc,而l型氨基酸转运体1(LAT1)在这些细胞中不表达。C6胶质瘤细胞表达LAT1,但不表达LAT2及其4F2hc。大鼠星形胶质细胞培养物和C6胶质瘤细胞对[14C]l-亮氨酸的摄取不依赖于钠离子,并被l型选择性抑制剂BCH完全抑制。这些结果表明,包括几种必需氨基酸在内的中性氨基酸进入大鼠星形胶质细胞培养物和C6胶质瘤细胞的转运在很大程度上分别由LAT2和LAT1介导。因此,大鼠星形胶质细胞培养物和C6胶质瘤细胞分别是研究LAT2和LAT1特性的优良工具。此外,对癌细胞中LAT1的特异性抑制可能是抗癌治疗的一个新的理论依据。