| Autor: |
Narakorn Khunweeraphong, Shushi Nagamori, Pattama Wiriyasermkul, Yumiko Nishinaka, Printip Wongthai, Ryuichi Ohgaki, Hidekazu Tanaka, Hideyuki Tominaga, Hiroyuki Sakurai, Yoshikatsu Kanai |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
|
| Zdroj: |
Journal of Pharmacological Sciences, Vol 119, Iss 4, Pp 368-380 (2012) |
| Druh dokumentu: |
article |
| ISSN: |
1347-8613 |
| DOI: |
10.1254/jphs.12124FP |
| Popis: |
System L is a major transport system for cellular uptake of neutral amino acids. Among system L transporters, L-type amino acid transporter 1 (LAT1) is responsible for the nutrient uptake in cancer cells, whereas L-type amino acid transporter 2 (LAT2) is a transporter for non-cancer cells. In this study, we have established HEK293 cell lines stably expressing high levels of human LAT1 and LAT2 forming heterodimers with native human 4F2hc of the cells. We have found that l-[14C]alanine is an appropriate substrate to examine the function of LAT2, whereas l-[14C]leucine is used for LAT1. By using l-[14C]alanine on LAT2, we have for the first time directly evaluated the function of human LAT2 expressed in mammalian cells and obtained its reliable kinetics. Using α-alkyl amino acids including α-methyl-alanine and α-ethyl-l-alanine, we have demonstrated that α-alkyl groups interfere with the interaction with LAT2. These cell lines with higher practical advantages would be useful for screening and analyzing compounds to develop LAT1-specific drugs that can be used for cancer diagnosis and therapeutics. The strategy that we took to establish the cell lines would also be applicable to the other heterodimeric transporters with important therapeutic implications. Keywords:: transporter, amino acid, system L, blood–brain barrier, cancer |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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