論文 - 詳細
| RRC ID | 19231 |
|---|---|
| 著者 | Shikano N, Ogura M, Sagara J, Nakajima S, Kobayashi M, Baba T, Yamaguchi N, Iwamura Y, Kubota N, Kawai K. |
| タイトル | Stimulation of 125I-3-iodo-alpha-methyl-L-tyrosine uptake in Chinese hamster ovary (CHO-K1) cells by tyrosine esters. |
| ジャーナル | Nucl Med Biol |
| Abstract |
INTRODUCTION:Transport of the amino acid analog (123)I-3-iodo-alpha-methyl-L-tyrosine, which is used in clinical SPECT imaging, occurs mainly via L-type amino acid transporter type 1 (LAT1; an amino acid exchanger). As LAT1 is highly expressed in actively proliferating tumors, we made a preliminary investigation of the effects of amino acid esters on enhancement of (125)I-3-iodo-alpha-methyl-L-tyrosine (IMT) uptake via LAT1 in Chinese hamster ovary (CHO-K1) cells. METHODS:Because the sequence of the CHO-K1 LAT1 gene is not available, we confirmed LAT1 expression through IMT (18.5 kBq) uptake mechanisms using specific inhibitors. L-Gly, L-Ser, L-Leu, L-Phe, L-Met, L-Tyr, D-Tyr, L-Val and L-Lys ethyl/methyl esters were tested in combination with IMT. Time-course studies over a 3-h period were conducted, and the concentration dependence of L-Tyr ethyl and methyl esters (0.001 to 10 mM) in combination with IMT was also examined. For a proof of de-esterification of L- and D-Tyr ethyl and methyl esters in the cells (by enzymatic attack or other cause), the concentration of L- and D-Tyr was analyzed by high-performance liquid chromatography of the esters in phosphate buffer (pH 7.4) and cell homogenates at 37 degrees C or under ice-cold conditions. RESULTS:Inhibition tests suggested that LAT1 is involved in IMT uptake by CHO-K1 cells. Co-administration of 1 mM of l-Tyr ethyl or methyl ester with IMT produced the greatest enhancement. The de-esterification reaction was stereo selective and temperature dependent in the homogenate. De-esterification kinetics were very fast in the homogenate and very slow in the phosphate buffer. CONCLUSIONS:The L-Tyr ethyl or methyl esters were the most effective enhancers of IMT uptake into CHO-K1 cells and acted by trans-stimulation of the amino acid exchange function of LAT1. This result suggests that de-esterification in the cells may be caused by enzymatic attack. We will use IMT and L-Tyr ethyl or methyl esters to examine LAT1 function in tumor cells or tissues in vivo. |
| 巻・号 | 37(2) |
| ページ | 189-96 |
| 公開日 | 2010-2-1 |
| DOI | 10.1016/j.nucmedbio.2009.10.003 |
| PII | S0969-8051(09)00243-1 |
| PMID | 20152718 |
| MeSH | Animals Biological Transport / drug effects CHO Cells Cell Extracts Cricetinae Cricetulus Esterification Esters / chemistry* Esters / metabolism Esters / pharmacology* Hydrolysis Large Neutral Amino Acid-Transporter 1 / metabolism Methyltyrosines / metabolism* |
| IF | 2.396 |
| 引用数 | 5 |
| WOS 分野 | RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING |
| リソース情報 | |
| ヒト・動物細胞 | CHO-K1(RCB0285) |