http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Kanai, Yoshikatsu,Endou, Hitoshi The Korean Society of Pharmacology 2004 The Korean Journal of Physiology & Pharmacology Vol.8 No.3
The heterodimeric amino acid transporter family is a subfamily of SLC7 solute transporter family which includes 14-transmembrane cationic amino acid transporters and 12-transmembrane heterodimeric amino acid transporters. The members of heterodimeric amino acid transporter family are linked via a disulfide bond to single membrane spanning glycoproteins such as 4F2hc (4F2 heavy chain) and rBAT $(related\;to\;b^0,\;^+-amino\;acid\;transporter)$. Six members are associated with 4F2hc and one is linked to rBAT. Two additional members were identified as ones associated with unknown heavy chains. The members of heterodimeric amino acid transporter family exhibit diverse substrate selectivity and are expressed in variety of tissues. They play variety of physiological roles including epithelial transport of amino acids as well as the roles to provide cells in general with amino acids for cellular nutrition. The dysfunction or hyperfunction of the members of the heterodimeric amino acid transporter family are involved in some diseases and pathologic conditions. The genetic defects of the renal and intestinal transporters $b^{0,+}AT/BAT1\;(b^{0,+}-type\;amino\;acid\;transporter/b^{0,+}-type\;amino\;acid\;transporter\;1)$ and $y^+LAT1\;(y^+L-type\;amino\;acid\;transporter\;1)$ result in the amino aciduria with sever clinical symptoms such as cystinuria and lysin uric protein intolerance, respectively. LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x-C-type transporter) functions to protect cells against oxidative stress, while its over-function may be damaging neurons leading to the exacerbation of brain damage after brain ischemia. Because of broad substrate selectivity, system L transporters such as LAT1 transport amino acid-related compounds including L-Dopa and function as a drug transporter. System L also interacts with some environmental toxins with amino acid-related structure such as cysteine-conjugated methylmercury. Therefore, these transporter would be candidates for drug targets based on new therapeutic strategies.
최대우,김도경,Yoshikatsu Kanai,Michael F. Wempe,Hitoshi Endou,김종근 대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.6
Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and presumed to support their increased growth and proliferation. This study examined the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its mechanism for cell death in Saos2 human osteosarcoma cells. FOB human osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2 cells was especially weak. JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, potently inhibited L-leucine uptake in Saos2 cells. As expected, the intrinsic ability of JPH203 to inhibit L-leucine uptake was far more efficient than that of BCH in Saos2 cells. Likewise, JPH203 and BCH inhibited Saos2 cell growth with JPH203 being superior to BCH in this regard. Furthermore, JPH203 increased apoptosis rates and formed DNA ladder in Saos2 cells. Moreover, JPH203 activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. These results suggest that the inhibition of LAT1 activity via JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by inducing the intracellular depletion of neutral amino acids essential for cell growth in Saos2 human osteosarcoma cells.
Matrices for the Analysis of Glycosphingolipids by LC-MS
Akemi Suzuki,Hideshi Fujiwaki,Yoshikatsu Umemura 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1
Recent advances in mass spectrometry make our view of glycosphingolipids (GSLs) com- pletely different from the previous one. LC-MS is applicable to GSL mixture in a smallamount, and provides structural information of carbohydrate chains and ceramides andpossibly quantitative results. However, several subjects remain to be carefully clarified.Critical subjects are matrices used for enhancing ionization of GSLs and the prepara- tion of standard or isotope-labeled GSLs for quantitation. We have tested several matrices for neutral GSLs and acidic GSLs (gangliosides) in the analysis of negative ion mode. Negative ion mode provides more fragment ions derived from carbohydrate chains and ceramides. Matrices used for LC analysis with a C30 reversed phase column of neutral GSLs, such as ammonium formate, formic acid, ammonium acetate, and acetic acid, give adduct ions and the ratios of molecularions [M - H]- and adduct ions are different among molecular species of GlcCer as the simplest neutral GSL. Ammonium bicarbonate containing solvents give lesser amount of adducts and can be used for comparing changes of molecular species of neutral GSLs produced by the different conditions of cultured cells or comparing neutral GSLs of different subsets of cells isolated from living organisms. In the analysis of gangliosides, we detected GM1(NeuAc) as a single charged ion [M – H]-,and GM1(NeuGc) as a double charged ion [M - 2H]-2. Other ganglisoides such as GD1, GT1, and GQ1 molecules were detected as double charged ions, therefore, GM1(NeuAc) gives the highest m/z values among these gangliosides, thus detection effi- ciency becomes very low. We have successfully applied LC-MS analysis to gangliosides of mouse thymocytes and CD4+ and CD8+ T cells (Nagafuku et al. 2012). Fortunately, these gangliosides contain N-glycolylneuraminic acid and give double charged ions, even in the case of GM1. When they are activated, the down regulation of CMP- NeuAc hydroxylase which is the rate liming step for the expression of NeuGc containing ganglisodies (Naito et al. 2007), is possibly triggered. Then, the sensitive detection of GM1(NeuAc) must be assured. This is also required for the analysis of microdomains of neuronal cell mem-brane of neural degenerative diseases such as Alzheimer disease and Parkinson disease.