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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.
Molecular Aspects of Organic Ion Transporters in the Kidney
Seok Ho Cha,Hitoshi Endou 대한생리학회-대한약리학회 2001 The Korean Journal of Physiology & Pharmacology Vol.5 No.2
<P> A function of the kidney is elimination of a variety of xenobiotics ingested and wasted endogenous compounds from the body. Organic anion and cation transport systems play important roles to protect the body from harmful substances. The renal proximal tubule is the primary site of carrier-mediated transport from blood into urine. During the last decade, molecular cloning has identified several families of multispecific organic anion and cation transporters, such as organic anion transporter (OAT), organic cation transporter (OCT), and organic anion-transporting polypeptide (oatp). Additional findings also suggested ATP-dependent organic ion transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein (MRP) as efflux pump. The substrate specificity of these transporters is multispecific. These transporters also play an important role as drug transporters. Studies on their functional properties and localization provide information in renal handling of drugs. This review summarizes the latest knowledge on molecular properties and pharmacological significance of renal organic ion transporters.
Oxidative Stress and Chronic Allograft Nephrothy
하헌주,박재현,김유선,Hitoshi Endou 연세대학교의과대학 2004 Yonsei medical journal Vol.45 No.6
Oxidative stress defined as outbalanced generation of reactive oxygen species (ROS) than the existing antioxidative defense mechanisms plays an important role in tissue injury. Ischemia/reperfusion accompanied during organ transplantation is well- established oxidative stress-induced tissue injury. We hypothesized that oxidative stress may also play a role in the development and progression of chronic allograft nephropathy (CAN), since that ROS are major signaling molecules of growth factors and cytokines [platelet-derived growth factors, transforming growth factor-β1 (TGF-β1)] upregulated in the kidney of CAN, that ROS in turn upregulate TGF-β1, and that mycophenolic acid may inhibit features of CAN [proliferation and extracellular matrix (ECM) accumulation in vascular smooth muscle cells and glomerular mesangial cells] through inhibiting cellular ROS. Cellular ROS activate signal transduction cascade (protein kinase C, mitogen-activated protein kinases, and janus kinases) and transcription factors (nuclear factor-κB, activated protein-1, specificity protein 1, and signal transducers and activators of transcription) leading to regulation of genes and proteins involved in cellular proliferation, ECM remodeling, and apoptosis accompanied in CAN. This review is intended to provide an overview of oxidative stress in renal allograft nephropathy.
Chairoungdua, Arthit,Iribe, Yuji,Kanai, Yoshikatsu,Endou, Hitoshi,Aisaki, Ken-ichi,Larashi, Katsuhide,Kanno, Jun,Baniasadi, Shadi 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.4
Inhibition of LAT1 (L-type amino acid transporter 1 ) activity in tumor cells could be effective in the inhibition of tumor cell growth by depriving tumor cells of essential amino acids. Because of the high level of expression of LAT1 in tumor cells, LAT1 inhibitors would be useful for anticancer therapy in suppressing tumor growth without affecting normal tissues. In recent years, cDNA microarray technique is useful technology for anticancer drug development. It allows identifying and characterizing new targets for developments in cancer drug therapy through the understanding genes involved in drug action. The present study was designed to investigate gene expression profile induced by LAT1 inhibitor using gene chip technology. Human bladder carcinoma cells (T24 cells) were treated with classical system L inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). Gene chip experiment was applied for treated and untreated cells after 3 and f2 h. Two independent experiments with a high degree of concordance identified the altered expression of 151 and 200 genes after 3 and 12 h BCH treatment. Among these genes, 132 and 13 were up-regulated and 19 and 187 were down-regulated by 3 and 12 h BCH treatment respectively. We found that BCH affected the expression of a large number of genes that are related to the control of cell survival and physiologic behaviors. These data are useful for understanding of intracellular signaling of cell growth inhibition induced by LAT1 inhibitors as candidate for anticancer drug therapy.
Improving the Electrical Conductivity of PEDOT:PSS Films by Binary Secondary Doping
Zhengyou Zhu,Congcong Liu,Jingkun Xu,Qinglin Jiang,Hui Shi,Endou Liu 대한금속·재료학회 2016 ELECTRONIC MATERIALS LETTERS Vol.12 No.1
In this work, the electrical conductivity of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) films was effectively enhanced by binarysecondary doping. Initially, doping with 5 vol.% dimethyl sulfoxide (DMSO)improved the electrical conductivity from 0.3 S cm−1 to 437 S cm−1 and a furtherincrease to 950 S cm−1 was achieved by adding LiClO4. The conductivity value wereport here is one of the highest reported for pretreated PEDOT:PSS films. Theobtained maximum electrical conductivity is almost 3000 times higher than thatshown by pristine PEDOT:PSS films. The increase in the electrical conductivity isascribed to the synergistic effect of the two dopants. Fourier transform infraredspectra indicated the absence of any changes to the chemical structure ofPEDOT:PSS. Atomic force microscopy images demonstrate an increased surfaceroughness and suggest the occurrence of conformational changes of PEDOT chainsfrom the coiled to coil-extended one, which is the key reason for the electricalconductivity enhancement. The pretreatments we propose here are rapid, simple andeffective for the large-scale preparation of high-conductivity PEDOT:PSS films.