• The Korean Journal of Physiology and Pharmacology
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• v.8 no.3
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• pp.117-127
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• 2004

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.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.498-505
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• 2021

Amyotrophic lateral sclerosis (ALS) is a lethal neurological disorder characterized by the deterioration of motor neurons. The aim of this study was to investigate alteration of cationic amino acid transporter (CAT-1) activity in the transport of lysine and the pretreatment effect of lysine on pro-inflammatory states in an amyotrophic lateral sclerosis cell line. The mRNA expression of cationic amino acid transporter 1 was lower in NSC-34/hSOD1^G93A (MT) than the control cell line (WT), lysine transport is mediated by CAT-1 in NSC-34 cell lines. The uptake of [³H]L-lysine was Na⁺-independent, voltage-sensitive, and strongly inhibited by inhibitors and substrates of cationic amino acid transporter 1 (system y⁺). The transport process involved two saturable processes in both cell lines. In the MT cell line, at a high-affinity site, the affinity was 9.4-fold higher and capacity 24-fold lower than that in the WT; at a low-affinity site, the capacity was 2.3-fold lower than that in the WT cell line. Donepezil and verapamil competitively inhibited [³H]L-lysine uptake in the NSC-34 cell lines. Pretreatment with pro-inflammatory cytokines decreased the uptake of [³H]L-lysine and mRNA expression levels in both cell lines; however, the addition of L-lysine restored the transport activity in the MT cell lines. L-Lysine exhibited neuroprotective effects against pro-inflammatory states in the ALS disease model cell lines. In conclusion, studying the alteration in the expression of transporters and characteristics of lysine transport in ALS can lead to the development of new therapies for neurodegenerative diseases.

• Proceedings of the SCSK Conference
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• 2003.09b
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• pp.145-148
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• 2003

Previously, we reported that L-PCA enhanced blood circulation by modulating constitutive NO production. It was that L-PCA increased L-Arg uptake into endothelial cell, followed by the enhancement of NO production. Then we recommended the use of L-PCA for cosmetics, not only as humectants but also as enhancer of blood circulation. Since L-Arg is transported into endothelial cells by CAT (cationic amino acid transporter), it is expected that L-PCA also increase the uptake of basic amino acid, L-Lys. In this study, the uptakes of some amino acids into cells were evaluated by using 3H-labelled amino acid. Then we found the tendency that the uptake of L-Lys into endothelial cells was also enhanced by L-PCA. And the evident effect was observed in the epidermal fibroblasts, which had also CAT. Furthermore, it was found that the transportation of the other type of amino acids were not enhanced by L-PCA. That is to say, a famous moisturizer, L-PCA, has some effects on basic amino acid transport into cells.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.5
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• pp.712-720
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• 2009

The goal of this study was to elucidate the expression and segmental distribution of the glomerular cationic amino acid metabolism transporter-2 (CAT-2) and thus to improve our understanding of porcine cationic amino acid transporters and amino acid absorption. Porcine CAT-2 was cloned, sequenced and characterized. The predicted amino acid sequence of porcine CAT-2 shared 86.1% and 92.1% identity with human and mouse CAT-2A, respectively. The tissue distribution patterns and ontogenic changes of CAT-2 mRNAs were determined by real-time Q-PCR. The results showed that porcine CAT-2 was highly expressed in the heart and intestinal tract (duodenum, ileum and jejunum). In addition, the mRNA of CAT-2 was found in liver, lung, kidney, brain and muscle. Within the intestinal tract, CAT-2 mRNA was most abundant in the ileum and rarely expressed in the duodenum. In the duodenum, the levels of CAT-2 mRNA reached their peak on day 7 (p<0.05) while in the jejunum, levels were low on day 1 and 7 and increased rapidly after day 26 before peaking on days 30 and 60 (p<0.05). The levels then dramatically decreased by day 90 (p<0.05). In the ileum, levels achieved their maximum on day 30 and then decreased significantly on day 60 (p<0.05).

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.5
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• pp.710-719
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• 2001

Several amino acid transport systems in mammary gland have been characterized during the last few years. These systems may be divided into two broad categories based on whether they are sodium-dependent or $Na^{+}$-independent, and each of these categories is subdivided into 3 groups depending on whether the systems prefer zwitterionic, cationic or anionic substrates. The zwitterion preferring transport processes in mammary gland are $Na^{+}$-dependent system A and $Na^{+}$-independent systems L and T. System $y^{+}$ is a $Na^{+}$-independent transporter of cationic amino acids and $X_{AG^{-}}$ is a $Na^{+}$-dependent system for anionic amino acids. A ($Na^{+}+Cl^{-}$)-dependent system, selective for $\beta$-amino acids has been reported in rat mammary tissue. In addition, there is yet another class of transporters that have still broader specificity. The $Na^{+}$-dependent systems $BCl^{-}$-dependent and $BCl^{-}$-independent and $Na^{+}$-independent system $y^{+}L$ have been reported to mediate the transport of zwitterionic as well as cationic amino acids. Each system has been characterized with respect to its substrate specificity, affinity, kinetics and ion-dependence. Transport of amino acids by mammary tissue is regulated by i) the intracellular substrate concentration, ii) lactogenic hormones and iii) milk stasis. Four of the above transport systems (i.e. A, L, $y^{+}$ and $BCl^{-}$-independent) are up-regulated by lactogenic hormones (insulin, cortisol and prolactin) in mammary gland.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.8
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• pp.1134-1142
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• 2008

Cationic amino acid transporter $b^{0,+}AT$ (HGMW-approved gene symbol SLC7A9, solute carrier family 7, member 9) plays a crucial role in amino acid nutrition. In the present study, we describe the cloning and sequencing of porcine $b^{0,+}AT$. Based on the sequence of porcine $b^{0,+}AT$ deposited in the NCBI (National Center for Biotechnological Information), we identified a putative porcine homologue. Using rapid amplification of cDNA ends (RACE), the full-length cDNA encoding porcine $b^{0,+}AT$ was isolated. The porcine $b^{0,+}AT$ cDNA was 1,680 bp long, encoding a 487 amino acid trans-membrane protein. The predicted amino acid sequence was found to have 88.9% and 87.1% identity with human and mouse $b^{0,+}AT$, respectively. Real-time RT-PCR indicated porcine $b^{0,+}AT$ transcripts expressed in heart, kidney, muscle and small intestine. The small intestine had the highest $b^{0,+}AT$ mRNA abundance while the muscle had the lowest (p<0.05). Along the longitudinal axis, the ileum had the highest $b^{0,+}AT$ mRNA abundance while the colon had the lowest (p<0.05). The $b^{0,+}AT$ mRNA level was highest on day 7 and 90 in the duodenum (p<0.05). It increased from day 1 to day 26 in the jejunum (p>0.05) and had the highest abundance on day 60 (p<0.05). There was, however, no difference between day 1, 7, 26, 30, 90 and 150 (p>0.05). The strongest $b^{0,+}AT$ expression appeared on day 7 in the ileum before weaning, and then decreased till day 30 but rose gradually again from day 60 to 150 (p<0.05).

• The Journal of Natural Sciences
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• v.8 no.2
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• pp.35-41
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• 1996

To find the substrate interacting site of the MCAT1, charged amino acid residues in the transmembrane domain were changed to opposite charged amino acids and studied the arginine uptake, gp70 binding, efflux and protein expression using the Xenopus oocyte expression method. Among the five mutants of MCAT1, the D403K showed the most interesting characteristics, which had normal gp70 binding but low arginine uptake function, that means the normal expression on the membrane but decreased transport function. All mutants except K211E showed decreased arginine efflux, and kinetic study showed decreased Vmax. Together, Clu(403) residue of MCAT1 may show the possible substrate interacting site in the transmembrane domain of MCAT1.

• Journal of Microbiology
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• v.44 no.4
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• pp.447-452
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• 2006

The murine ecotropic retroviral receptor has been demonstrated to function as a mouse cationic amino acid transporter 1(mCAT1), and is comprised of multiple membranespanning domains. Feral mouse (Mus dunni) cells are not susceptible to infection by the ecotropic Moloney murine leukemia virus (MoMLV), although they can be infected by other ecotropic murine leukemia viruses, including Friend MLV and Rauscher MLV. The relative inability of MoMLV to replicate in M. dunni cells has been attributed to two amino acids $(V_{214}\;and\;G_{236})$ located within the third extracellular loop of the M. dunni CAT1 receptor (dCAT1). Via the exchange of the third extracellular loop of the mCAT1 cDNA encoding receptor from the permissive mouse and the corresponding portion of cDNA encoding for the nonpermissive M. dunni receptor, we have identified the most critical amino acid residue, which is a glycine located at position 236 within the third extracellular loop of dCAT1. We also attempted to determine the role of the third extracellular loop of the M. dunni CAT1 receptor with regard to the formation of the syncytium. The relationship between dCAT1 and virus-induced syncytia was suggested initially by our previous identification of two MLV isolates (S82F in Moloney and S84A in Friend MLV), both of which are uniquely cytopathic in M. dunni cells. In an attempt to determine the relationship existing between dCAT1 and the virally-induced syncytia, we infected 293-dCAT1 or chimeric dCAT1 cells with the S82F pseudotype virus. The S82F pseudotype virus did not induce the formation of syncytia, but did show increased susceptibility to 293 cells expressing dCATl. The results of our study indicate that S82F-induced syncytium formation may be the result of cell-cell fusion, but not virus-cell fusion.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.1
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• pp.98-105
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• 2010

A total of 16 crossbred post-weaning pigs (10.64${\pm}$0.27 kg BW) were individually penned and assigned to one of two treatments to investigate the influences of diquat-induced oxidative stress on performance and arginine metabolism. Pigs in the oxidative stress group were injected intra-peritoneally with 10 mg/kg BW of diquat, while the control group were injected with isotonic saline. All pigs were fed ad libitum. The experiment lasted for 7 days. The results indicated that compared with control treatment, oxidative stress induced by diquat significantly decreased average daily gain, intake and feed conversion. The treatment decreased activities of antioxidant enzymes, increased concentration of malondialdehyde in plasma, increased cationic amino acid transporter-1 mRNA level and activity of ornithine aminotransferase and concentrations of arginine and citrulline in the jejunum, decreased the concentrations of arginine in plasma and kidney, and decreased induced nitric oxide synthase mRNA level. It is concluded that oxidative stress induced by diquat can influence absorption and metabolism of arginine and consequently modify the requirement of arginine for post-weaning pigs.