Hideyo Sato

Yamagata University, Ямагата, Yamagata, Japan

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Publications (27)91.15 Total impact

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    ABSTRACT: In mammalian cultured cells, the activity of a cystine/glutamate transporter, designated System x(c)(-), has been shown to be essential for maintaining intracellular glutathione levels and the extracellular cystine/cysteine redox balance. The substrate-specific subunit of this transporter, xCT, is strongly induced by various stimuli, including oxidative stress, which suggests that xCT is one of the adaptive cellular defense systems against these types of stress. Embryonic fibroblasts from xCT-deficient mice fail to survive unless a cysteine precursor, N-acetylcysteine, is present. However, it is unclear whether xCT has similar functions in vivo because xCT-deficient mice are apparently normal. In this study, we investigated the phenotypes of the xCT-deficient mice under paraquat-induced oxidative stress. At a paraquat dose of 45mg/kg, the survival rate of the xCT-deficient mice was significantly lower than that of the wild-type mice. Under this condition, total glutathione [the reduced form of glutathione (GSH)+the oxidized form of GSH (GSSG)] levels in the lungs of the xCT-deficient mice were lower than those in the lungs of the wild-type mice. Histopathological examinations showed that paraquat administration worsened the alveolar structures of the xCT-deficient mice compared with the wild-type mice. After paraquat treatment, obvious 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2- nonenal reactivities were detected in the lung of the xCT-deficient mice. Although xCT expression was slightly detectable in the lungs of the normal wild-type mice, paraquat administration induced xCT mRNA expression in the lung. Constitutive expression of xCT mRNA was detected in alveolar macrophages isolated from the pulmonary lavage fluid of the wild-type mice, and paraquat administration strongly enhanced xCT mRNA expression in these cells. GSH levels in bronchoalveolar lavage fluid were significantly higher in the paraquat-treated wild-type mice than in the paraquat-treated xCT-deficient mice. These results suggest that xCT contributes to the maintenance of glutathione levels in lungs and the glutathione redox state as a protective system against paraquat toxicity in vivo.
    Free Radical Biology and Medicine 10/2012; · 5.27 Impact Factor
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    ABSTRACT: The anti-diabetic effects of a kaempferol glycoside-rich fraction (KG) prepared from leaves of unripe Jindai soybean (Edamame) and kaempferol, an aglycone of kaempferol glycoside, were determined in genetically type 2 diabetic KK-A(y) mice. The hemoglobin A(₁c) level was decreased and tended to be decreased by respectively feeding KG and kaempferol (K). The area under the curve (AUC) in the oral glucose tolerance test (OGTT) tended to be decreased by feeding K and KG. The liver triglyceride level and fatty acid synthase activity were both decreased in the mice fed with KG and K when compared to those parameters in the control mice. These results suggest that KG and K would be useful to improve the diabetes condition. The major flavonoids in KG were identified as kaempferol 3-O-β-D-glucopyranosyl(1→2)-O-[α-L-rhamnopyranosyl(1→6)]-β-D-galactopyranoside, kaempferol 3-O-β-D-glucopyranosyl(1→2)-O-[α-L-rhamnopyranosyl(1→6)]-β-D-glucopyranoside, kaempferol 3-O-β-D-(2-O-β-D-glucopyranosyl) galactopyranoside and kaempferol 3-O-β-D-(2,6-di-O-α-L-rhamnopyranosyl) galactopyronoside, suggesting that these compounds or some of them may be concerned with mitigation of diabetes.
    Bioscience Biotechnology and Biochemistry 09/2011; 75(9):1677-84. · 1.27 Impact Factor
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    ABSTRACT: System x(c)- exchanges intracellular glutamate for extracellular cystine, giving it a potential role in intracellular glutathione synthesis and nonvesicular glutamate release. We report that mice lacking the specific xCT subunit of system x(c)- (xCT(-/-)) do not have a lower hippocampal glutathione content, increased oxidative stress or brain atrophy, nor exacerbated spatial reference memory deficits with aging. Together these results indicate that loss of system x(c)- does not induce oxidative stress in vivo. Young xCT(-/-) mice did however display a spatial working memory deficit. Interestingly, we observed significantly lower extracellular hippocampal glutamate concentrations in xCT(-/-) mice compared to wild-type littermates. Moreover, intrahippocampal perfusion with system x(c)- inhibitors lowered extracellular glutamate, whereas the system x(c)- activator N-acetylcysteine elevated extracellular glutamate in the rat hippocampus. This indicates that system x(c)- may be an interesting target for pathologies associated with excessive extracellular glutamate release in the hippocampus. Correspondingly, xCT deletion in mice elevated the threshold for limbic seizures and abolished the proconvulsive effects of N-acetylcysteine. These novel findings sustain that system x(c)-) is an important source of extracellular glutamate in the hippocampus. System x(c)(-) is required for optimal spatial working memory, but its inactivation is clearly beneficial to decrease susceptibility for limbic epileptic seizures.
    Journal of Neuroscience 04/2011; 31(15):5792-803. · 6.91 Impact Factor
  • Marcus Conrad, Hideyo Sato
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    ABSTRACT: The oxidative stress-inducible cystine/glutamate exchange system, system x (c) (-) , transports one molecule of cystine, the oxidized form of cysteine, into cells and thereby releases one molecule of glutamate into the extracellular space. It consists of two protein components, the 4F2 heavy chain, necessary for membrane location of the heterodimer, and the xCT protein, responsible for transport activity. Previously, system x (c) (-) has been regarded to be a mere supplier of cysteine to cells for the synthesis of proteins and the antioxidant glutathione (GSH). In that sense, oxygen, electrophilic agents, and bacterial lipopolysaccharide trigger xCT expression to accommodate with increased oxidative stress by stimulating GSH biosynthesis. However, emerging evidence established that system x (c) (-) may act on its own as a GSH-independent redox system by sustaining a redox cycle over the plasma membrane. Hallmarks of this cycle are cystine uptake, intracellular reduction to cysteine and secretion of the surplus of cysteine into the extracellular space. Consequently, increased levels of extracellular cysteine provide a reducing microenvironment required for proper cell signaling and communication, e.g. as already shown for the mechanism of T cell activation. By contrast, the enhanced release of glutamate in exchange with cystine may trigger neurodegeneration due to glutamate-induced cytotoxic processes. This review aims to provide a comprehensive picture from the early days of system x (c) (-) research up to now.
    Amino Acids 03/2011; 42(1):231-46. · 3.91 Impact Factor
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    ABSTRACT: Malfunctioning of system x(c)(-), responsible for exchanging intracellular glutamate for extracellular cystine, can cause oxidative stress and excitotoxicity, both important phenomena in the pathogenesis of Parkinson's disease (PD). We used mice lacking xCT (xCT(-/-) mice), the specific subunit of system x(c)(-), to investigate the involvement of this antiporter in PD. Although cystine that is imported via system x(c)(-) is reduced to cysteine, the rate-limiting substrate in the synthesis of glutathione, deletion of xCT did not result in decreased glutathione levels in striatum. Accordingly, no signs of increased oxidative stress could be observed in striatum or substantia nigra of xCT(-/-) mice. In sharp contrast to expectations, xCT(-/-) mice were less susceptible to 6-hydroxydopamine (6-OHDA)-induced neurodegeneration in the substantia nigra pars compacta compared to their age-matched wild-type littermates. This reduced sensitivity to a PD-inducing toxin might be related to the decrease of 70% in striatal extracellular glutamate levels that was observed in mice lacking xCT. The current data point toward system x(c)(-) as a possible target for the development of new pharmacotherapies for the treatment of PD and emphasize the need to continue the search for specific ligands for system x(c)(-).
    The FASEB Journal 12/2010; 25(4):1359-69. · 5.70 Impact Factor
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    ABSTRACT: GSH is the major antioxidant and detoxifier of xenobiotics in mammalian cells. A strong decrease of intracellular GSH has been frequently linked to pathological conditions like ischemia/reperfusion injury and degenerative diseases including diabetes, atherosclerosis, and neurodegeneration. Although GSH is essential for survival, the deleterious effects of GSH deficiency can often be compensated by thiol-containing antioxidants. Using three genetically defined cellular systems, we show here that forced expression of xCT, the substrate-specific subunit of the cystine/glutamate antiporter, in gamma-glutamylcysteine synthetase knock-out cells rescues GSH deficiency by increasing cellular cystine uptake, leading to augmented intracellular and surprisingly high extracellular cysteine levels. Moreover, we provide evidence that under GSH deprivation, the cytosolic thioredoxin/thioredoxin reductase system plays an essential role for the cells to deal with the excess amount of intracellular cystine. Our studies provide first evidence that GSH deficiency can be rescued by an intrinsic genetic mechanism to be considered when designing therapeutic rationales targeting specific redox enzymes to combat diseases linked to GSH deprivation.
    Journal of Biological Chemistry 05/2010; 285(29):22244-53. · 4.65 Impact Factor
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    ABSTRACT: This study examined the question of whether deficiency of xCT, a cystine-transporter gene, exacerbates ischemia-reperfusion-induced acute renal failure (ARF). Two weeks after the right nephrectomy of male mice at 16-18weeks of age, the left renal vessels were clamped for 45min to induce renal ischemia. After (24h) induction of ischemia, xCT(-/-) mice had elevated concentrations of blood urea nitrogen and creatinine indicative of ARF, while in xCT(+/-) and xCT(+/+) mice, these parameters did not differ from the sham-operated mice. Immunohistochemical analyses of kidneys using antibodies against the oxidative stress markers revealed stronger staining in xCT(-/-) mice compared with xCT(+/+) mice. Induction of xCT mRNA in the kidneys of xCT(+/+) mice was demonstrated using reverse transcriptase (RT)-PCR analysis and was further confirmed using quantitative RT-PCR. These data provide the first in vivo evidence that xCT is induced by oxidative stress and helps prevent ischemia-reperfusion injury to kidneys.
    Archives of Biochemistry and Biophysics 09/2009; 490(1):63-9. · 3.37 Impact Factor
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    ABSTRACT: The anti-inflammatory properties of transforming growth factor-beta(1) (TGF-beta(1)) account for its protection against atherosclerotic plaque rupture. This study investigates whether activation of the Nrf2 (nuclear factor erythroid 2 [NF-E2]-related factor 2) transcription pathway is involved in TGF-beta(1) mediated induction of the antioxidant enzyme heme oxygenase-1 (HO-1) in smooth muscle cells (SMC). Human aortic smooth muscle cells (HAoSMC) or wild-type and Nrf2-deficient mouse (MAoSMC) aortic SMC were treated with TGF-beta(1) (2.5-10 ng/ml, 0-24 hrs). We report the first evidence that TGF-beta(1) induces Nrf2 mediated HO-1 expression and antioxidant response element activity, which was paralleled by enhanced superoxide production and expression of the NAD(P)H oxidase subunit p22(phox). TGF-beta(1) failed to induce HO-1 expression in MAoSMC derived from Nrf2-deficient mice, and HO-1 induction by TGF-beta(1) in HAoSMC was attenuated by inhibition of extracellular signal regulated kinase or c-jun-N-terminal kinase but not p38 mitogen activated protein kinase. Inhibition of NAD(P)H oxidase or scavenging of superoxide diminished HO-1 induction in response to TGF-beta(1). The oxidative stress agents glucose oxidase (GOx) and diethylmaleate enhanced TGF-beta(1) generation and HO-1 expression in HAoSMC, while antagonism of TGF-beta(1) signalling by adenoviral Smad7 overexpression attenuated their induction of HO-1. Pre-treatment of HAoSMC with TGF-beta(1) reduced nuclear translocation of the pro-apoptotic mediator p53 elicited by GOx. Our findings demonstrate that Nrf2 is a new target of TGF-beta(1) signalling in the vasculature which may contribute to the atheroprotective properties attributed to this growth factor.
    Journal of Cellular and Molecular Medicine 09/2009; 13(8B):2282-92. · 4.75 Impact Factor
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    ABSTRACT: The effects of a pumpkin paste concentrate and its components on oral glucose tolerance and serum lipid levels were determined in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. In the oral glucose tolerance test, the pumpkin paste concentrate-fed group maintained a lower glucose level than the control group between 15 and 60 min. The compounds considered to be effective in improving glucose tolerance and contained in the methanol extract of the pumpkin in relatively abundant amounts were isolated and identified as trigonelline (TRG) and nicotinic acid (NA).Feeding a diet containing TRG and NA respectively improved and tended to improve glucose tolerance. The insulin level increased after 15 min in the TRG-fed GK rats and then gradually decreased over the next 120 min. In contrast, a gradual increase was seen in the insulin level over 120 min in the control GK rats not fed with TRG, suggesting that TRG could improve the insulin resistance. The serum and liver triglyceride (TG) levels in the TRG- and NA-fed GK rats were lower than those in the control GK rats. Lower activity of liver fatty acid synthase (FAS), and higher activity of liver carnitine palmitoyl transferase (CPT) and glucokinase (GLK) in the TRG- and NA-fed GK rats than in the control GK rats were observed. This suggests that the regulation of these enzyme activities by TRG and NA was closely related to the suppression of both TG accumulation and the progression of diabetes.
    Bioscience Biotechnology and Biochemistry 06/2009; 73(5):1033-41. · 1.27 Impact Factor
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    ABSTRACT: The anti-inflammatory properties of transforming growth factorbeta-1 (TGFbeta-1) account for its protection against atherosclerotic plaque rupture. This study investigates whether activation of the Nrf2 transcription pathway is involved in TGFbeta-1 mediated induction of the antioxidant enzyme heme oxygenase-1 (HO-1) in smooth muscle cells (SMC). Human (HAoSMC) or wild-type and Nrf2 deficient mouse (MAoSMC) aortic SMC were treated with TGFbeta-1 (2.5-10 ng/ml, 0-24 h). We report the first evidence that TGFbeta-1 induces Nrf2 mediated HO-1 expression and antioxidant response element activity, which was paralleled by enhanced superoxide production and expression of the NAD(P)H oxidase subunit p22(phox). TGFbeta-1 failed to induce HO-1 expression in MAoSMC derived from Nrf2 deficient mice, and HO-1 induction by TGFbeta-1 in HAoSMC was attenuated by inhibition of extracellular signal regulated kinase or c-jun-N-terminal kinase but not p38 mitogen activated protein kinase. Inhibition of NAD(P)H oxidase or scavenging of superoxide diminished HO-1 induction in response to TGFbeta-1. The oxidative stress agents glucose oxidase and diethylmaleate enhanced TGFbeta-1 generation and HO-1 expression in HAoSMC, while antagonism of TGF(-1 signalling by adenoviral Smad7 overexpression attenuated their induction of HO-1. Pretreatment of HAoSMC with TGF(-1 reduced nuclear translocation of the pro-apoptotic mediator p53 elicited by glucose oxidase. Our findings demonstrate that Nrf2 is a new target of TGFbeta-1 signalling in the vasculature which may contribute to the atheroprotective properties attributed to this growth factor.
    Journal of Cellular and Molecular Medicine 01/2009; · 4.75 Impact Factor
  • Bioscience Biotechnology and Biochemistry - BIOSCI BIOTECHNOL BIOCHEM. 01/2009; 73(5):1033-1041.
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    ABSTRACT: Altered glutamate signaling is associated with Parkinson's disease. To study the involvement of the cystine/glutamate antiporter in the pathogenesis of Parkinson's disease, we developed new polyclonal antibodies recognizing xCT, the specific subunit of this antiporter. The striatal xCT protein expression level was investigated in a hemi-Parkinson rat model, using semiquantitative western blotting. We observed time-dependent changes after a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway with increased expression levels in the deafferented striatum after 3 weeks. Twelve weeks postlesion, expression levels returned to normal. These data suggest, for the first time, an involvement of the cystine/glutamate antiporter in determining the aberrant glutamate neurotransmission in the striatum of a parkinsonian brain.
    Neuroreport 10/2008; 19(16):1589-92. · 1.40 Impact Factor
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    ABSTRACT: Because glutathione scavenges reactive oxygen species (ROS) and also donates electrons to antioxidative systems, it may compensate for the oxidative stress caused by SOD1 deficiency. The cystine/glutamate transporter, which consists of two proteins, xCT and 4F2hc, has been designated system x (c) (-) . This transporter system plays a role in the maintenance of glutathione levels in mammalian cells. In the present study, we created SOD1 (-/-); xCT (-/-) double-knockout mice by intercrossing xCT-knockout and SOD1-knockout animals. We determined if the double-knockout mice express the phenotypic characteristics unique to SOD1 (-/-) mice-increased oxidative stress and the production of autoantibodies against erythrocytes. We also compared the phenotype of the double-knockout mice with those of the single-knockout and wild-type mice. Although two major antioxidative systems were found to be defective in the SOD1 (-/-); xCT (-/-) mice, relative to the SOD1 (-/-) mice, no functional deficits were observed. Based on these results, it appears that defects in system x (c) (-) do not exacerbate the phenotypic consequences of SOD1 deficiency in postnatal mice under ordinary breeding conditions.
    Molecular and Cellular Biochemistry 08/2008; 319(1-2):125-32. · 2.33 Impact Factor
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    ABSTRACT: Isorhamnetin 3-O-glucoside, which was contained together with isorhamnetin 3,7-di-O-glucoside in atsumi-kabu leaves, suppressed increases in the plasma ALT and AST activities of mice with liver injury induced by the injection of carbon tetrachloride, but no suppression by isorhamnetin 3,7-di-O-glucoside was apparent. This result indicates that the release of glucose at the 7-position in isorhamnetin 3,7-di-O-glucoside was very important to mitigating liver injury.
    Bioscience Biotechnology and Biochemistry 04/2008; 72(3):856-60. · 1.27 Impact Factor
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    ABSTRACT: Reactive oxygen species (ROS) produced by neutrophils are essential in the host defense against infections but may be harmful to neutrophils themselves. Glutathione (GSH) plays a pivotal role in protecting cells against ROS-mediated oxidant injury. Cystine/glutamate transporter, designated as system xc- and consisting of two proteins, xCT and 4F2hc, is important to maintain GSH levels in mammalian-cultured cells. In the present paper, we have investigated system xc- in neutrophils. In human peripheral blood neutrophils, neither the activity of system xc- nor xCT mRNA was detected. The activity was induced, and xCT mRNA was expressed when they were cultured in vitro. The mRNA expression was much enhanced in the presence of opsonized zymosan or PMA. In contrast, mouse peritoneal exudate neutrophils, immediately after preparation, exhibited system xc- activity and expressed xCT mRNA. The activity and the expression were heightened further when they were cultured. Peritoneal exudate cells (mostly neutrophils) from xCT-deficient (xCT-/-) mice had lower cysteine content than those from the wild-type mice. GSH levels in the xCT-/-cells decreased rapidly when they were cultured, whereas those in the wild-type cells were maintained during the culture. Apoptosis induced in culture was enhanced in the xCT-/-cells compared with the wild-type cells. These results suggest that system xc- plays an important role in neutrophils when they are activated, and their GSH consumption is accelerated.
    Journal of Leukocyte Biology 05/2007; 81(4):974-82. · 4.57 Impact Factor
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    ABSTRACT: Brain cell suspensions obtained from cerebrum of fetal rats were cultured and after 5 days neurons were separated from the residual cells. These purified neurons, which were replated on the dish, started to die within 24 h in culture. Glutathione content of these neurons decreased rapidly to less than one-tenth of the initial level after 24 h. In the presence of alpha-tocopherol, a well-known antioxidant, the neurons survived for at least 3 days, though glutathione content remained very low. Butylated hydroxyanisol had similar effect, but ascorbic acid and uric acid had no or very little effect. Serotonin, which is assumed to have an antioxidant activity, kept the neurons alive for 3 days. These results suggest that neurons separated from the other types of cells cannot survive due to the oxidative stress, which may otherwise be neutralized by a mechanism involving glutathione, and that antioxidants including serotonin has a beneficial effect on these purified neurons.
    Brain Research 03/2007; 1131(1):11-6. · 2.88 Impact Factor
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    ABSTRACT: Cystine/glutamate transporter, system xc-, contributes to the maintenance of intracellular glutathione levels and the redox balance in the extracellular space. The main component of the transporter, xCT, is known to be strongly induced by various stimuli like oxidative stress in mammalian cultured cells. We examined the expression of xCT mRNA in vivo in the experimental endotoxemia. Northern blot analysis and in situ hybridization were used to investigate the expression of xCT mRNA in the tissues of the mice exposed to bacterial lipopolysaccharide (LPS). Northern blot analysis revealed that xCT mRNA was constitutively expressed in the brain, thymus, and spleen, and that the expression of xCT mRNA was strongly up-regulated in thymus and spleen by the administration of a sublethal dose of LPS. In addition to brain, thymus, and spleen, xCT mRNA was detected also in the bronchiolar epithelium of the lung by the administration of the lethal dose of LPS. xCT is induced in some specific tissues by the administration of LPS. The results suggest that cystine/glutamate transporter plays an important role under the inflammatory conditions.
    Journal of Inflammation 02/2007; 4:20. · 2.55 Impact Factor
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    ABSTRACT: Cystine/glutamate transporter, designated as system x(-)(c), mediates cystine entry in exchange for intracellular glutamate in mammalian cells. This transporter consists of two protein components, xCT and 4F2 heavy chain, and the former is predicted to mediate the transport activity. This transporter plays a pivotal role for maintaining the intracellular GSH levels and extracellular cystine/cysteine redox balance in cultured cells. To clarify the physiological roles of this transporter in vivo, we generated and characterized mice lacking xCT. The xCT(-/-) mice were healthy in appearance and fertile. However, cystine concentration in plasma was significantly higher in these mice, compared with that in the littermate xCT(-/-) mice, while there was no significant difference in plasma cysteine concentration. Plasma GSH level in xCT(-/-) mice was lower than that in the xCT(-/-) mice. The embryonic fibroblasts derived from xCT(-/-) mice failed to survive in routine culture medium, and 2-mercaptoethanol was required for survival and growth. When 2-mercaptoethanol was removed from the culture medium, cysteine and GSH in these cells dramatically decreased, and cells started to die within 24 h. N-Acetyl cysteine also rescued xCT(-/-)-derived cells and permitted growth. These results demonstrate that system x(-)(c) contributes to maintaining the plasma redox balance in vivo but is dispensable in mammalian development, although it is vitally important to cells in vitro.
    Journal of Biological Chemistry 12/2005; 280(45):37423-9. · 4.65 Impact Factor
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    ABSTRACT: Recent studies have demonstrated that depletion of amino acids results in the induction of several genes and that a genomic cis-element termed amino acid response element (AARE) is required for the induction. System x(c)(-) is an anionic amino acid transport system highly specific for cystine and glutamate, and its activity is known to be induced by cystine deprivation. This transporter is composed of two protein components, xCT and 4F2 heavy chain, and xCT is thought to mediate the transport activity. In the present study, the molecular mechanism for the induction of xCT by amino acid deprivation has been investigated. In mouse NIH3T3 cells, the activity of system x(c)(-) and xCT mRNA is induced not only by deprivation of cystine but also by deprivation of other amino acids. Two AAREs, each located in the opposite direction with an intervening sequence, were found in the 5'-flanking region of the mouse xCT gene. Promoter analysis revealed that both AAREs were necessary for the maximal induction of xCT mRNA in response to the amino acid deprivation. Glucose deprivation had no effect on the induction of the activity of system x(c)(-). Electrophoretic mobility shift assay showed that ATF4, but not ATF2, is involved in the amino acid control of xCT expression. These results demonstrate that xCT is a new member of the proteins whose transcriptional control by the amino acid deprivation is mediated by AARE.
    Biochemical and Biophysical Research Communications 01/2005; 325(1):109-16. · 2.28 Impact Factor
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    ABSTRACT: The expression of the activity of cystine/glutamate exchange transporter, designated system x(c)(-), requires two components, xCT and 4F2 heavy chain (4F2hc) in Xenopus oocytes. rBAT (related to b(0,+) amino acid transporter) has a significant homology to 4F2hc and is known to be located in the apical membrane of epithelial cells. To determine whether xCT can associate with rBAT and express the activity of system x(c)(-), xCT, and rBAT were co-expressed in Xenopus oocytes and in mammalian cultured cells. In the oocytes injected with rBAT cRNA alone, the activities of cystine and arginine transport were induced, indicating that the system b(0,+)-like transporter was expressed by associating the exogenous rBAT with an endogenous b(0,+)AT-like factor as reported previously. In the oocytes injected with xCT and rBAT cRNAs, the activity of cystine transport was further induced. This induced activity of cystine transport was partially inhibited by glutamate or arginine and completely inhibited by adding both amino acids. In these oocytes, the activity of glutamate transport was also induced and it was strongly inhibited by cystine. In NIH3T3 cells transfected with xCT cDNA alone, the activity of cystine transport was significantly increased, and in the cells transfected with both xCT and rBAT cDNAs, the activity of cystine transport was further enhanced. The enhanced activity was Na(+)-independent and was inhibited by glutamate and homocysteate. These results indicate that rBAT can replace 4F2hc in the expression of the activity of system x(c)(-) and suggest that system x(c)(-) activity could be expressed in the apical membrane of epithelial cells.
    Biochemical and Biophysical Research Communications 07/2003; 305(3):611-8. · 2.28 Impact Factor

Publication Stats

658 Citations
91.15 Total Impact Points

Institutions

  • 2007–2012
    • Yamagata University
      • • Department of Biochemistry and Molecular Biology
      • • Department of Bioresource Engineering
      Ямагата, Yamagata, Japan
  • 2011
    • Helmholtz Zentrum München
      • Institut für Klinische Molekularbiologie und Tumorgenetik
      München, Bavaria, Germany
  • 2009
    • Iwate University
      Morioka, Iwate, Japan
  • 1991–2007
    • University of Tsukuba
      • Institute of Basic Medical Sciences
      Tsukuba, Ibaraki-ken, Japan
  • 2003
    • University of London
      Londinium, England, United Kingdom
  • 1995–1997
    • King's College London
      • School of Biomedical Sciences
      Londinium, England, United Kingdom