The Experts below are selected from a list of 96 Experts worldwide ranked by ideXlab platform
Toshinori Yamamoto - One of the best experts on this subject based on the ideXlab platform.
-
genetic polymorphism of the human organic Solute Carrier Protein 1 hoscp1 gene in japanese patients with non viral liver carcinoma
Meta Gene, 2014Co-Authors: Mayumi Toda, Yasuna Kobayashi, Noriko Kohyama, Masayuki Ohbayashi, Tomotake Koizumi, Koji Saito, Takeshi Aoki, Masahiko Murakami, Hajime Yasuhara, Toshinori YamamotoAbstract:Human organic Solute Carrier Protein 1 (hOSCP1) is a Na+-independent multispecific organic Solute transporter. To date, several studies have revealed that gene mutations of the transporters are likely to be associated with some diseases; however, there are no data concerning the genetic polymorphism of the hOSCP1 gene in Japanese patients with non-viral liver carcinoma (LC). In the present study, we isolated genomic DNA from a normal portion of LC, and analyzed 41 single nucleotide polymorphisms (SNPs) chosen from a database of SNPs (dbSNPs). We found genotype frequencies for 2 non-synonymous SNPs [rs34409118 (Thr131 → Ala) and rs1416840 (Ile219 → Thr)] and 1 synonymous SNP [rs16822954 (Ser193 → Ser)] to be statistically significant when compared with dbSNPs. No statistical significance was observed in rs2275477 (Gly307 → Arg) in the hOSCP1 gene. With respect to the allele frequency, we also observed rs34409118 to be statistically significant. Interestingly, we found that non-viral LC patients do not carry heterozygous mutations in rs1416840 (A/G) and rs16822954 (A/G), suggesting that a non-Carrier of heterozygous mutations in these two SNPs might be a biomarker for susceptibility for non-viral LC in Japanese. Further analyses of patients with hOSCP1 variants may elucidate the relationship between the hOSCP1 gene and susceptibility of non-viral LC in Japanese patients.
-
rat organic Solute Carrier Protein 1 roscp1 mediated the transport of organic Solutes in xenopus laevis oocytes isolation and pharmacological characterization of roscp1
Life Sciences, 2007Co-Authors: Hisanori Izuno, Yasuna Kobayashi, Noriko Kohyama, Masayuki Ohbayashi, Yutaka Sanada, Daisuke Nihei, Masako Suzuki, Toshinori YamamotoAbstract:Abstract Rat organic Solute Carrier Protein 1 (rOscp1) was isolated from a rat testis cDNA library. Isolated rOscp1 cDNA consisted of 1089 base pairs that encoded a 363-amino acid Protein, and the amino acid sequence was 88% and 93% identical to that of human OSCP1 (hOSCP1) and mouse Oscp1 (mOscp1), respectively. The message for rOscp1 is highly detected in rat testis. When expressed in X. oocytes, rOscp1 mediated the high affinity transport of p -aminohippurate (PAH) with a K m value of 15.7 ± 1.9 μM, and rOscp1-mediated organic Solutes were exhibited in time- and Na + -independent manners. rOscp1 also transported various structurally heterogenous compounds such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), and taurocholate with some differences in substrate specificity compared with hOSCP1. Immunohistochemical analysis revealed that the rOscp1 Protein is localized in the basal membrane side of Sertoli cells as observed in mouse testis [Kobayashi et al., 2007; Kobayashi, Y., Tsuchiya, A., Hayashi, T., Kohyama, N., Ohbayashi, M., Yamamoto, T., 2007. Isolation and characterization of polyspecific mouse organic Solute Carrier Protein 1 (mOscp1). Drug Metabolism and Disposition 35 (7), 1239–1245]. Thus, the present results indicate that a newly isolated cDNA clone, rOscp1, is a polyspecific organic Solute Carrier Protein with some differences in substrate specificity compared with human and mouse OSCP1.
-
isolation and characterization of polyspecific mouse organic Solute Carrier Protein 1 moscp1
Drug Metabolism and Disposition, 2007Co-Authors: Yasuna Kobayashi, Ayumi Tsuchiya, Tomofumi Hayashi, Noriko Kohyama, Masayuki Ohbayashi, Toshinori YamamotoAbstract:We succeeded in isolating the cDNA-encoding mouse organic Solute Carrier Protein 1 (mOscp1) from a mouse testis cDNA library. mOscp1 consisted of 1137 base pairs that encoded a 379-amino acid Protein, and the amino acid sequence was 85% identical to that of human OSCP1 (hOSCP1). Northern blot analysis revealed that the gene coding for mOscp1 is highly expressed in the testis, but not in other tissues. When expressed in Xenopus laevis oocytes, mOscp1 mediated the high-affinity transport of p -aminohippurate (PAH) ( K m = 18.8 ± 4.1 μM) with Na+ independence. mOscp1 transported various kinds of structurally dissimilar drugs and chemicals such as probenecid, dehydroepiandrosterone sulfate, and glutarate with some differences in substrate specificity compared with hOSCP1. Cyclophosphamide inhibited the mOscp1-mediated PAH uptake. Immunohistochemical analysis revealed that the mOscp1 Protein is localized in the plasma membrane side of Sertoli cells in the testis. Our results indicate that isolated mOscp1 is a polyspecific organic Solute Carrier Protein and may be a key molecule for the testicular handling of organic Solutes.
-
isolation and functional characterization of a novel organic Solute Carrier Protein hoscp1
Journal of Biological Chemistry, 2005Co-Authors: Yasuna Kobayashi, Noriko Kohyama, Masayuki Ohbayashi, Akiko Shibusawa, Hironori Saito, Naomi Ohshiro, Toshinori YamamotoAbstract:We succeeded in isolating a novel organic Solute Carrier from a human placenta cDNA library. The isolated cDNA consisted of 1137 base pairs that encoded a 379-amino acid Protein, hOSCP1. Northern blot and reverse transcription PCR analyses revealed that the hOSCP1 mRNA is expressed in the placenta and testis and weakly expressed in the thymus and small intestine. When expressed in Xenopus laevis oocytes, hOSCP1 mediated the high affinity transport of p-aminohippurate (PAH) (K(m) = 35.0 +/- 7.5 microm) and tetraethylammonium (K(m) = 62.3 +/- 12.2 microm) in a sodium-independent manner. However, the hOSCP1-expressing oocyte did not mediate the transport of L-carnitine. The transport of PAH by hOSCP1 was sensitive to pH, but the tetraethylammonium was not transported at the high pH examined. hOSCP1 transported prostaglandin E(2), prostaglandin F(2alpha), estrone sulfate, glutarate, L-leucine, L-ascorbic acid, and tetracycline. Thus, hOSCP1 also showed broad substrate specificity. A wide range of structurally unrelated organic compounds inhibited the hOSCP1-mediated PAH uptake. Immunohistochemical analysis revealed that the hOSCP1 Protein is localized in the basal membrane of the syncytiotrophoblast in the human placenta. Our results suggest that hOSCP1 is a novel polyspecific organic Solute Carrier Protein responsible for drug clearance from the human placenta.
Tvrtko Smital - One of the best experts on this subject based on the ideXlab platform.
-
interaction of environmental contaminants with zebrafish danio rerio multidrug and toxin extrusion Protein 7 mate7 slc47a7
Aquatic Toxicology, 2018Co-Authors: Jovica Loncar, Tvrtko SmitalAbstract:Abstract Zebrafish Mate7 belongs to Solute Carrier Protein superfamily and specifically to subfamily of multidrug and toxin extruders. It is co-orthologous to mammalian Mates, and is ubiquitously expressed in zebrafish tissues with the highest expression in kidney. It has been shown to interact with both endogenous (steroid hormones) and xenobiotic compounds (pharmaceuticals), implying a role in efflux of toxic compounds. The objective of our study was to analyse interaction of environmental contaminants with zebrafish Mate7 using a newly developed high throughput screening (HTS) Mate7 assay. A full-length zebrafish mate7 sequence was obtained from zebrafish cDNA originating from male kidney, and a stable expression of Mate7 in genetically engineered HEK293 Flp-In cells was achieved. Stable Mate7 transfectants were then used for development and optimization of a new HTS cellular uptake protocol, with DAPI and ASP + as model fluorescent substrates. The developed assay was used for identifying zebrafish Mate 7 interactors and discerning the type of interaction. A series of 89 diverse environmental contaminants, including industrial chemicals, pesticides, and pharmaceuticals, was tested and highly effective Mate7 interactors were identified in all of the aforementioned groups. Some of the inhibitors identified could be of environmental concern because they may potentially impair Mate7 efflux function, lowering the fish defence capacity against environmental contaminants, or interfering with transport of yet unidentified physiological substrates. In addition, we found significant differences between zebrafish Mate7 and mammalian Mates’ substrate preferences, a finding that should be taken into consideration when using zebrafish as a model organism in toxicokinetic studies.
Keiko Kobayashi - One of the best experts on this subject based on the ideXlab platform.
-
A difficult and complicated case study: neonatal intrahepatic cholestasis caused by citrin deficiency
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics, 2006Co-Authors: Yuan-zong Song, Keiko Kobayashi, Takeyori Saheki, Hu Hao, Miharu Ushikai, Guo-sheng Liu, Xin Xiao, Zi-neng WangAbstract:Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a kind of inborn errors of metabolism, with the main clinic manifestations of jaundice, hepatomegaly, and abnormal liver function indices. As a mitochondrial Solute Carrier Protein, citrin plays important roles in aerobic glycolysis, gluconeogenesis, urea cycle, and Protein and nucleotide syntheses. Therefore citrin deficiency causes various and complicated metabolic disturbances, such as hypoglycemia, hyperlactic acidemia, hyperammonemia, hypoProteinemia, hyperlipidemia, and galactosemia. This paper reported a case of NICCD confirmed by mutation analysis of SLC25A13, the gene encoding citrin. The baby (male, 6 months old) was referred to the First Affiliated Hospital with the complaint of jaundice of the skin and sclera, which it had suffered from for nearly 6 months. Physical examination showed obvious jaundice and a palpable liver 5 cm below the right subcostal margin. Liver function tests revealed elevated enzymatic activities, like GGT, ALP, AST, and ALT, together with increased levels of TBA, bilirubin (especially conjugated bilirubin), and decreased levels of total Protein/albumin and fibrinogen. Blood levels of ammonia, lactate, cholesterol, and triglyceride were also increased, and in particular, the serum AFP level reached 319,225.70 microg/L, a extremely elevated value that has rarely been found in practice before. Tandem mass analysis of a dried blood sample revealed increased levels of free fatty acids and tyrosine, methionine, citrulline, and threonine as well. UP-GC-MS analysis of the urine sample showed elevated galactose and galactitol. The baby was thus diagnosed with suspected NICCD based on the findings. It was then treated with oral arginine and multiple vitamins (including fat-soluble vitamins A, D, E, and K), and was fed with lactose-free and medium-chain fatty acids enriched formula instead of breast feeding. After half a month of treatment, the jaundice disappeared, and the laboratory findings, including liver function indices, blood levels of ammonia, lactate and AFP, were returned to normal level. The baby was followed up for 6 months. It developed well, and the abnormal laboratory findings, including MS-MS and UP-GC-MS analysis results, have been corrected, except a slightly elevated lactate level sometimes. SLC25A13 gene mutation analysis for the patient revealed a compound heterozygote of mutation 851del4 and 1638ins23 and therefore NICCD was definitely diagnosed.
-
Pathogenesis and Pathophysiology of Citrin (a Mitochondrial Aspartate Glutamate Carrier) Deficiency
Metabolic Brain Disease, 2002Co-Authors: Takeyori Saheki, Mikio Iijima, Keiko Kobayashi, Ikumi Nishi, Tomotsugu Yasuda, Naoki Yamaguchi, Hong Zhi Gao, Md. Abdul Jalil, Laila BegumAbstract:Adult-onset type II citrullinemia (CTLN2), characterized by a liver-specific deficiency of urea cycle enzyme, argininosuccinate synthetase, is caused by mutations in SLC25A13 that encodes a calcium binding mitochondrial Solute Carrier Protein, citrin. Citrin deficiency causes not only CTLN2 but also neonatal intrahepatic cholestasis caused by citrin deficiency at neonatal period. Moreover citrin and its isoform aralar were found to be aspartate glutamate Carrier. From the viewpoint of the metabolic functions of citrin as aspartate glutamate Carrier in urea synthesis and NADH shuttle, symptoms of CTLN2 and neonatal intrahepatic cholestasis caused by citrin deficiency are analyzed.
-
mitochondrial aspartate glutamate Carrier citrin deficiency as the cause of adult onset type ii citrullinemia ctln2 and idiopathic neonatal hepatitis niccd
Journal of Human Genetics, 2002Co-Authors: Takeyori Saheki, Keiko KobayashiAbstract:By using homozygosity mapping and positional cloning, we have shown that adult-onset type II citrullinemia (CTLN2) is caused by mutations of the SLC25A13 gene, which is localized on chromosome 7q21.3 and encodes a mitochondrial Solute Carrier Protein named citrin. So far, we have reported nine mutations, most of which cause loss of citrin, and we have established several methods for DNA diagnosis. These methods have shown that more than 90% of the patients diagnosed as suffering from CTLN2 by enzymatic analysis carry SLC25A13 mutations in both alleles, indicating that CTLN2 is caused by citrin deficiency. Furthermore, by using the same DNA diagnosis methods, we discovered that 70 neonates or infants suffering from a particular type of neonatal hepatitis carry the same SLC25A13 mutations. Since the symptoms of the neonates are different from those of the more severe CTLN2 and usually ameliorate without special treatment, we designated the neonatal disease neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). We conclude that citrin deficiency causes NICCD in neonates and CTLN2 in adults through the additional effects of genetic or environmental modifiers. Since the function of citrin, together with that of an isoform, aralar, was found to be as a mitochondrial aspartate glutamate Carrier, the various symptoms of NICCD and CTLN2 may be understood as caused by defective aspartate export from the mitochondria to the cytosol and defects in the malate aspartate shuttle. It is, however, still difficult to understand the cause of the hepatic deficiency of argininosuccinate synthetase Protein in CTLN2.
Takeyori Saheki - One of the best experts on this subject based on the ideXlab platform.
-
A difficult and complicated case study: neonatal intrahepatic cholestasis caused by citrin deficiency
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics, 2006Co-Authors: Yuan-zong Song, Keiko Kobayashi, Takeyori Saheki, Hu Hao, Miharu Ushikai, Guo-sheng Liu, Xin Xiao, Zi-neng WangAbstract:Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a kind of inborn errors of metabolism, with the main clinic manifestations of jaundice, hepatomegaly, and abnormal liver function indices. As a mitochondrial Solute Carrier Protein, citrin plays important roles in aerobic glycolysis, gluconeogenesis, urea cycle, and Protein and nucleotide syntheses. Therefore citrin deficiency causes various and complicated metabolic disturbances, such as hypoglycemia, hyperlactic acidemia, hyperammonemia, hypoProteinemia, hyperlipidemia, and galactosemia. This paper reported a case of NICCD confirmed by mutation analysis of SLC25A13, the gene encoding citrin. The baby (male, 6 months old) was referred to the First Affiliated Hospital with the complaint of jaundice of the skin and sclera, which it had suffered from for nearly 6 months. Physical examination showed obvious jaundice and a palpable liver 5 cm below the right subcostal margin. Liver function tests revealed elevated enzymatic activities, like GGT, ALP, AST, and ALT, together with increased levels of TBA, bilirubin (especially conjugated bilirubin), and decreased levels of total Protein/albumin and fibrinogen. Blood levels of ammonia, lactate, cholesterol, and triglyceride were also increased, and in particular, the serum AFP level reached 319,225.70 microg/L, a extremely elevated value that has rarely been found in practice before. Tandem mass analysis of a dried blood sample revealed increased levels of free fatty acids and tyrosine, methionine, citrulline, and threonine as well. UP-GC-MS analysis of the urine sample showed elevated galactose and galactitol. The baby was thus diagnosed with suspected NICCD based on the findings. It was then treated with oral arginine and multiple vitamins (including fat-soluble vitamins A, D, E, and K), and was fed with lactose-free and medium-chain fatty acids enriched formula instead of breast feeding. After half a month of treatment, the jaundice disappeared, and the laboratory findings, including liver function indices, blood levels of ammonia, lactate and AFP, were returned to normal level. The baby was followed up for 6 months. It developed well, and the abnormal laboratory findings, including MS-MS and UP-GC-MS analysis results, have been corrected, except a slightly elevated lactate level sometimes. SLC25A13 gene mutation analysis for the patient revealed a compound heterozygote of mutation 851del4 and 1638ins23 and therefore NICCD was definitely diagnosed.
-
Pathogenesis and Pathophysiology of Citrin (a Mitochondrial Aspartate Glutamate Carrier) Deficiency
Metabolic Brain Disease, 2002Co-Authors: Takeyori Saheki, Mikio Iijima, Keiko Kobayashi, Ikumi Nishi, Tomotsugu Yasuda, Naoki Yamaguchi, Hong Zhi Gao, Md. Abdul Jalil, Laila BegumAbstract:Adult-onset type II citrullinemia (CTLN2), characterized by a liver-specific deficiency of urea cycle enzyme, argininosuccinate synthetase, is caused by mutations in SLC25A13 that encodes a calcium binding mitochondrial Solute Carrier Protein, citrin. Citrin deficiency causes not only CTLN2 but also neonatal intrahepatic cholestasis caused by citrin deficiency at neonatal period. Moreover citrin and its isoform aralar were found to be aspartate glutamate Carrier. From the viewpoint of the metabolic functions of citrin as aspartate glutamate Carrier in urea synthesis and NADH shuttle, symptoms of CTLN2 and neonatal intrahepatic cholestasis caused by citrin deficiency are analyzed.
-
mitochondrial aspartate glutamate Carrier citrin deficiency as the cause of adult onset type ii citrullinemia ctln2 and idiopathic neonatal hepatitis niccd
Journal of Human Genetics, 2002Co-Authors: Takeyori Saheki, Keiko KobayashiAbstract:By using homozygosity mapping and positional cloning, we have shown that adult-onset type II citrullinemia (CTLN2) is caused by mutations of the SLC25A13 gene, which is localized on chromosome 7q21.3 and encodes a mitochondrial Solute Carrier Protein named citrin. So far, we have reported nine mutations, most of which cause loss of citrin, and we have established several methods for DNA diagnosis. These methods have shown that more than 90% of the patients diagnosed as suffering from CTLN2 by enzymatic analysis carry SLC25A13 mutations in both alleles, indicating that CTLN2 is caused by citrin deficiency. Furthermore, by using the same DNA diagnosis methods, we discovered that 70 neonates or infants suffering from a particular type of neonatal hepatitis carry the same SLC25A13 mutations. Since the symptoms of the neonates are different from those of the more severe CTLN2 and usually ameliorate without special treatment, we designated the neonatal disease neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). We conclude that citrin deficiency causes NICCD in neonates and CTLN2 in adults through the additional effects of genetic or environmental modifiers. Since the function of citrin, together with that of an isoform, aralar, was found to be as a mitochondrial aspartate glutamate Carrier, the various symptoms of NICCD and CTLN2 may be understood as caused by defective aspartate export from the mitochondria to the cytosol and defects in the malate aspartate shuttle. It is, however, still difficult to understand the cause of the hepatic deficiency of argininosuccinate synthetase Protein in CTLN2.
Yasuna Kobayashi - One of the best experts on this subject based on the ideXlab platform.
-
genetic polymorphism of the human organic Solute Carrier Protein 1 hoscp1 gene in japanese patients with non viral liver carcinoma
Meta Gene, 2014Co-Authors: Mayumi Toda, Yasuna Kobayashi, Noriko Kohyama, Masayuki Ohbayashi, Tomotake Koizumi, Koji Saito, Takeshi Aoki, Masahiko Murakami, Hajime Yasuhara, Toshinori YamamotoAbstract:Human organic Solute Carrier Protein 1 (hOSCP1) is a Na+-independent multispecific organic Solute transporter. To date, several studies have revealed that gene mutations of the transporters are likely to be associated with some diseases; however, there are no data concerning the genetic polymorphism of the hOSCP1 gene in Japanese patients with non-viral liver carcinoma (LC). In the present study, we isolated genomic DNA from a normal portion of LC, and analyzed 41 single nucleotide polymorphisms (SNPs) chosen from a database of SNPs (dbSNPs). We found genotype frequencies for 2 non-synonymous SNPs [rs34409118 (Thr131 → Ala) and rs1416840 (Ile219 → Thr)] and 1 synonymous SNP [rs16822954 (Ser193 → Ser)] to be statistically significant when compared with dbSNPs. No statistical significance was observed in rs2275477 (Gly307 → Arg) in the hOSCP1 gene. With respect to the allele frequency, we also observed rs34409118 to be statistically significant. Interestingly, we found that non-viral LC patients do not carry heterozygous mutations in rs1416840 (A/G) and rs16822954 (A/G), suggesting that a non-Carrier of heterozygous mutations in these two SNPs might be a biomarker for susceptibility for non-viral LC in Japanese. Further analyses of patients with hOSCP1 variants may elucidate the relationship between the hOSCP1 gene and susceptibility of non-viral LC in Japanese patients.
-
rat organic Solute Carrier Protein 1 roscp1 mediated the transport of organic Solutes in xenopus laevis oocytes isolation and pharmacological characterization of roscp1
Life Sciences, 2007Co-Authors: Hisanori Izuno, Yasuna Kobayashi, Noriko Kohyama, Masayuki Ohbayashi, Yutaka Sanada, Daisuke Nihei, Masako Suzuki, Toshinori YamamotoAbstract:Abstract Rat organic Solute Carrier Protein 1 (rOscp1) was isolated from a rat testis cDNA library. Isolated rOscp1 cDNA consisted of 1089 base pairs that encoded a 363-amino acid Protein, and the amino acid sequence was 88% and 93% identical to that of human OSCP1 (hOSCP1) and mouse Oscp1 (mOscp1), respectively. The message for rOscp1 is highly detected in rat testis. When expressed in X. oocytes, rOscp1 mediated the high affinity transport of p -aminohippurate (PAH) with a K m value of 15.7 ± 1.9 μM, and rOscp1-mediated organic Solutes were exhibited in time- and Na + -independent manners. rOscp1 also transported various structurally heterogenous compounds such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), and taurocholate with some differences in substrate specificity compared with hOSCP1. Immunohistochemical analysis revealed that the rOscp1 Protein is localized in the basal membrane side of Sertoli cells as observed in mouse testis [Kobayashi et al., 2007; Kobayashi, Y., Tsuchiya, A., Hayashi, T., Kohyama, N., Ohbayashi, M., Yamamoto, T., 2007. Isolation and characterization of polyspecific mouse organic Solute Carrier Protein 1 (mOscp1). Drug Metabolism and Disposition 35 (7), 1239–1245]. Thus, the present results indicate that a newly isolated cDNA clone, rOscp1, is a polyspecific organic Solute Carrier Protein with some differences in substrate specificity compared with human and mouse OSCP1.
-
isolation and characterization of polyspecific mouse organic Solute Carrier Protein 1 moscp1
Drug Metabolism and Disposition, 2007Co-Authors: Yasuna Kobayashi, Ayumi Tsuchiya, Tomofumi Hayashi, Noriko Kohyama, Masayuki Ohbayashi, Toshinori YamamotoAbstract:We succeeded in isolating the cDNA-encoding mouse organic Solute Carrier Protein 1 (mOscp1) from a mouse testis cDNA library. mOscp1 consisted of 1137 base pairs that encoded a 379-amino acid Protein, and the amino acid sequence was 85% identical to that of human OSCP1 (hOSCP1). Northern blot analysis revealed that the gene coding for mOscp1 is highly expressed in the testis, but not in other tissues. When expressed in Xenopus laevis oocytes, mOscp1 mediated the high-affinity transport of p -aminohippurate (PAH) ( K m = 18.8 ± 4.1 μM) with Na+ independence. mOscp1 transported various kinds of structurally dissimilar drugs and chemicals such as probenecid, dehydroepiandrosterone sulfate, and glutarate with some differences in substrate specificity compared with hOSCP1. Cyclophosphamide inhibited the mOscp1-mediated PAH uptake. Immunohistochemical analysis revealed that the mOscp1 Protein is localized in the plasma membrane side of Sertoli cells in the testis. Our results indicate that isolated mOscp1 is a polyspecific organic Solute Carrier Protein and may be a key molecule for the testicular handling of organic Solutes.
-
isolation and functional characterization of a novel organic Solute Carrier Protein hoscp1
Journal of Biological Chemistry, 2005Co-Authors: Yasuna Kobayashi, Noriko Kohyama, Masayuki Ohbayashi, Akiko Shibusawa, Hironori Saito, Naomi Ohshiro, Toshinori YamamotoAbstract:We succeeded in isolating a novel organic Solute Carrier from a human placenta cDNA library. The isolated cDNA consisted of 1137 base pairs that encoded a 379-amino acid Protein, hOSCP1. Northern blot and reverse transcription PCR analyses revealed that the hOSCP1 mRNA is expressed in the placenta and testis and weakly expressed in the thymus and small intestine. When expressed in Xenopus laevis oocytes, hOSCP1 mediated the high affinity transport of p-aminohippurate (PAH) (K(m) = 35.0 +/- 7.5 microm) and tetraethylammonium (K(m) = 62.3 +/- 12.2 microm) in a sodium-independent manner. However, the hOSCP1-expressing oocyte did not mediate the transport of L-carnitine. The transport of PAH by hOSCP1 was sensitive to pH, but the tetraethylammonium was not transported at the high pH examined. hOSCP1 transported prostaglandin E(2), prostaglandin F(2alpha), estrone sulfate, glutarate, L-leucine, L-ascorbic acid, and tetracycline. Thus, hOSCP1 also showed broad substrate specificity. A wide range of structurally unrelated organic compounds inhibited the hOSCP1-mediated PAH uptake. Immunohistochemical analysis revealed that the hOSCP1 Protein is localized in the basal membrane of the syncytiotrophoblast in the human placenta. Our results suggest that hOSCP1 is a novel polyspecific organic Solute Carrier Protein responsible for drug clearance from the human placenta.