Enzymatic Properties, Tissue-Specific Expression, and Lysosomal Location of Two Highly Homologous Rat SULT1C2 Sulfotransferases

Li, Xiangrong; Jöhnk, Claudia; Hartmann, Dieter; Schestag, Frank; Kromer, W.; Gieselmann, Volkmar

doi:10.1006/bbrc.2000.2744

Cited by 17 publications

(16 citation statements)

References 15 publications

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“…28) Sulfation of xanthurenic acid occurred in various tissues including the liver, stomach, jejunum, colon, and kidney, and sulfotransferase SULT1C2 was exhibited to be predominantly expressed in the proximal tubule, where OAT1 and OAT3 work. 29,30) Accordingly, it is intriguing whether the formation of xanthurenic acid sulfate followed by its tubular uptake by OAT1 and OAT3 is responsible for diuresis.…”

Section: Discussionmentioning

confidence: 99%

Transport of Xanthurenic Acid by Rat/Human Organic Anion Transporters OAT1 and OAT3

Uwai

Honjo

2013

Bioscience, Biotechnology, and Biochemistry

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Kynurenic acid, a tryptophan metabolite, is involved in psychiatric disease. Our laboratory previously described its transport by rat/human organic anion transporters rOAT1, hOAT1, rOAT3 and hOAT3, which are involved in drug disposition. In this study, we performed an uptake experiment using Xenopus laevis oocytes to examine the transport of xanthurenic acid, a tryptophan catabolite and kynurenic acid analog, by various transporters. All the transporters tested stimulated the uptake of xanthurenic acid into oocytes. The transport activity of xanthurenic acid by hOAT1 was greater than that by rOAT1. In OAT3, the rat homolog showed efficient transport, compared with hOAT3. The apparent values of K m and V max for the transport by hOAT1 were 4.83 M and 26.0 pmol/ oocyte/h respectively. In rOAT3, the respective values were 6.87 M and 21.7 pmol/oocyte/h. This is the first report on xanthurenic acid transport by OAT1 and OAT3.

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Section: Discussionmentioning

confidence: 99%

Transport of Xanthurenic Acid by Rat/Human Organic Anion Transporters OAT1 and OAT3

Uwai

Honjo

2013

Bioscience, Biotechnology, and Biochemistry

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“…RACE-ready cDNA was prepared from 750 ng of high quality RNA, and the 59-end of SULT1C2 was then amplified using the Advantage 2 PCR kit (Clontech Laboratories) and gene-specific reverse primers. Due to a high sequence homology with SULT1C2A in the coding region (Xiangrong et al, 2000), two different SULT1C2-specific reverse primers were designed targeting noncoding exon 3 of the reference sequence (NM_133547.4) and are as follows: primer 1, 59-CCCTGCA CAACAGAACAGAAGGCTG-39; and primer 2, 59-GGAGGGATGCT TTCCCCTAGCCTCT-39. After amplification, the PCR products were resolved on agarose gels containing ethidium bromide, and individual bands were extracted and purified using the QiaQuick Gel Purification kit (Qiagen).…”

Section: Methodsmentioning

confidence: 99%

“…The SULT1C2 gene is localized to chromosome 2q11.2 in humans, 9q11 in rats, and 17 in mice, and orthologs have been cloned, expressed, and partially characterized (Freimuth et al, 2000;Xiangrong et al, 2000;Sugimura et al, 2002). SULT1C2 mRNA has been detected in a variety of human tissues, including liver, kidney, thyroid, stomach, and intestine (Her et al, 1997;Dooley et al, 2000;Stanley et al, 2005), whereas in rodents mRNA is predominately expressed in the kidneys, stomach, and liver (Xiangrong et al, 2000;Alnouti and Klaassen, 2006). SULT1C2 catalyzes the sulfonation of the prototypical substrate p-nitrophenol as well as the procarcinogen N-hydroxy-2-acetylaminofluorene, suggesting a role in chemical carcinogenesis (Sakakibara et al, 1998;Xiangrong et al, 2000;Allali-Hassani et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…SULT1C2 mRNA has been detected in a variety of human tissues, including liver, kidney, thyroid, stomach, and intestine (Her et al, 1997;Dooley et al, 2000;Stanley et al, 2005), whereas in rodents mRNA is predominately expressed in the kidneys, stomach, and liver (Xiangrong et al, 2000;Alnouti and Klaassen, 2006). SULT1C2 catalyzes the sulfonation of the prototypical substrate p-nitrophenol as well as the procarcinogen N-hydroxy-2-acetylaminofluorene, suggesting a role in chemical carcinogenesis (Sakakibara et al, 1998;Xiangrong et al, 2000;Allali-Hassani et al, 2007). Additionally, sulfonation of iodothyronines, which reduces receptor binding affinity and accelerates deiodination, has been reported (Li et al, 2000;Strott, 2002;Allali-Hassani et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional Regulation of Cytosolic Sulfotransferase 1C2 by Intermediates of the Cholesterol Biosynthetic Pathway in Primary Cultured Rat Hepatocytes

Rondini

Pant

Kocarek

2015

J Pharmacol Exp Ther

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Cytosolic sulfotransferase 1C2 (SULT1C2) is expressed in the kidney, stomach, and liver of rats; however, the mechanisms regulating expression of this enzyme are not known. We evaluated transcriptional regulation of SULT1C2 by mevalonate (MVA)-derived intermediates in primary cultured rat hepatocytes using several cholesterol synthesis inhibitors. Blocking production of mevalonate with the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor pravastatin (30 mM), reduced SULT1C2 mRNA content by ∼40% whereas the squalene synthase inhibitor squalestatin (SQ1, 0.1 mM), which causes accumulation of nonsterol isoprenoids, increased mRNA content by 4-fold. Treatment with MVA (10 mM) strongly induced SULT1C2 mRNA by 12-fold, and this effect was blocked by inhibiting squalene epoxidase but not by more distal cholesterol inhibitors, indicating the effects of MVA are mediated by postsqualene metabolites. Using rapid amplification of cDNA ends (RACE), we characterized the 59 end of SULT1C2 mRNA and used this information to generate constructs for promoter analysis. SQ1 and MVA increased reporter activity by ∼1.6-and 3-fold, respectively, from a construct beginning 49 base pairs (bp) upstream from the longest 59-RACE product (-3140:-49). Sequence deletions from this construct revealed a hepatocyte nuclear factor 1 (HNF1) element (-2558), and mutation of this element reduced basal (75%) and MVA-induced (30%) reporter activity and attenuated promoter activation following overexpression of HNF1a or 1b. However, the effects of SQ1 were localized to a more proximal promoter region (-281:-49). Collectively, our findings demonstrate that cholesterol biosynthetic intermediates influence SULT1C2 expression in rat primary hepatocytes. Further, HNF1 appears to play an important role in mediating basal and MVA-induced SULT1C2 transcription.

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“…It was shown that sulfotransferase for xanthurenic acid is expressed in the epithelial cells of the proximal tubules, and that the kidney has the ability to conjugate xanthurenic acid with sulfate (4,8). Accordingly, it is considered that the sulfation of xanthurenic acid followed by the OAT1-mediated Fig.…”

Section: Referencesmentioning

confidence: 99%

Diuresis by intravenous administration of xanthurenic acid in rats, and inhibition by probenecid

et al. 2014

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The conjugates with sulfate and glucoside of xanthurenic acid, a tryptophan metabolite, were reported to show natriuresis. Sulfotransferase for xanthurenic acid works in the renal proximal tubule to produce the sulfate of xanthurenic acid as well as the liver, and we recently found that xanthurenic acid is a substrate of renal organic anion transporter OAT1. The purpose of this study was to examine relationship between the transport by OAT1 and diuresis related with xanthurenic acid. Drug transport experiment using Xenopus laevis oocytes represented that probenecid inhibited xanthurenic acid uptake by rat OAT1 (rOAT1). Although no diuresis was recognized by the intravenous injection of xanthurenic acid as a bolus in rats, the addition of its infusion exhibited natriuresis. Simultaneous administration of probenecid significantly decreased the urine volume and excreted amounts of sodium into urine. These findings showed the diuresis by the xanthurenic acid administration, and it was probenecid-sensitive. The rOAT1-mediated transport of xanthurenic acid might, at least in part, contribute to its diuretic effect.In the renal proximal tubules, organic anion transporters secrete endogenous metabolites, drugs, and xenobiotics into urine. From the mid-1990s, cDNA of renal organic anion transporters has been isolated, and its function and expression have been characterized. Organic anion transporters OAT1 and OAT3 are thought to be responsible for the renal tubular uptake of organic anions from blood, and multidrug resistance-associated protein MRP4 is the strong candidate mediating their efflux into lumen (2). Our laboratory has been interested in transport of bioactive substances by OAT1 and OAT3. Recently, we examined interaction of the metabolites of the kynurenine pathway, a main route for the tryptophan metabolism, with OAT1 and OAT3, and represented that kynurenic acid and xanthurenic acid were transported by them (5, 6). Kynurenic acid antagonizes N-methyl D-aspartate (NMDA) receptor in the brain under physiological conditions, and is accepted as the key molecule in several psychiatric disorders (3). Xanthurenic acid is closely structurally related to kynurenic acid (Fig.

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Enzymatic Properties, Tissue-Specific Expression, and Lysosomal Location of Two Highly Homologous Rat SULT1C2 Sulfotransferases

Cited by 17 publications

References 15 publications

Transport of Xanthurenic Acid by Rat/Human Organic Anion Transporters OAT1 and OAT3

Transport of Xanthurenic Acid by Rat/Human Organic Anion Transporters OAT1 and OAT3

Transcriptional Regulation of Cytosolic Sulfotransferase 1C2 by Intermediates of the Cholesterol Biosynthetic Pathway in Primary Cultured Rat Hepatocytes

Diuresis by intravenous administration of xanthurenic acid in rats, and inhibition by probenecid

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