Purification, Characterization, and Molecular Cloning of A Novel Rat Liver Dopa/Tyrosine Sulfotransferase

Sakakibara, Yoichi; Yasuda, Takami; Zwieb, Christian W; Nakayama, Tatsuo; Suiko, Masahito; Nakajima, Hiroshi; Liu, Ming Cheh

doi:10.1074/jbc.270.51.30470

Cited by 44 publications

(15 citation statements)

References 60 publications

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“…In contrast, SULT-N has only recently been described, and its activity as a T 4 sulfotransferase has not been elucidated. However, the fact that SULT-N is closely related to SULT1A1 (35) suggests that this enzyme will have similar substrate specificity. Finally, SULT2A1 has recently been shown to exhibit low K m values for TH relative to other members of the human SULT family and is known to contribute to triiodothyronine sulfation (36).…”

Section: Discussionmentioning

confidence: 99%

The Nuclear Receptor CAR Is a Regulator of Thyroid Hormone Metabolism during Caloric Restriction

Maglich

Watson

McMillen

et al. 2004

Journal of Biological Chemistry

209

192

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The orphan nuclear receptor CAR (NR1I3) has been characterized as a central component in the coordinate response to xenobiotic and endobiotic stress. In this study, we demonstrate that CAR plays a pivotal function in energy homeostasis and establish an unanticipated metabolic role for this nuclear receptor. Wild-type mice treated with the synthetic CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) exhibited decreased serum concentration of the thyroid hormone (TH) thyroxine (T 4 ). However, treatment of Car ؊/؊ mice with TCPOBOP failed to elicit these changes. To examine whether CAR played a role in the regulation of TH levels under physiological conditions, wild-type and Car ؊/؊ mice were fasted for 24 h, a process known to alter TH metabolism in mammals. As expected, the serum triiodothyronine and T 4 concentrations decreased in wild-type mice. However, triiodothyronine and T 4 levels in fasted Car ؊/؊ mice remained significantly higher than those in fasted wild-type animals. Concomitant with the changes in serum TH levels, both CAR agonist treatment and fasting induced the expression of CAR target genes (notably, Cyp2b10, Ugt1a1, Sultn, Sult1a1, and Sult2a1) in a receptor-dependent manner. Importantly, the Ugt1a1, Sultn, Sult1a1, and Sult2a1 genes encode enzymes that are capable of metabolizing TH. An attenuated reduction in TH levels during fasting, as observed in Car ؊/؊ mice, would be predicted to increase weight loss during caloric restriction. Indeed, when Car ؊/؊ animals were placed on a 40% caloric restriction diet for 12 weeks, Car ؊/؊ animals lost over twice as much weight as their wild-type littermates. Thus, CAR participates in the molecular mechanisms contributing to homeostatic resistance to weight loss. These data imply that CAR represents a novel therapeutic target to uncouple metabolic rate from food intake and has implications in obesity and its associated disorders.In Western societies, obesity is reaching potentially epidemic proportions. In the United States, it is estimated that 55% of adults are overweight, and nearly a quarter are obese (1). Associated with the rise in obesity are concomitant rises in the incidence of metabolic syndrome or syndrome X, typified by type 2 diabetes, cardiovascular disease, hypertension, and hyperlipidemia. The epidemic of obesity inflicts significant disadvantages on both the individual and society, i.e. increased risk of death and disease, increased health care costs, and reduced social and educational status.A significant and discouraging factor for obese individuals trying to lose weight is that homeostatic resistance mechanisms operate to resist weight loss (2, 3). A major homeostatic barrier is decreased basal metabolic rate during periods of reduced caloric intake. Thyroid hormones (THs) 1 (thyroxine (T 4 ) and triiodothyronine (T 3 )) are the predominant regulators of basal metabolic rate. Serum levels of TH show a direct correlation with energy expenditure and caloric loss (4), decreasing significantly during fasting. The most potent...

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Section: Discussionmentioning

confidence: 99%

The Nuclear Receptor CAR Is a Regulator of Thyroid Hormone Metabolism during Caloric Restriction

Maglich

Watson

McMillen

et al. 2004

Journal of Biological Chemistry

209

192

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“…rSULT1A1, -1B1, -1C1, and -1E1 show 79, 74, 63, and 70% amino acid sequence identity, respectively, with their human homologs, and ϳ50% identity among themselves. Sulfation of T 3 by rat SULT1B1 and -1C1 has been reported previously (12,19,37,44). In this study, we compared kinetic parameters and substrate specificities for the different rat enzymes with these characteristics for female rat liver and male rat liver, kidney, and brain cytosol in an attempt to determine which enzyme forms are involved in iodothyronine sulfation in the different tissues.…”

Section: Discussionmentioning

confidence: 99%

Characterization of rat iodothyronine sulfotransferases

Kester¹,

Kaptein²,

Roest³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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Sulfation appears to be an important pathway for the reversible inactivation of thyroid hormone during fetal development. The rat is an often used animal model to study the regulation of fetal thyroid hormone status. The present study was done to determine which sulfotransferases (SULTs) are important for iodothyronine sulfation in the rat, using radioactive T 4, T3, rT3, and 3,3Ј-T2 as substrates, 3Ј-phosphoadenosine-5Ј-phosphosulfate (PAPS) as cofactor, and rat liver, kidney and brain cytosol, and recombinant rat SULT1A1, -1B1, -1C1, -1E1, -2A1, -2A2, and -2A3 as enzymes. Recombinant rat SULT1A1, -1E1, -2A1, -2A2, and -2A3 failed to catalyze iodothyronine sulfation. For all tissue SULTs and for rSULT1B1 and rSULT1C1, 3,3Ј-T 2 was by far the preferred substrate. Apparent K m values for 3,3Ј-T2 amounted to 1.9 M in male liver, 4.4 M in female liver, 0.76 M in male kidney, 0.23 M in male brain, 7.7 M for SULT1B1, and 0.62 M for SULT1C1, whereas apparent K m values for PAPS showed less variation (2.0-6.9 M). Sulfation of 3,3Ј-T 2 was inhibited dose dependently by other iodothyronines, with similar structure-activity relationships for most enzymes except for the SULT activity in rat brain. The apparent K m values of 3,3Ј-T2 in liver cytosol were between those determined for SULT1B1 and -1C1, supporting the importance of these enzymes for the sulfation of iodothyronines in rat liver, with a greater contribution of SULT1C1 in male than in female rat liver. The results further suggest that rSULT1C1 also contributes to iodothyronine sulfation in rat kidney, whereas other, yet-unidentified forms appear more important for the sulfation of thyroid hormone in rat brain. thyroid hormone; sulfation; rat sulfotransferase 1B1; rat sulfotransferase 1C1 SULFATION IS A METABOLIC REACTION that facilitates the excretion of endogenous and exogenous hydrophobic compounds in bile and urine by increasing their water solubility (5,9,16,35). Biliary excretion of iodothyronines is also increased by sulfation. More importantly, however, sulfation appears to be a key step in the inactivation of thyroid hormone. The prohormone thyroxine (T 4 ) is converted by outer-ring deiodination (ORD) to the biologically active 3,3Ј,5-triiodothyronine (T 3 ) or by inner-ring deiodination (IRD) to the inactive 3,3Ј,5Ј-triiodothyronine (rT 3 ) (42). By sulfation, T 3 loses its affinity for the thyroid hormone receptors (41). Additionally, T 3 sulfate (T 3 S) is subject to accelerated degradation, as sulfation facilitates the IRD of T 3 by the type I deiodinase (D1) (42). Sulfation also facilitates the inactivating IRD of T 4 by D1, whereas the activating ORD of T 4 by D1 is completely blocked by sulfation (42). Therefore, an important function of sulfation is to facilitate the irreversible degradation of thyroid hormone. Furthermore, under conditions in which the deiodinative clearance of sulfates is impaired, sulfation may be reversed by sulfatases. Because T 3 S and T 4 S levels in the human fetal circulation are high (4, 38, 40), it has been speculated ...

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“…Similarly, the expression of SULT1 family members was differentially affected by PB treatment [61]. PB suppressed SULT1A1 mRNA levels by ~58%, while the amount of mRNA encoding the dopa-tyrosine SULT1B enzyme [63] increased to ~417% of control [61]. The mRNA levels of rat hepatic SULT1E1 [64] and SULT1C1, an enzyme active in the metabolism of N-hydroxy-2-acetylaminofluorene [65], did not change significantly following PB treatment [61].…”

Section: Sult Regulation By the Xenobiotic-sensing Receptors Pxr Andmentioning

confidence: 99%

Regulation of Sulfotransferases by Xenobiotic Receptors

Runge‐Morris¹,

Ta²

2005

CDM

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The transcription factor networks that regulate basal and xenobiotic-modulated expression of the hepatic sulfotransferases affect the dynamics of xenobiotic detoxication, carcinogen bioactivation and metabolic homeostasis. Emerging evidence suggests that liver-enriched transcription factors, the aryl hydrocarbon (Ah) receptor and members of the nuclear receptor transcription factor superfamily all play integrated roles in the control of sulfotransferase gene transcription. Unlike the well known up-regulation of CYP1A1, expression of rat hepatic aryl (SULT1A1) and hydroxysteroid (SULT2A) sulfotransferase is suppressed in response to treatment with the prototypic Ah receptor ligand, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. Glucocorticoid-inducible rat hepatic SULT1A1 gene transcription occurs through a glucocorticoid receptor (GR)-mediated mechanism, while human hepatic SULT1A1 does not display GR-inducible expression. By comparison, liver-enriched transcription factors, such as CCAAT/enhancer binding protein, are essential for the maintenance of basal and GR-inducible rat hepatic SULT2A expression. The transcriptional control of rodent and human hepatic SULT2A expression is subject to trans-activation by the environmental sensor, pregnane X receptor (PXR). IR0 (inverted repeat with zero intervening bases) motifs located in the 5'-flanking regions of rodent SULT2A genes are required for transcriptional activation by PXR and other nuclear receptors, including constitutive androstane receptor, farnesoid X receptor and vitamin D receptor. Peroxisome proliferator activated receptor alpha (PPARalpha) mediates the induction of human, but not rat, hepatic SULT2A gene transcription, thus implicating a role for fatty acids as endogenous regulators of hepatic sulfonation in humans. This review focuses on the xenobiotic sensors and transcription factor systems that regulate sulfotransferase gene expression.

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Purification, Characterization, and Molecular Cloning of A Novel Rat Liver Dopa/Tyrosine Sulfotransferase

Cited by 44 publications

References 60 publications

The Nuclear Receptor CAR Is a Regulator of Thyroid Hormone Metabolism during Caloric Restriction

The Nuclear Receptor CAR Is a Regulator of Thyroid Hormone Metabolism during Caloric Restriction

Characterization of rat iodothyronine sulfotransferases

Regulation of Sulfotransferases by Xenobiotic Receptors

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