Redox regulation of human estrogen sulfotransferase (hSULT1E1)

Maiti, Smarajit; Zhang, Jimei; Chen, Guangping

doi:10.1016/j.bcp.2006.12.026

Cited by 31 publications

(36 citation statements)

References 38 publications

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“…Oxidative regulation of the catalytic activity of cytosolic sulfotransferases has been demonstrated in family 1 SULTs, including members of both SULT1A, as well as SULT1E subfamilies (Marshall et al, 1997;Maiti et al, 2005Maiti et al, , 2007. Our results from the present study indicate that the catalytic activity of hSULT2A1, an important member of the SULT2 family in humans, can also be modulated through oxidation at cysteine residues.…”

Section: Discussionsupporting

confidence: 61%

“…Since the reversibility of oxidative modification of family 1 SULTs has been previously demonstrated (Maiti et al, 2007), we sought to determine the reversibility of disulfide bond formation in hSULT2A1. Following a 1-hour treatment of hSULT2A1 with 0.5 mM diamide or 0.5 mM Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Although the various isoforms often have distinct, but overlapping, specificities for substrates and inhibitors, it is becoming increasingly apparent that other factors, such as the redox environment of these enzymes, can have additional effects on catalysis. For example, several family 1 SULTs are sensitive to oxidants that cause the formation of disulfide bonds (Marshall et al, 1997(Marshall et al, , 2000Duffel et al, 2001;Maiti et al, 2005Maiti et al, , 2007Liu et al, 2011;Dammanahalli and Duffel, 2012). Moreover, it is clear that, in addition to the rates of catalysis, substrate specificity may be altered by disulfide bond formation in family 1 SULTs (Marshall et al, 2000;Duffel et al, 2001;Liu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Modification of the Catalytic Function of Human Hydroxysteroid Sulfotransferase hSULT2A1 by Formation of Disulfide Bonds

Qin¹,

Teesch²,

Duffel³

2013

Drug Metab Dispos

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The human cytosolic sulfotransferase hSULT2A1 catalyzes the sulfation of a broad range of xenobiotics, as well as endogenous hydroxysteroids and bile acids. Reversible modulation of the catalytic activity of this enzyme could play important roles in its physiologic functions. Whereas other mammalian sulfotransferases are known to be reversibly altered by changes in their redox environment, this has not been previously shown for hSULT2A1. We have examined the hypothesis that the formation of disulfide bonds in hSULT2A1 can reversibly regulate the catalytic function of the enzyme. Three thiol oxidants were used as model compounds to investigate their effects on homogeneous preparations of hSULT2A1: glutathione disulfide, 5,59-dithiobis(2-nitrobenzoic acid), and 1,1'-azobis(N,N-dimethylformamide) (diamide). Examination of the effects of disulfide bond formation with these agents indicated that the activity of the enzyme is reversibly altered. Studies on the kinetics of the hSULT2A1-catalyzed sulfation of dehydroepiandrosterone (DHEA) showed the effects of disulfide bond formation on the substrate inhibition characteristics of the enzyme. The effects of these agents on the binding of substrates and products, liquid chromatography-mass spectrometry identification of the disulfides formed, and structural modeling of the modified enzyme were examined. Our results indicate that conformational changes at cysteines near the nucleotide binding site affect the binding of both the nucleotide and DHEA to the enzyme, with the specific effects dependent on the structure of the resulting disulfide. Thus, the formation of disulfide bonds in hSULT2A1 is a potentially important reversible mechanism for alterations in the rates of sulfation of both endogenous and xenobiotic substrates.

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Section: Discussionsupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modification of the Catalytic Function of Human Hydroxysteroid Sulfotransferase hSULT2A1 by Formation of Disulfide Bonds

Qin¹,

Teesch²,

Duffel³

2013

Drug Metab Dispos

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“…Triclosan was purchased from Merck (Darmstadt, Germany). Rabbit anti-human EST antibody (for the Western blot assay) [32] was a gift from Dr David RINGER (American Cancer Society) [21] . The peptide antigen sequence used for generating this antibody is NH 2 -(Glu-Gln-Gln-Met-Lys-Glu-SerThr-Leu-Lys-Phe-Arg-Thr-Glu-ILe) [33] .…”

Section: Methodsmentioning

confidence: 99%

Intratumoral estrogen sulfotransferase induction contributes to the anti-breast cancer effects of the dithiocarbamate derivative TM208

Chen

Song

et al. 2015

Acta Pharmacol Sin

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Aim: Sulfotransferase-catalyzed sulfation is the most important pathway for inactivating estrogens. Thus, activation of estrogen sulfotransferase (EST) may be an alternative approach for the treatment of estrogen-dependent breast cancer. In this study we investigated the involvement of EST in anti-breast cancer effects of the dithiocarbamate derivative TM208 in vitro and in vivo. Methods: The viability of human breast cancer MCF-7 cells was determined using a SBB assay. Nude mice bearing MCF-7 cells were orally administered TM208 (50 and 150 mg·kg -1 ·d -1 ) for 18 days. The xenograft tumors and uteri were collected. The mRNA expression of EST was examined with real-time PCR. EST protein was detected with Western blot, ELISA or immunohistochemical staining assays. A radioactive assay was used to measure the EST activity. Uterotropic bioassay was used to examine the uterine estrogen responses. Results: Treatment with TM208 (10, 15 and 20 µmol/L) concentration-dependently increased EST expression in MCF-7 cells in vitro. Co-treatment with triclosan, an inhibitor of sulfonation, abolished TM208-induced cytotoxicity in MCF-7 cells. TM208 exhibited an apparent anti-estrogenic property: it exerted more potent cytotoxicity in E2-treated MCF-7 cells. In the nude mice bearing MCF-7 cells, TM208 administration time-dependently increased the expression and activity of EST, and blocked the gradual increase of E2 concentration in the xenograft tumors. Furthermore, TM208 administration blocked the estrogens-stimulated uterine enlargement. Tamoxifen, a positive control drug, produced similar effects on the expression and activity of EST in vitro and in vivo. Conclusion: The induction of EST and reduction of estrogen concentration contribute to the anti-breast cancer action of TM208 and tamoxifen. TM208 may be developed as anticancer drug for the treatment of estrogen receptor-positive breast cancer.

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“…Although this was first described for purified rSULT1A1 (Marshall et al, 1997), investigations of cytosolic and purified preparations of human estrogen sulfotransferase, hSULT1E1, have indicated that the catalytic function of this SULT also can be altered by treatment with GSSG (Maiti et al, 2007). In addition, studies with rats continuously exposed to hyperoxic condi- tions (i.e., Ͼ95% oxygen) showed that there was an increase in the rate of sulfation of 2-naphthol catalyzed by subsequently isolated hepatic and lung cytosolic fractions (Maiti et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Oxidative Modification of Rat Sulfotransferase 1A1 Activity in Hepatic Tissue Slices Correlates with Effects on the Purified Enzyme

Dammanahalli¹,

Duffel²

2011

Drug Metab Dispos

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ABSTRACT:Mammalian cytosolic sulfotransferases (SULTs) catalyze the sulfation of xenobiotics as well as numerous endogenous molecules. The major aryl (phenol) SULT in rat liver, rSULT1A1, has been used extensively as a model enzyme for understanding the catalytic function of SULTs. Previous studies showed that purified rSULT1A1 displays significant catalytic changes in the presence of GSSG and other oxidants. In the present study, the effects of diamide [1,1-azobis(N,N-dimethylformamide)] and tert-butyl hydroperoxide (TBHP) on the activity of rSULT1A1 in rat hepatic slices were compared with the effects of these oxidants on a homogeneous preparation of the enzyme. Precision-cut hepatic slices were incubated with 10 M 7-hydroxycoumarin (7-HC) in the presence of varied concentrations of either diamide or TBHP. Analysis of the 7-hydroxycoumarin sulfate released into the incubation medium indicated that both oxidants significantly increased the sulfation of 7-HC, and this occurred at optimal concentrations of 5 and 10 M, respectively. Cellular GSH and GSSG levels in the hepatic slices were not significantly altered from control values at these concentrations of diamide and TBHP. Exposure of homogeneous rSULT1A1 to diamide or TBHP also increased the rate of sulfation of 7-HC, although the optimal concentrations of diamide and TBHP were lower (50-and 100-fold, respectively) than those required for effects with the hepatic slices. These results indicate that both diamide and TBHP may modify the rSULT1A1 in intact cells in a manner similar to that observed with the homogeneous purified enzyme.

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Redox regulation of human estrogen sulfotransferase (hSULT1E1)

Cited by 31 publications

References 38 publications

Modification of the Catalytic Function of Human Hydroxysteroid Sulfotransferase hSULT2A1 by Formation of Disulfide Bonds

Modification of the Catalytic Function of Human Hydroxysteroid Sulfotransferase hSULT2A1 by Formation of Disulfide Bonds

Intratumoral estrogen sulfotransferase induction contributes to the anti-breast cancer effects of the dithiocarbamate derivative TM208

Oxidative Modification of Rat Sulfotransferase 1A1 Activity in Hepatic Tissue Slices Correlates with Effects on the Purified Enzyme

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