Expression Profiling of Human Sulfotransferase and Sulfatase Gene Superfamilies in Epithelial Tissues and Cultured Cells

Dooley, Thomas P.; Haldeman-Cahill, Ruth; Joiner, Julie; Wilborn, Teresa W.

doi:10.1006/bbrc.2000.3905

Cited by 47 publications

(76 citation statements)

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“…6). This finding is in accord with previous reports on the high level of expression of SULT1A3 in the small intestine (43,44,47). It is to be noted that previous studies had also demonstrated the sulfation of salbutamol in the human lung, liver and intestine (48 50).…”

Section: Discussionsupporting

confidence: 92%

“…Another important issue is related to the tissues/organs capable of metabolizing ractopamine and salbutamol through sulfation. SULT1A3 is known to be expressed in many organs including the brain, lung, liver, kidney and gastrointestinal tract (43,44). Since residual ractopamine and salbutamol, on dietary meat consumption, may enter the body through the gastrointestinal Sulfation of ractopamine and salbutamol tract, these compounds may first be subjected to the sulfate conjugation in the intestine.…”

Section: Discussionmentioning

confidence: 99%

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Sulfation of ractopamine and salbutamol by the human cytosolic sulfotransferases

Kurogi

Davidson

et al. 2012

Journal of Biochemistry

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-Cheh Liu *These two authors contributed equally to this study.Feed additives such as ractopamine and salbutamol are pharmacologically active compounds, acting primarily as b-adrenergic agonists. This study was designed to investigate whether the sulfation of ractopamine and salbutamol may occur under the metabolic conditions and to identify the human cytosolic sulfotransferases (SULTs) that are capable of sulfating two major feed additive compounds, ractopamine and salbutamol. A metabolic labelling study showed the generation and release of [ 35 S]sulfated ractopamine and salbutamol by HepG2 human hepatoma cells labelled with [ 35 S]sulfate in the presence of these two compounds. A systematic analysis using 11 purified human SULTs revealed SULT1A3 as the major SULT responsible for the sulfation of ractopamine and salbutamol. The pH dependence and kinetic parameters were analyzed. Moreover, the inhibitory effects of ractopamine and salbutamol on SULT1A3-mediated dopamine sulfation were investigated. Cytosol or S9 fractions of human lung, liver, kidney and small intestine were examined to verify the presence of ractopamine-/ salbutamol-sulfating activity in vivo. Of the four human organs, the small intestine displayed the highest activity towards both compounds. Collectively, these results imply that the sulfation mediated by SULT1A3 may play an important role in the metabolism and detoxification of ractopamine and salbutamol.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Sulfation of ractopamine and salbutamol by the human cytosolic sulfotransferases

Kurogi

Davidson

et al. 2012

Journal of Biochemistry

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“…11,13,27,28 Various sulfotransferases, including SULT1A1 and SULT1A3, were detected by RT-PCR in tissue and oral carcinoma lines. 29 Expression of MGST1 was shown in oral fibroblasts but not reported for keratinocytes. 30 To the best of our knowledge, presence of UGT2B, GSTT1 and CAT transcripts was not previously reported for oral keratinocytes.…”

Section: Discussionmentioning

confidence: 95%

Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and simian virus 40 T antigen‐immortalized oral keratinocytes

Vondracek

Weaver

Sarang

et al. 2002

Intl Journal of Cancer

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The metabolic detoxification capacity may critically regulate the susceptibility of human tissues to cancer development. We used standardized and quantitative, reverse transcription-polymerase chain reaction (StaRT-PCR) and microarray chip techniques to analyze transcript levels of multiple detoxification enzymes in cultured normal human oral keratinocytes (NOK) and the Siman virus 40 T antigenimmortalized oral keratinocyte line SVpgC2a, viewing the latter as a model of a benign tumor state. With good agreement between the 2 methodologies, NOK and SVpgC2a were found to express transcripts for cytochrome P450 enzymes (CYPs), factors related to CYP induction and enzymes involved in conjugation reactions or detoxification of reactive oxygen. The cell types expressed similar levels of CYP 2B6/7, CYP 2E1, P450 oxidoreductase, the aryl hydrocarbon receptor nuclear translocator, sulfotransferase 1A1, sulfotransferase 1A3, epoxide hydrolase, glutathione S-transferase M3, glutathione S-transferase pi and catalase, superoxide dismutase 1, glutathione peroxidase 1 and glutathione peroxidase 3. In contrast, SVpgC2a exhibited comparatively higher levels of CYP1A1, 1B1, aryl hydrocarbon receptor, glutathione S-transferase M1, 2, 4, 5, glutathione S-transferase theta 1 and superoxide dismutase 2 and comparatively lower levels of UDP glycosyltransferase 2 and microsomal glutathione S-transferase 1. Some transcripts, e.g., CYP 2A6/7, were not detected by either standard, non quantitative RT-PCR or the above methods, whereas others were barely quantifiable by StaRT-PCR, i.e., were present at 1-10 molecules/10 6 molecules of actin. Overall, the expression analysis demonstrated presence of mRNA for multiple enzymes involved in foreign compound metabolism and detoxification pathways, including several enzymes not previously reported for oral epithelium. Generally, the comparison of NOK from 2 individuals indicated relatively similar transcript levels of these enzymes. In contrast, differences between NOK and SVpgC2a, e.g., for CYP1B1, may reflect alteration caused by immortalization and aid identification of early stage tumor markers in oral epithelium. © 2002 Wiley-Liss, Inc. Key words: oral epithelium; biotransformation; phase I and II metabolizing enzymes; mRNA expressionSeveral enzyme systems including cytochrome P450s (CYPs), conjugation enzymes and enzymes involved in detoxification of reactive oxygen species (ROS) cooperate to protect the organism against reactive agents that are potentially carcinogenic and stress inducing. 1 Oxidative metabolism (so called phase I metabolism), carried out by the CYP family of enzymes, initiate biotransformation of compounds, which do not possess functional groups suitable for conjugation and can thereby generate toxic and mutagenic/ carcinogenic intermediates. 2 Following CYP dependent oxidative activation, conjugation enzymes (involved in so called phase II metabolism) including transferases for glutathione, sulfate, acetyl moieties and glucuronic acid generally decrease the reactivity of ...

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“…In contrast, EST is known to consist of a number of isoenzyme forms. 58 Dooley and colleagues 59 recently reported that estrogen sulfotransferase gene (1E1) transcripts are present in various human normal tissues. Results of a recent study using mRNA analysis, immunohistochemistry, and activity demonstrated that EST was present in a wide range of human tissues.…”

Section: Discussionmentioning

confidence: 99%

Steroid Sulfatase and Estrogen Sulfotransferase in the Atherosclerotic Human Aorta

Nakamura

Miki

Suzuki

et al. 2003

The American Journal of Pathology

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Various epidemiological studies have demonstrated a relatively low incidence of cardiovascular events in premenopausal women and its marked increment after menopause. In addition, estrogens have been postulated to exert direct anti-atherogenic effects via binding to estrogen receptors in vascular smooth muscle cells (VSMCs). However, not all postmenopausal women develop atherosclerosis despite decreased levels of serum estrogen. Therefore, we believe it is important to examine the status of estrogen metabolism in situ in the human cardiovascular system. Estrone sulfate (E1S) is a major circulating plasma estrogen that is converted into the biologically active estrogen, estrone (E1) by steroid sulfatase (STS). E1 is also sulfated and reverted into E1S by estrogen sulfotransferase (EST). These two enzymes have recently been shown to play important roles in the in situ estrogen actions of estrogen-dependent human tissues and various sex steroid-dependent tumors. STS and EST, however, have not been studied in detail in the human vascular system associated with atherosclerotic changes. In the present study, we evaluated the relative abundance of STS-and ESTimmunoreactive protein and mRNA expression in human aorta using immunohistochemistry and reverse transcription followed by quantitative polymerase chain reaction in addition to enzyme activity. STS expression levels were found to be significantly higher in the VSMCs obtained from female aortas with mild atherosclerotic changes than in those with severe atherosclerotic changes and in male aortas regardless of atherosclerotic changes. EST expression levels in the VSMCs of these aortas, however, were significantly higher in female aortas with severe atherosclerotic changes and in male aortas than in female aortas with mild atherosclerotic changes. We believe it is important to examine factors regulating the expression and activity of these estrogen-metabolizing enzymes in the human aorta. Various cytokines have been proposed to function as regulators of these enzymes in other tissues. In the present study, we studied the effects of interleukin (IL)-1␤, known to be produced in human atherosclerotic lesions, on the expression of these enzymes using cultured human VSMCs originally obtained from a female patient. IL-1␤ markedly inhibited the expression of STS mRNA and enzyme activity, but stimulated the expression of EST mRNA and enzyme activity. In addition, IL-1␤ also reduced E2 production from E1S and E1 in VSMCs.Results from the present study seem to suggest that the expression levels of both STS and EST mRNA and activity may be significantly associated with the degree of atherosclerotic changes in the female aorta, which may be related to cytokines produced in situ, such as IL-1␤, in human atherosclerotic lesions. Various epidemiological studies have reported a relatively low incidence of cardiovascular events in premenopausal women and its marked increment after menopause.1 Estrogen has, therefore, been proposed as a cardioprotective agent, especially in women.2 In ...

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Expression Profiling of Human Sulfotransferase and Sulfatase Gene Superfamilies in Epithelial Tissues and Cultured Cells

Cited by 47 publications

References 0 publications

Sulfation of ractopamine and salbutamol by the human cytosolic sulfotransferases

Sulfation of ractopamine and salbutamol by the human cytosolic sulfotransferases

Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and simian virus 40 T antigen‐immortalized oral keratinocytes

Steroid Sulfatase and Estrogen Sulfotransferase in the Atherosclerotic Human Aorta

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