Identification and localization of soluble sulfotransferases in the human gastrointestinal tract.

Soluble SULTs (sulfotransferases) are important in the regulation of messenger molecules and the elimination of xenobiotics. However, sulfo-conjugation of various substrates can also lead to the formation of reactive metabolites that may induce cancer and cause other damage. The aim of the present study was to identify the SULT forms expressed in the human gastrointestinal tract, especially the colon and rectum (common sites for cancer), and to determine their cellular localization. Normal colonic or rectal tissue, resected with tumours, was obtained from 39 subjects. For comparison, we additionally studied one to four samples from stomach, jejunum, ileum, cecum and liver. SULTs were detected by immunoblotting, immunohistochemistry and measurement of enzyme activities. SULT1A1, 1A3 and 1B1 were found in all parts of the gastrointestinal tract, often exceeding levels in liver (where these forms were present at high, undetectable and low levels respectively). They were predominantly localized in differentiated enterocytes. SULT1E1 and 2A1 were only detected in liver, jejunum, ileum and cecum. SULT1C1 was readily found in stomach, but was negligible elsewhere. SULT1A2 was present at low levels in individual samples. The remaining forms were not detected with the limitation that only high levels could be recognized with the antisera used. In conclusion, SULTs are abundant in the gastrointestinal tract of man. We suspect that they are involved in the presystemic elimination of bioactive food-borne components, including aglycones released by gut microbiota, as well as the bioactivation of some procarcinogens.

[1]  R. Hume,et al.  Expression profiling of human fetal cytosolic sulfotransferases involved in steroid and thyroid hormone metabolism and in detoxification , 2005, Molecular and Cellular Endocrinology.

[2]  H. Glatt,et al.  Association between functional genetic polymorphisms of human sulfotransferases 1A1 and 1A2. , 2000, Pharmacogenetics.

[3]  H. Glatt,et al.  Stable expression of rat sulfotransferase 1B1 in V79 cells: activation of benzylic alcohols to mutagens. , 2002, Carcinogenesis.

[4]  T. Nakayama,et al.  Molecular Cloning, Expression, and Characterization of Novel Human SULT1C Sulfotransferases That Catalyze the Sulfonation ofN-Hydroxy-2-acetylaminofluorene* , 1998, The Journal of Biological Chemistry.

[5]  J. Pagliaro,et al.  Specific skin lesions occurring in a patient with Hodgkin’s lymphoma , 1999, The Australasian journal of dermatology.

[6]  M. Hongo,et al.  Expression and activity of dehydroepiandrosterone sulfotransferase in human gastric mucosa , 2000, The Journal of Steroid Biochemistry and Molecular Biology.

[7]  R. Weinshilboum,et al.  A proposed nomenclature system for the cytosolic sulfotransferase (SULT) superfamily. , 2004, Pharmacogenetics.

[8]  C. Falany,et al.  Different subcellular localization of sulphotransferase 2B1b in human placenta and prostate. , 2004, The Biochemical journal.

[9]  C. Falany,et al.  Steroid sulfation by expressed human cytosolic sulfotransferases , 1994, The Journal of Steroid Biochemistry and Molecular Biology.

[10]  R. Weinshilboum,et al.  Human sulfotransferases SULT1C1 and SULT1C2: cDNA characterization, gene cloning, and chromosomal localization. , 2000, Genomics.

[11]  G. Pacifici.  Inhibition of human liver and duodenum sulfotransferases by drugs and dietary chemicals: a review of the literature. , 2004, International journal of clinical pharmacology and therapeutics.

[12]  D. Goldstein,et al.  Dopamine sulphate: an enigma resolved. , 1999, Clinical and experimental pharmacology & physiology. Supplement.

[13]  K. Audus,et al.  Substrate specificity of phenol sulfotransferase from primary cultures of bovine brain microvessel endothelium , 1989, Neurochemical Research.

[14]  R. Weinshilboum,et al.  Phenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype. , 1997, Biochemical and biophysical research communications.

[15]  H. Glatt,et al.  Human fetal adrenal hydroxysteroid sulphotransferase: cDNA cloning, stable expression in V79 cells and functional characterisation of the expressed enzyme , 1995, Molecular and Cellular Endocrinology.

[16]  H. Glatt,et al.  Human sulphotransferases are involved in the activation of aristolochic acids and are expressed in renal target tissue , 2006, International journal of cancer.

[17]  C. Falany,et al.  Expression and characterization of a novel thyroid hormone-sulfating form of cytosolic sulfotransferase from human liver. , 1998, Molecular pharmacology.

[18]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[19]  H. Glatt.  Activation and Inactivation of Carcinogens and Mutagens by Human Sulfotransferases , 2005 .

[20]  R. Weinshilboum,et al.  Human jejunal estrogen sulfotransferase and dehydroepiandrosterone sulfotransferase: immunochemical characterization of individual variation. , 1996, Drug metabolism and disposition: the biological fate of chemicals.

[21]  T. Visser,et al.  Pathways of thyroid hormone metabolism. , 1996, Acta medica Austriaca.

[22]  B. Green,et al.  Examination of Human Tissue Cytosols for Expression of Sulfotransferase Isoform 1A2 (SULT1A2) Using a SULT1A2-Specific Antibody , 2005, Molecular Pharmacology.

[23]  R. Weinshilboum,et al.  Human sulfotransferase SULT1C1: cDNA cloning, tissue-specific expression, and chromosomal localization. , 1997, Genomics.

[24]  R. Weinshilboum,et al.  Human intestinal phenol sulfotransferase: assay conditions, activity levels and partial purification of the thermolabile form. , 1989, Drug metabolism and disposition: the biological fate of chemicals.

[25]  C. Falany.  Enzymology of human cytosolic sulfotransferases , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[26]  Susan Holmes.  Nutrition and the prevention of cancer. , 2006, The journal of family health care.

[27]  C. Falany,et al.  Molecular cloning and expression of novel sulphotransferase-like cDNAs from human and rat brain. , 2000, The Biochemical journal.

[28]  R. Weinshilboum,et al.  Human liver dehydroepiandrosterone sulfotransferase: Nature and extent of individual variation , 1993, Clinical pharmacology and therapeutics.

[29]  C. Klaassen,et al.  Tissue-specific expression of rat sulfotransferase messenger RNAs. , 1998, Drug metabolism and disposition: the biological fate of chemicals.

[30]  M. Manns,et al.  UDP-glucuronosyltransferase activity in human liver and colon. , 1999, Gastroenterology.

[31]  C. Strott.  Sulfonation and molecular action. , 2002, Endocrine reviews.

[32]  R. Waring,et al.  Activity of phenolsulfotransferases in the human gastrointestinal tract. , 2000, Life sciences.

[33]  C. Falany,et al.  Expression and characterization of the human 3β-hydroxysteroid sulfotransferases (SULT2B1a and SULT2B1b) , 2001, The Journal of Steroid Biochemistry and Molecular Biology.

[34]  R. Weinshilboum,et al.  Human cytosolic sulfotransferase database mining: identification of seven novel genes and pseudogenes , 2004, The Pharmacogenomics Journal.

[35]  R. Haldeman-Cahill,et al.  Expression profiling of human sulfotransferase and sulfatase gene superfamilies in epithelial tissues and cultured cells. , 2000, Biochemical and biophysical research communications.

[36]  C. Falany,et al.  Bacterial expression and kinetic characterization of the human monoamine-sulfating form of phenol sulfotransferase. , 1995, Drug metabolism and disposition: the biological fate of chemicals.

[37]  C. Falany,et al.  Human gastrointestinal sulfotransferases: identification and distribution. , 2003, Toxicology and applied pharmacology.

[38]  K. A. Comer,et al.  Immunological characterization of dehydroepiandrosterone sulfotransferase from human liver and adrenal. , 1992, Molecular pharmacology.

[39]  A. Li,et al.  Estrogen sulfotransferase expression in the human liver: marked interindividual variation and lack of gender specificity. , 1998, The Journal of pharmacology and experimental therapeutics.

[40]  J. Miller,et al.  Sulfonation in Chemical Carcinogenesis , 1994 .

[41]  M. McManus,et al.  Localisation of aryl sulfotransferase expression in human tissues using hybridisation histochemistry and immunohistochemistry. , 1998, Chemico-biological interactions.

[42]  M. Shimada,et al.  Enzymatic characterization of human cytosolic sulfotransferases; identification of ST1B2 as a thyroid hormone sulfotransferase. , 1999, Biological & pharmaceutical bulletin.