Disease relevance of Sult1a1

• A phage genomic clone containing 70% of the 3' AST gene coding sequence was isolated after screening a rat genomic library with an ASTIV cDNA [1].
• In contrast, mRNA fractions isolated from some 2AAF-induced liver tumors or from known chemical carcinogen-derived rat hepatoma cell lines showed losses of both AST IV transcript level and in vitro translation capacity, suggesting that regulation at the transcriptional level may become important at late stages of 2AAF-induced hepatocarcinogenesis [2].
• The sulfotransferase employed in these studies was rat hepatic aryl sulfotransferase (AST) IV (also known as tyrosine-ester sulfotransferase, EC 2.8.2.9), for which a cDNA had been previously cloned and expressed in Escherichia coli and the resulting enzyme purified to homogeneity [3].
• Hence, in DEN-initiated rats, the effects of promoting regimens of 9-OH-2-FAA or 9-oxo-2-FAA, 15 oral doses at 50 and 100 mumol/kg of body weight, were compared to those of 2-FAA at 50 mumol/kg of body weight and of the vehicle on the activity of N-hydroxy(OH)-2-FAA sulfotransferase (ST), an isozyme of AST IV and AST IV expression and distribution [4].
• Rat liver N-hydroxy-2-acetylaminofluorene (N-OH-2AAF) sulfotransferase activity is mediated by aryl sulfotransferase IV (AST IV) and causes the bioactivation of N-OH-2AAF to a highly reactive sulfuric acid ester form putatively capable of inducing liver cancer [5].

High impact information on Sult1a1

• Characterization of a complementary DNA for rat liver aryl sulfotransferase IV and use in evaluating the hepatic gene transcript levels of rats at various stages of 2-acetylaminofluorene-induced hepatocarcinogenesis [2].
• These results indicated that the molecular mechanisms for the 2AAF-mediated down regulation of AST IV expression during 2AAF-induced hepatocarcinogenesis involved alterations in regulation at both translational and transcriptional levels [2].
• The AST IV cDNA clone was obtained by immunochemical screening of a male Sprague-Dawley rat liver cDNA library [2].
• Comparison of the PST-I/AST IV cDNA-deduced amino acid sequence with data from a partial (51%) amino acid sequence analysis of purified AST IV showed complete amino acid homology, confirming the identity of the cDNA and establishing that AST IV was an N-blocked, 291-amino acid protein with a molecular mass of 33,909 daltons [2].
• The AST IV cDNA sequence differed from the PST-I cDNA in two principal ways: the 5' end lacked 18 coding bases, and the 3' end contained a 190-base extention in the untranslated region, including a consensus sequence for signalling polyadenylation [2].

Chemical compound and disease context of Sult1a1

• Induction of rat hepatic aryl sulfotransferase (SULT1A1) gene expression by triamcinolone acetonide: impact on minoxidil-mediated hypotension [6].

Biological context of Sult1a1

• ASTIV spans 3.5 kb and contains eight exons and seven introns [1].
• Affinity labeling of aryl sulfotransferase IV. Identification of a peptide sequence at the binding site for 3'-phosphoadenosine-5'-phosphosulfate [3].
• Nucleotide sequence of a full-length cDNA (PST-1) for aryl sulfotransferase from rat liver [7].
• Moreover, age-related alterations in total phenol sulfotransferase activity and the isozyme pattern paralleled changes in the in vivo elimination kinetics and metabolic fate of acetaminophen [8].
• Because hormones have been implicated in the molecular regulation of the sulfotransferase multigene family, the effects of glucocorticoid and antiglucocorticoid hormones on rat hepatic hydroxysteroid sulfotransferase-a and aryl sulfotransferase IV gene expression were investigated in vivo and in primary rat hepatocyte culture [9].

Anatomical context of Sult1a1

• Isolation of the cDNA for Mx-ST will aid in the investigation of the heterogeneity, the tissue localization, and the characterization of the kinetic properties of this important drug-metabolizing enzyme, with respect to other similar phenol sulfotransferases present in rat liver cytosol [10].
• Food deprivation-induced expression of minoxidil sulfotransferase in the hypothalamus uncovered by microarray analysis [11].
• Using this anti-MST antibody, we have immunohistochemically localized minoxidil sulfotransferase in the liver and anagen hair follicles from rat [12].
• Phenol sulfotransferase activity in rat liver parenchymal cells cultured on collagen gels [13].
• The highest activity of phenol sulfotransferase was observed in the lower colon (almost 6% of the liver activity) and the lowest activity in the duodenum (1%) [14].

Associations of Sult1a1 with chemical compounds

• Phenol sulfotransferase enzymes (SULT1) were studied by measuring activities towards 4-methylphenol and estradiol, hydroxysteroid sulfotransferase (SULT2A) activity was determined towards dehydroepiandrosterone (DHEA) [15].
• Enzyme- and sex-specific differences in the intralobular localizations and distributions of aryl sulfotransferase IV (tyrosine-ester sulfotransferase) and alcohol (hydroxysteroid) sulfotransferase a in rat liver [16].
• ATPDA was a time-dependent irreversible inhibitor of the recombinant AST IV, and this inhibition was prevented by including either PAPS or adenosine 3',5'-diphosphate (PAP) in the incubation of AST IV with ATPDA [3].
• A cDNA encoding minoxidil sulfotransferase (Mx-ST), a rat liver cytosolic sulfotransferase that catalyzes the 3'-phosphoadenosine 5'-phosphosulfate-dependent sulfate conjugation of minoxidil and p-nitrophenol, has been isolated from a lambda gt11 cDNA library constructed from poly(A)+ RNA isolated from female Sprague-Dawley rat liver [10].
• Betamethasone and triamcinolone acetonide significantly increased hepatic aryl sulfotransferase IV mRNA to levels that were approximately 252% and approximately 452% of control, respectively [9].

Other interactions of Sult1a1

• These results indicate that, whereas the overall hepatic concentrations of these enzymes are clearly sex-dependent, the intralobular distributions of AST IV and STa are characteristic of each particular sulfotransferase [16].
• These results suggest that glucocorticoids regulate rat hepatic aryl sulfotransferase IV and hydroxysteroid sulfotransferase-a via classical glucocorticoid receptor-mediated and non-classical mechanisms, respectively [9].
• The observation was consistent with the immunolocalization of estrogen sulfotransferase (PV/PP ratio of 3.4 +/- 1.1) but not hydroxysteroid sulfotransferase (PV/PP ratio of 0.29 +/- 0.21) nor phenol sulfotransferase (PV/PP ratio of 1.13 +/- 0.23) [17].
• No consistent diet-related changes were detected in the activities of aryl sulfotransferase or N-acetyltransferase, but UDP-glucuronosyltransferase activities were elevated 2- to 3-fold in rats given chow versus AIN diets [18].
• The phenol-preferring sulfotransferases aryl sulfotransferase IV and N-hydroxyarylamine sulfotransferase catalyze sulfate conjugation of N-hydroxy-2-acetylaminofluorene, a metabolite capable of causing hepatocarcinogenesis in rats [19].

Analytical, diagnostic and therapeutic context of Sult1a1

• The remaining 5' sequence was determined from a PCR product obtained from rat genomic DNA and ASTIV cDNA-specific primers [1].
• Sequence analysis of the AST IV cDNA showed it to be 1127 residues in length and to have essentially complete homology with PST-I cDNA, a previously reported (S. Ozawa, et al., Nucleic Acids Res., 18: 4001, 1990), 1028-base cDNA for an uncharacterized rat liver aryl sulfotransferase [2].
• At approximately 8 months after treatment with the C-9-oxidized compounds at doses twice that of 2-FAA, the extents of decreases in the hepatic N-OH-2-FAA ST activity and cytosolic AST IV protein in tumors were comparable to those with 2-FAA [4].
• Six amino acid residues of PST have been chosen for mutagenesis studies on the basis of a model of PST and its sequence alignment with those of available cytosolic and membrane-anchored STs [20].
• Northern blot analysis indicated that minoxidil sulfotransferase mRNA is up-regulated in the fasted rat and mouse, ob/ob mouse, and fa/fa rat [11].

References