Abstract
Cytosolic sulfotransferases, which mediate activation and detoxification of both endogenous and exogenous compounds, consist of at least five different gene families (ST1 to ST5) in mammals. Several cDNAs corresponding to ST1A forms have been reported, but their functional properties are not well characterized. In addition, only a single form of ST1A sulfotransferase has been reported in each experimental animal species despite the expressions of plural forms in humans. Therefore, enzymatic properties of human ST1A3, ST1A5, rat ST1A1, mouse St1a4, and newly isolated rabbit ST1A8 have been characterized and compared by use of their recombinant proteins to clarify the functional difference between human and experimental animal ST1A forms. From the results using more than 25 phenolic chemicals, all the experimental animal ST1A forms showed substrate specificities similar to human ST1A3 rather than ST1A5. They showed high affinities toward p-nitrophenol and 6-hydroxymelatonin as found in human ST1A3. These forms also showed high activities toward umbelliferone and naringenin, but very low activities toward catecholamines, representative substrates of human ST1A5. Hepatic contents of experimental animal ST1A forms varied (66–250 pmol/mg of cytosolic protein) but showed the same order as observed with human ST1A3 (120 pmol/mg). Hepatic content of human ST1A5 was about 19-fold less than that of ST1A3. Therefore, ST1A forms identified in experimental animal species correspond to human ST1A3 functionally. For chemicals such as troglitazone and 2-amino-4′-hydroxy-1-methyl-6-phenylimidazo[4,5-b]pyridine, clear species differences were detected among the ST1A forms examined.
Footnotes
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Send reprint requests to: Prof. Yasushi Yamazoe, Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki-Aoba, Aoba-ku, Sendai 980-8578, Japan. E-mail: yamazoe{at}mail.cc.tohoku.ac.jp
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This study was supported in part by a grant-in-aid from the Ministry of Education, Science, and Culture and the Ministry of Health and Welfare, Japan, and from the Japan Health Sciences Foundation and Smoking Research Foundation.
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↵2 The GenBank accession no. for the rabbit ST1A8 nucleotide sequence is AB029494.
- Abbreviations used are::
- ST
- cytosolic sulfotransferase
- PAPS
- 3′-phosphoadenosine-5′-phosphosulfate
- His-ST1A
- recombinant ST1A protein that has 17 additional amino acid residues at the N-terminal of ΔHis-ST1A
- p-NP
- p-nitrophenol
- 4′-OH-PhIP, 2-amino-4′-hydroxy-1-methyl-6-phenylimidazo[4,5-b] pyridine
- 3-OH-B[a]P, 3-hydroxybenzo[a]pyrene
- PAGE
- polyacrylamide gel electrophoresis
- PCR
- polymerase chain reaction
- DMSO
- dimethyl sulfoxide
- HIAA
- 5-hydroxyindoleacetic acid
- 6-HM
- 6-hydroxymelatonin
- HMC
- 7-hydroxy-4-methylcoumarin (4-methylumbelliferone)
- DHF
- 5,7-dihydroxyflavanone
- Received July 31, 2000.
- Accepted October 10, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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