Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus.

Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus. Research Abstract Details 

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Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus. Abstract Text:

Li-Quan Wang,Margaret O James,

The sulfonation of 17beta-estradiol (E2) by human liver and recombinant sulfotransferases is influenced by environmental contaminants such as hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs), which are potent inhibitors, and the therapeutic drug, celecoxib, which affects positional sulfonation of E2. In some locations, the aquatic environment is contaminated by PCBs, OH-PCBs and widely used therapeutic drugs. The objectives of this study were to investigate the sulfonation kinetics of E2 in liver cytosol from channel catfish (Ictalurus punctatus); to examine the effect of OH-PCBs on E2 sulfonation; and to determine if celecoxib altered the position of E2 sulfonation, as it does with human liver cytosol. E2 was converted to both 3- and 17-sulfates by catfish liver cytosol. At E2 concentrations below 1 microM, formation of E2-3-sulfate (E2-3-S) predominated, but substrate inhibition was observed at higher concentrations. Rates of E2-3-S formation at different E2 concentrations were fit to a substrate inhibition model, with K'm and V'max values of 0.40 +/- 0.10 microM and 91.0 +/- 4.7 pmol/min/mg protein, respectively and K(i) of 1.08 +/- 0.09 microM. The formation of E2-17-S fit Michaelis-Menten kinetics over the concentration range 25 nM to 2.5 microM, with K(m) and V(max) values of 1.07 +/- 0.23 microM and 25.7 +/- 4.43 pmol/min/mg protein, respectively. The efficiency (V(max)/K(m)) of formation of E2-3-S was 9.8-fold higher than that of E2-17-S. Several OH-PCBs inhibited E2 3-sulfonation, measured at an E2 concentration of 1 nM. Of those tested, the most potent inhibitor was 4'-OH-CB79, with two chlorine atoms flanking the OH group (IC(50): 94 nM). The inhibition of estrogen sulfonation by OH-PCBs may disrupt the endocrine system and thus contribute to the known toxic effects of these compounds. Celecoxib did not stimulate E2-17-S formation, as is the case with human liver cytosol, but did inhibit the formation of E2-3-S (IC(50): 44 microM) and to a lesser extent, E2-17-S (IC(50): > 160 microM), suggesting the previously found effect of celecoxib on E2-17-S formation may be specific to human SULT2A1.

Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus. Publishing Authors By Initials

LQ Wang,MO James,

For similar enzymes and coenzymes: enzymes: transferases: sulfur group transferases: sulfotransferases research abstracts see: enzymes and coenzymes: enzymes: transferases: sulfur group transferases: sulfotransferases research

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Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Aquatic toxicology (Amsterdam, Netherlands)

VOLUME: 81

Page Numbers: 286-92

Journal Abbreviation: Aquat. Toxicol.

ISSN: 0166-445X

DAY: 3

MONTH: 01

YEAR: 2007

Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8500246

Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus. Keywords Mesh Terms:

KEYWORDS: Sulfotransferases

MESH TERMS: drug effects

Chemical & Substance for Abstract: Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus. Information

Substance Name: Sulfotransferases

Registry Number: EC 2.8.2.-

Grant and Affiliation Information for Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus.

AFFILIATION: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.

Country: Netherlands

AGENCY: United States NIEHS

GRANT: P42 ES013661-01A1

ACRONYM: ES

MEDLINETA: Aquat Toxicol

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