| one publication added to basket [110877] | Sulfonation of 17ß-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus
Wang, L.-Q.; James, M.O. (2007). Sulfonation of 17ß-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus. Aquat. Toxicol. 81(3): 286-292. https://dx.doi.org/10.1016/j.aquatox.2006.12.011
In: Aquatic Toxicology. Elsevier Science: Tokyo; New York; London; Amsterdam. ISSN 0166-445X; e-ISSN 1879-1514, more
|  |
| Keyword |
|
| Author keywords |
sulfotransferase; sulfonation; channel catfish; inhibition; OH-PCBs;celecoxib |
| Abstract |
The sulfonation of 17β-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 μM, 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 Vmax values of 0.40 ± 0.10 μM and 91.0 ± 4.7 pmol/min/mg protein, respectively and KI of 1.08 ± 0.09μM. The formation of E2-17-S fit Michaelis-Menten kinetics over the concentration range 25nM to 2.5μM, with Km and Vmax values of 1.07 ± 0.23μM and 25.7 ± 4.43 pmol/min/mg protein, respectively. The efficiency (Vmax/Km) 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 1nM. Of those tested, the most potent inhibitor was 4′-OH-CB79, with two chlorine atoms flanking the OH group (IC50: 94nM). 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 (IC50: 44μM) and to a lesser extent, E2-17-S (IC50: >160μM), suggesting the previously found effect of celecoxib on E2-17-S formation may be specific to human SULT2A1. |
|
