کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2582147 1130223 2006 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Polychlorobiphenylols are selective inhibitors of human phenol sulfotransferase 1A1 with 4-nitrophenol as a substrate
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Polychlorobiphenylols are selective inhibitors of human phenol sulfotransferase 1A1 with 4-nitrophenol as a substrate
چکیده انگلیسی
Polychlorobiphenylols (OH-PCBs) were reported as potent inhibitors of estrogen sulfotransferase, thyroid hormone and 3-hydroxybenzo(a)pyrene sulfotransferases. The aim of this study was to examine the effects of selected OH-PCBs on SULT1A1 activity in human liver cytosol, measured with 4 μM 4-nitrophenol, a concentration considered to be diagnostic for selectively detecting SULT1A1. All the OH-PCBs studied inhibited the sulfonation of 4-nitrophenol in human liver cytosol. Among the eighteen OH-PCBs studied, 3′-OH-CB3 (4-chlorobiphenyl-3′-ol) was the most potent inhibitor (IC50: 0.73 ± 0.15 μM, mean ± S.D., n = 3). The least potent inhibitor studied was 6′-OH-CB35 (3,3′,4-trichlorobiphenyl-6′-ol) with IC50: 49.1 ± 10.8 μM. The IC50 values of the other OH-PCBs studied ranged from 0.78 to 3.76 μM. Some OH-PCBs with various inhibitory potencies with human liver cytosol were selected for study with recombinant human SULT1A1 and SULT1B1. These OH-PCBs showed more potent inhibition of 4-nitrophenol sulfonation with SULT1A1 than with human liver cytosol. The IC50 values with human liver cytosol showed a perfect linear correlation with those found with SULT1A1 (r2 = 1), but not with SULT1B1 (r2 = 0.21). The results suggested that in these human samples SULT1A1 was predominantly responsible for the sulfonation of 4-nitrophenol, with very little or no contribution from SULT1B1. The kinetics of inhibition were studied with 4′-OH-CB165, which is similar in structure to OH-PCBs found in human blood. The 4′-OH-CB165 was a mixed noncompetitive-uncompetitive inhibitor (Ki = 1.80 ± 0.2 μM, Kies = 0.16 ± 0.02 μM). Finally, it was demonstrated that the tested OH-PCBs were themselves only slowly sulfonated by human sulfotransferases in the presence of 35S-PAPS, as measured by the production of 35S-labeled metabolites. Although this series of 18 OH-PCBs was too small to draw conclusions about structure-potency relationships, this work demonstrated that several OH-PCBs were potent inhibitors of 4-nitrophenol sulfonation but poor substrates in human liver cytosol, and suggested that OH-PCBs may inhibit the sulfation rate of those xenobiotics sulfated by SULT1A1.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 159, Issue 3, 25 February 2006, Pages 235-246
نویسندگان
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