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
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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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, 3â²-OH-CB3 (4-chlorobiphenyl-3â²-ol) was the most potent inhibitor (IC50: 0.73 ± 0.15 μM, mean ± S.D., n = 3). The least potent inhibitor studied was 6â²-OH-CB35 (3,3â²,4-trichlorobiphenyl-6â²-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 4â²-OH-CB165, which is similar in structure to OH-PCBs found in human blood. The 4â²-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
Journal: Chemico-Biological Interactions - Volume 159, Issue 3, 25 February 2006, Pages 235-246
نویسندگان
Li-Quan Wang, Hans-Joachim Lehmler, Larry W. Robertson, Margaret O. James,