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Title: Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs

Abstract

The current study was designed to examine the role of sulfation in the metabolism of cigarette smoke toxicants and clarify whether these toxicants, by serving as substrates for the cytosolic sulfotransferases (SULTs), may interfere with the sulfation of key endogenous compounds. By metabolic labeling, [{sup 35}S]sulfated species were found to be generated and released into the media of HepG2 human hepatoma cells and primary human lung endothelial cells labeled with [{sup 35}S]sulfate in the presence of cigarette smoke extract (CSE). Concomitantly, several [{sup 35}S]sulfated metabolites observed in the medium in the absence of CSE either decreased or disappeared. Eleven previously prepared human cytosolic SULTs were tested for sulfating activity with CSE and known cigarette smoke toxicants as substrates. Activity data revealed SULT1A1, SULT1A2, SULT1A3, and SULT1C2 as major enzymes responsible for their sulfation. To examine their inhibitory effects on the sulfation of 17{beta}-estradiol by SULT1A1, enzymatic assays were performed in the presence of three representative toxicant compounds, namely N-hydroxy-4-aminobiphenyl (N-OH-4-ABP), 4-aminobiphenyl (4-ABP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). IC{sub 50} values determined for the sulfation of 17{beta}-estradiol by SULT1A1 were 11.8 {mu}M, 28.2 {mu}M, and 500 {mu}M, respectively, for N-OH-4-ABP, 4-ABP and PhIP. Kinetic analyses indicated that the mechanism underlying the inhibition ofmore » 17{beta}-estradiol sulfation by these cigarette smoke toxicants is of a mixed competitive-noncompetitive type. Metabolic labeling experiments clearly showed inhibition of the production of [{sup 35}S]sulfated 17{beta}-estradiol by N-OH-4-ABP in a concentration-dependent manner in HepG2 cells. Taken together, these results suggest that sulfation plays a significant role in the metabolism of cigarette smoke compounds. By serving as substrates for SULTs, cigarette smoke toxicants may interfere with the metabolism of 17{beta}-estradiol and other endogenous compounds.« less

Authors:
 [1];  [1];  [1];  [2];  [3];  [4]
+ Show Author Affiliations
  1. Biomedical Research Center, University of Texas Health Center, 11937 U.S. Highway 271, Tyler, TX 75708 (United States)
  2. Division of Arts and Sciences, Jarvis Christian College, Hawkins, TX 75765 (United States)
  3. School of Mathematics and Science, J. Sargeant Reynolds Community College, Richmond, VA 23285 (United States)
  4. Biomedical Research Center, University of Texas Health Center, 11937 U.S. Highway 271, Tyler, TX 75708 (United States). E-mail: ming.liu@uthct.edu
Publication Date:
OSTI Identifier:
20976930
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 221; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2007.02.013; PII: S0041-008X(07)00085-3; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ENZYMES; ESTRADIOL; HEPATOMAS; HUMAN POPULATIONS; INHIBITION; LABELLING; LUNGS; METABOLISM; METABOLITES; PYRIDINE; SUBSTRATES; SULFATES; SULFATION; TOBACCO SMOKES

Citation Formats

Yasuda, Shin, Idell, Steven, Fu Jian, Carter, Glendora, Snow, Rhodora, and Liu, M.-C.. Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs. United States: N. p., 2007. Web. doi:10.1016/j.taap.2007.02.013.
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Yasuda, Shin, Idell, Steven, Fu Jian, Carter, Glendora, Snow, Rhodora, & Liu, M.-C.. Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs. United States. doi:10.1016/j.taap.2007.02.013.
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Yasuda, Shin, Idell, Steven, Fu Jian, Carter, Glendora, Snow, Rhodora, and Liu, M.-C.. Tue . "Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs". United States. doi:10.1016/j.taap.2007.02.013.
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@article{osti_20976930,
title = {Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs},
author = {Yasuda, Shin and Idell, Steven and Fu Jian and Carter, Glendora and Snow, Rhodora and Liu, M.-C.},
abstractNote = {The current study was designed to examine the role of sulfation in the metabolism of cigarette smoke toxicants and clarify whether these toxicants, by serving as substrates for the cytosolic sulfotransferases (SULTs), may interfere with the sulfation of key endogenous compounds. By metabolic labeling, [{sup 35}S]sulfated species were found to be generated and released into the media of HepG2 human hepatoma cells and primary human lung endothelial cells labeled with [{sup 35}S]sulfate in the presence of cigarette smoke extract (CSE). Concomitantly, several [{sup 35}S]sulfated metabolites observed in the medium in the absence of CSE either decreased or disappeared. Eleven previously prepared human cytosolic SULTs were tested for sulfating activity with CSE and known cigarette smoke toxicants as substrates. Activity data revealed SULT1A1, SULT1A2, SULT1A3, and SULT1C2 as major enzymes responsible for their sulfation. To examine their inhibitory effects on the sulfation of 17{beta}-estradiol by SULT1A1, enzymatic assays were performed in the presence of three representative toxicant compounds, namely N-hydroxy-4-aminobiphenyl (N-OH-4-ABP), 4-aminobiphenyl (4-ABP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). IC{sub 50} values determined for the sulfation of 17{beta}-estradiol by SULT1A1 were 11.8 {mu}M, 28.2 {mu}M, and 500 {mu}M, respectively, for N-OH-4-ABP, 4-ABP and PhIP. Kinetic analyses indicated that the mechanism underlying the inhibition of 17{beta}-estradiol sulfation by these cigarette smoke toxicants is of a mixed competitive-noncompetitive type. Metabolic labeling experiments clearly showed inhibition of the production of [{sup 35}S]sulfated 17{beta}-estradiol by N-OH-4-ABP in a concentration-dependent manner in HepG2 cells. Taken together, these results suggest that sulfation plays a significant role in the metabolism of cigarette smoke compounds. By serving as substrates for SULTs, cigarette smoke toxicants may interfere with the metabolism of 17{beta}-estradiol and other endogenous compounds.},
doi = {10.1016/j.taap.2007.02.013},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 221,
place = {United States},
year = {Tue May 15 00:00:00 EDT 2007},
month = {Tue May 15 00:00:00 EDT 2007}
}
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Journal Article:
DOI:  10.1016/j.taap.2007.02.013
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