Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs

doi:10.1016/j.taap.2007.02.013

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

Full Record
Other Related Research

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 »« less

Authors:

Yasuda, Shin ^[1]; Idell, Steven ^[1]; Fu Jian ^[1]; Carter, Glendora ^[2]; Snow, Rhodora ^[3]; Liu, M.-C. ^[4]

Biomedical Research Center, University of Texas Health Center, 11937 U.S. Highway 271, Tyler, TX 75708 (United States)
Division of Arts and Sciences, Jarvis Christian College, Hawkins, TX 75765 (United States)
School of Mathematics and Science, J. Sargeant Reynolds Community College, Richmond, VA 23285 (United States)
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:: Tue May 15 00:00:00 EDT 2007

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.

Copy to clipboard


                    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.

Copy to clipboard


                    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.

Copy to clipboard


                    
@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}

}

Copy to clipboard

Journal Article:

DOI: 10.1016/j.taap.2007.02.013

Other availability

Find in Google Scholar

Search WorldCat to find libraries that may hold this journal

Save / Share:

Export Metadata

Save to My Library

Similar records in OSTI.GOV collections:

Prenatal cigarette smoke exposure: Pregnancy outcome and gestational changes in plasma nicotine concentration, hematocrit, and carboxyhemoglobin in a newly standardized rat model

Journal Article Farkas, Svetlana ; Hussein, Jabeen ; Ariano, Robert E. ; ... - Toxicology and Applied Pharmacology

Epidemiological studies support an association between perinatal cigarette smoke (CS) exposure and a number of severe pre- and postnatal complications. However, the mechanisms through which CS enhances such risks largely remain unknown. One of the reasons for our inability to discover such mechanisms has been the unavailability of a clinically relevant and physiologically concordant animal model. A number of studies have previously used nicotine (Nic) as surrogate for CS. We sought to (1) establish the amount of CS exposure to achieve plasma Nic concentrations observed among moderate to heavy smokers (20-60 ng/ml) (2) investigate the temporal changes in plasma Nicmore »« less
DOI: 10.1016/j.taap.2005.12.010
Cigarette smoke decreases mitochondrial porin expression and steroidogenesis

Journal Article Bose, Mahuya ; Whittal, Randy M. ; Gairola, C. Gary ; ... - Toxicology and Applied Pharmacology

Steroidogenic acute regulatory protein (StAR) facilitates the movement of cholesterol from the outer to inner mitochondrial membrane for steroidogenesis. Here, we investigated the effect of cigarette smoke (CS) on steroidogenesis using adrenal mitochondria isolated from mice chronically exposed to CS. Steroidogenesis was decreased approximately 78% in CS-exposed mitochondria, as measured by synthesis of the steroid hormone precursor pregnenolone. This effect was accompanied by decreased mitochondrial import of {sup 35}S-StAR. Further characterization of the imported {sup 35}S-StAR by native gradient PAGE revealed the presence of a high molecular weight complex in both control and CS-exposed groups. Following density gradient fractionation ofmore »« less
DOI: 10.1016/j.taap.2007.10.021
Molecular mechanism of reduction in pregnenolone synthesis by cigarette smoke

Journal Article Bose, Mahuya ; Whittal, Randy M. ; Gairola, C. Gary ; ... - Toxicology and Applied Pharmacology

Steroidogenic acute regulatory protein (StAR) facilitates the movement of cholesterol from the outer to inner mitochondrial membrane for the synthesis of pregnenolone. Here, we investigated the molecular mechanism of the reduction of pregnenolone synthesis by cigarette smoke condensate (CSC). Pre-exposure or post-exposure of cells with CSC led to reduced pregnenolone synthesis, in a fashion similar to its effect on isolated mitochondria. However, there was no difference in the expression of 30 kDa StAR in cells treated with moderately concentrated CSC by either regimen. The active form of 37 kDa StAR is degraded easily suggesting that the continuous presence of CSCmore »« less
DOI: 10.1016/j.taap.2008.01.007
Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

Journal Article Yamada, Shigeyuki ; Zhang Xiuquan ; Kadono, Toshie ; ... - Toxicology and Applied Pharmacology

Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca{sup 2+}]{sub i} was measured by flow cytometry using fluo-3. Mitochondrial [Ca{sup 2+}] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified bymore »« less
DOI: 10.1016/j.taap.2009.01.008
Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

Journal Article Han Suxia ; He Guangming ; Wang Tao ; ... - Toxicology and Applied Pharmacology

Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along withmore »« less

Similar Records