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Title: Arsenite enhances tumor necrosis factor-{alpha}-induced expression of vascular cell adhesion molecule-1

Abstract

Epidemiological studies demonstrated a high association of vascular diseases with arsenite exposure. We hypothesize that arsenite potentiates the effect of proinflammatory cytokines on vascular endothelial cells, and hence contributes to atherosclerosis. In this study, we investigated the effect of arsenite and its induction of glutathione (GSH) on vascular cell adhesion molecule-1 (VCAM-1) protein expression in human umbilical vein endothelial cells (HUVECs) in response to tumor necrosis factor-{alpha} (TNF-{alpha}), a typical proinflammatory cytokine. Our study demonstrated that arsenite pretreatment potentiated the TNF-{alpha}-induced VCAM-1 expression with up-regulations of both activator protein-1 (AP-1) and nuclear factor-{kappa}B (NF-{kappa}B). To elucidate the role of GSH in regulation of AP-1, NF-{kappa}B, and VCAM-1 expression, we employed L-buthionine (S,R)-sulfoximine (BSO), a specific {gamma}-glutamylcysteine synthetase ({gamma}-GCS) inhibitor, to block intracellular GSH synthesis. Our investigation revealed that, by depleting GSH, arsenite attenuated the TNF-{alpha}-induced VCAM-1 expression as well as a potentiation of AP-1 and an attenuation of NF-{kappa}B activations by TNF-{alpha}. Moreover, we found that depletion of GSH would also attenuate the TNF-{alpha}-induced VCAM-1 expression with a down-regulation of the TNF-{alpha}-induced NF-{kappa}B activation and without significant effect on AP-1. On the other hand, the TNF-{alpha}-induced VCAM-1 expression could be completely abolished by inhibition of AP-1 or NF-{kappa}B activity, suggestingmore » that activation of both AP-1 and NF-{kappa}B was necessary for VCAM-1 expression. In summary, we demonstrate that arsenite enhances the TNF-{alpha}-induced VCAM-1 expression in HUVECs via regulation of AP-1 and NF-{kappa}B activities in a GSH-sensitive manner. Our present study suggested a potential mechanism for arsenite in the induction of vascular inflammation and vascular diseases via modulating the actions of proinflammatory cytokines.« less

Authors:
 [1];  [2];  [3];  [4];  [2];  [5];  [2]
  1. Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan (China). E-mail: tctsou@nhri.org.tw
  2. Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan (China)
  3. Department of Obstetrics and Gynecology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China)
  4. (China)
  5. Department of Environmental and Safety Health Engineering, Chung Hwa College of Medical Technology, Tainan, Taiwan (China)
Publication Date:
OSTI Identifier:
20783366
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 209; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2005.03.006; PII: S0041-008X(05)00131-6; Copyright (c) 2005 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; ARTERIOSCLEROSIS; GENE REGULATION; GLUTATHIONE; INFLAMMATION; LIGASES; LYMPHOKINES; VEINS

Citation Formats

Tsou, T.-C., Yeh, Szu Ching, Tsai, E.-M., Department of Obstetrics and Gynecology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan, Tsai, F.-Y., Chao, H.-R., and Chang, Louis W. Arsenite enhances tumor necrosis factor-{alpha}-induced expression of vascular cell adhesion molecule-1. United States: N. p., 2005. Web. doi:10.1016/j.taap.2005.03.006.
Tsou, T.-C., Yeh, Szu Ching, Tsai, E.-M., Department of Obstetrics and Gynecology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan, Tsai, F.-Y., Chao, H.-R., & Chang, Louis W. Arsenite enhances tumor necrosis factor-{alpha}-induced expression of vascular cell adhesion molecule-1. United States. doi:10.1016/j.taap.2005.03.006.
Tsou, T.-C., Yeh, Szu Ching, Tsai, E.-M., Department of Obstetrics and Gynecology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan, Tsai, F.-Y., Chao, H.-R., and Chang, Louis W. Tue . "Arsenite enhances tumor necrosis factor-{alpha}-induced expression of vascular cell adhesion molecule-1". United States. doi:10.1016/j.taap.2005.03.006.
@article{osti_20783366,
title = {Arsenite enhances tumor necrosis factor-{alpha}-induced expression of vascular cell adhesion molecule-1},
author = {Tsou, T.-C. and Yeh, Szu Ching and Tsai, E.-M. and Department of Obstetrics and Gynecology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan and Tsai, F.-Y. and Chao, H.-R. and Chang, Louis W.},
abstractNote = {Epidemiological studies demonstrated a high association of vascular diseases with arsenite exposure. We hypothesize that arsenite potentiates the effect of proinflammatory cytokines on vascular endothelial cells, and hence contributes to atherosclerosis. In this study, we investigated the effect of arsenite and its induction of glutathione (GSH) on vascular cell adhesion molecule-1 (VCAM-1) protein expression in human umbilical vein endothelial cells (HUVECs) in response to tumor necrosis factor-{alpha} (TNF-{alpha}), a typical proinflammatory cytokine. Our study demonstrated that arsenite pretreatment potentiated the TNF-{alpha}-induced VCAM-1 expression with up-regulations of both activator protein-1 (AP-1) and nuclear factor-{kappa}B (NF-{kappa}B). To elucidate the role of GSH in regulation of AP-1, NF-{kappa}B, and VCAM-1 expression, we employed L-buthionine (S,R)-sulfoximine (BSO), a specific {gamma}-glutamylcysteine synthetase ({gamma}-GCS) inhibitor, to block intracellular GSH synthesis. Our investigation revealed that, by depleting GSH, arsenite attenuated the TNF-{alpha}-induced VCAM-1 expression as well as a potentiation of AP-1 and an attenuation of NF-{kappa}B activations by TNF-{alpha}. Moreover, we found that depletion of GSH would also attenuate the TNF-{alpha}-induced VCAM-1 expression with a down-regulation of the TNF-{alpha}-induced NF-{kappa}B activation and without significant effect on AP-1. On the other hand, the TNF-{alpha}-induced VCAM-1 expression could be completely abolished by inhibition of AP-1 or NF-{kappa}B activity, suggesting that activation of both AP-1 and NF-{kappa}B was necessary for VCAM-1 expression. In summary, we demonstrate that arsenite enhances the TNF-{alpha}-induced VCAM-1 expression in HUVECs via regulation of AP-1 and NF-{kappa}B activities in a GSH-sensitive manner. Our present study suggested a potential mechanism for arsenite in the induction of vascular inflammation and vascular diseases via modulating the actions of proinflammatory cytokines.},
doi = {10.1016/j.taap.2005.03.006},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 209,
place = {United States},
year = {Tue Nov 15 00:00:00 EST 2005},
month = {Tue Nov 15 00:00:00 EST 2005}
}