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Effect of Arsenic on Transcription Factor AP-1 and NF-kB DNA Binding Activity and Related Gene Expression

Citation

Hu, Y and Jin, X and Snow, ET, Effect of Arsenic on Transcription Factor AP-1 and NF-kB DNA Binding Activity and Related Gene Expression, Toxicology Letters, 133, (1) pp. 33-45. ISSN 0378-4274 (2002) [Refereed Article]

DOI: doi:10.1016/S0378-4274(02)00083-8

Abstract

Both acute (24 h) and chronic (10-20 week) exposure of human fibroblast cells to low dose sodium arsenite (As(III)) significantly affects activating protein-1 (AP-1) and nuclear factor kappa B (NF-κB) DNA binding activity. Short-term treatment with 0.1-5 μM As(III) up-regulates expression of c-Fos and c-Jun and the redox regulators, thioredoxin (Trx) and Redox factor-1 (Ref-1) and activates both AP-1 and NF-κB binding. Chronic exposure to 0.1 or 0.5 μM As(III) decreased c-Jun, c-Fos and Ref-1 protein levels and AP-1 and NF-κB binding activity, but increased Trx expression. Short term exposure to phorbol 12-myristate 13-acetate (TPA), a phorbol ester tumour promoter, or hydrogen peroxide (H2O2) also activates AP-1 and NF-κB binding. However, pre-treatment with As(III) prevents this increase. These results suggest that As(III) may alter AP-1 and NF-κB activity, in part, by up-regulating Trx and Ref-1. The different effects of short- versus long-term As(III) treatment on acute-phase response to oxidative stress reflect changes in the expression of Ref-1, c-Fos and c-Jun, but not Trx. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Toxicology (incl. Clinical Toxicology)
Objective Division:Health
Objective Group:Public Health (excl. Specific Population Health)
Objective Field:Environmental Health
Author:Snow, ET (Associate Professor Elizabeth Snow)
ID Code:42278
Year Published:2002
Web of Science® Times Cited:81
Deposited By:Health Sciences A
Deposited On:2007-06-13
Last Modified:2007-06-13
Downloads:0

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