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Hu Y, Jin X, Snow ET: Effect of arsenic on transcription factor AP-1 and NF-kappaB DNA binding activity and related gene expression. Toxicol Lett. 2002 Jul 7;133(1):33-45. 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-kappa B) DNA binding activity. Short-term treatment with 0.1-5 microM 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-kappa B binding. Chronic exposure to 0.1 or 0.5 microM As (III) decreased c-Jun, c-Fos and Ref-1 protein levels and AP-1 and NF-kappa B binding activity, but increased Trx expression. Short term exposure to phorbol 12-myristate 13-acetate (TPA), a phorbol ester tumour promoter, or hydrogen peroxide (H (2) O (2)) also activates AP-1 and NF-kappa B binding. However, pre-treatment with As (III) prevents this increase. These results suggest that As (III) may alter AP-1 and NF-kappa B 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. |
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