Effect of arsenic on transcription factor AP-1 and NF-kappa B DNA binding activity and related gene expression

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-kappaB) DNA binding activity. Short-term treatment with 0.1-5 muM 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-kappaB binding. Chronic exposure to 0.1 or 0.5 muM As(III) decreased c-Jun, c-Fos and Ref-1 protein levels and AP-1 and NF-KB 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-kappaB binding. However, pre-treatment with As(III) prevents this increase. These results suggest that As(III) may alter AP-1 and NF-KB 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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved