Effect of arsenic on transcription factor AP-1 and NF-kappaB 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-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.
Hu
Yu
Y
School of Biological and Chemical Sciences, Deakin University, 221 Burwood Highway, Burwood, Vic. 3125, Australia.
Jin
Ximei
X
Snow
Elizabeth T
ET
D018053:Arsenites / Q000633:toxicity*; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017670:Sodium Compounds / Q000633:toxicity*; D018808:Transcription Factor AP-1 / Q000187:drug effects* / Q000378:metabolism
D018053:Arsenites; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D017670:Sodium Compounds; D018808:Transcription Factor AP-1; C017947:sodium arsenite; D004247:DNA