Distinct effects of thioredoxin and antioxidants onthe activation of transcription factors NF-kappa B and AP-1.

Abstract

The tanption factors NF-KB and AP-1 have been Implicated in the inducible expression of a variety of gen involved in to oxidative stress and cellular defense mechanisms. Here, we report that thioredoxin, an important cellular protein oxidoreductase with antoxidant activity, exerts different effects on the activation of NF-icB and AP-1. Transient expression or exogenous application of thioredoxin resulted in a dose-dependent inhibition of NF-KB activly, as demonstrated in gel shift and transactivation experiments. AP-1-dependent transactivation, in contrast, was sltrongy enhanced by thioredoxin. A similar increase of AP-1 actiity was also observed with other, structurally unrelated antioxidants such as pyrrolidine dithiocarbamate and butylated hydroxyanisole, indicating that the thioredoxin-induced increase of AP-1 activation was indeed based on an antioidant effect. Moreover, the stimulatoy effect on AP-1 activity was found to involve de novo t cipton of the c-jun and c-fos components but to be independent of protein kinase C activation. These results suggest that thioredoxin plays an important role in the regulation of transcriptional processes and oppositely affects NF-ucB and AP-1 activation.

Strong and prolonged induction of c-jun and c-fos proto-oncogenes by photodynamic therapy

“…Stronger DNA-binding was caused by the antioxidant state (Meyer et al. 1993;Schenk et al, 1994;Li and Jaiswal, 1994). Superoxide anions and hydrogen peroxide were found to be weak inducers of AP-1 binding (Amstad et al, 1992;Devary et al, 1991).…”

Mobilization of iron from cellular ferritin by ascorbic acid in neuroblastoma SK‐N‐SH cells: an EPR study

“…However, iron in its ferrous form may also be cytotoxic because of its reaction with H202 yielding various reactive oxygen species [36,38]. These naturally occurring oxygen metabolites are believed to have a dual role in the cellular metabolism: they are either involved in regulatory processes like the activation of NF-n-B [39,40] and the Bcl-2 protein preventing apoptosis [41], or they may induce oxidative damage to cell membranes or nucleic acids [42]. Normally, iron is stored in ferritin to prevent cell injury [13].…”

Redox signalling by transcription factors NF-κB and AP-1 in lymphocytes

“…In a catalase-overexpressing cell line, NF-KB activation was substantially suppressed compared with the parental cell line, whereas it was superinduced in a Cu/Zn-SOD-overexpressing cell line [24]. Likewise, overexpression of thioredoxin or addition of recombinant thioredoxin to the cell culture medium prevented NF-KB activation by the protein kinase C activator phorbol 12-myristate 13-acetate [25].…”