Open AccessDistinct effects of thioredoxin and antioxidants onthe activation of transcription factors NF-kappa B and AP-1.
Author(s) -
Heike Schenk,
Matthias Klein,
Wilhelm Erdbrügger,
Wulf Dröge,
Klaus SchulzeOsthoff
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.5.1672
Subject(s) - transactivation , thioredoxin , pyrrolidine dithiocarbamate , transcription factor , nfkb1 , antioxidant , chemistry , nf κb , oxidative stress , microbiology and biotechnology , ap 1 transcription factor , signal transduction , biochemistry , biology , gene
The transcription factors NF-kappa B and AP-1 havebeen implicated in the inducible expression of a variety of genes involved inresponses to oxidative stress and cellular defense mechanisms. Here, we reportthat thioredoxin, an important cellular protein oxidoreductase with antioxidantactivity, exerts different effects on the activation of NF-kappa B and AP-1.Transient expression or exogenous application of thioredoxin resulted in adose-dependent inhibition of NF-kappa B activity, as demonstrated in gel shiftand transactivation experiments. AP-1-dependent transactivation, in contrast wasstrongly enhanced by thioredoxin. A similar increase of AP-1 activity was alsoobserved with other, structurally unrelated antioxidants such as pyrrolidinedithiocarbamate and butylated hydroxyanisole, indicating that thethioredoxin-induced increase of AP-1 activation was indeed based on anantioxidant effect. Moreover, the stimulatory effect on AP-1 activity was foundto involve de novo transcription of the c-jun and c-fos components but to beindependent of protein kinase C activation. These results suggest thatthioredoxin plays an important role in the regulation of transcriptionalprocesses and oppositely affects NF-kappa B and AP-1 activation.