Distinct effects of thioredoxin and antioxidants on the activation of transcription factors NF-kappa B and AP-1.
The transcription factors NF-kappa B and AP-1 have been implicated in the inducible expression of a variety of genes involved in responses to oxidative stress and cellular defense mechanisms. Here, we report that thioredoxin, an important cellular protein oxidoreductase with antioxidant activity, exerts different effects on the activation of NF-kappa B and AP-1. Transient expression or exogenous application of thioredoxin resulted in a dose-dependent inhibition of NF-kappa B activity, as demonstrated in gel shift and transactivation experiments. AP-1-dependent transactivation, in contrast was strongly enhanced by thioredoxin. A similar increase of AP-1 activity 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 antioxidant effect. Moreover, the stimulatory effect on AP-1 activity was found to involve de novo transcription 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-kappa B and AP-1 activation.
Schenk
H
H
Division of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany.
Klein
M
M
Erdbrügger
W
W
Dröge
W
W
Schulze-Osthoff
K
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D015342:DNA Probes / Q000235:genetics; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D013879:Thioredoxins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects
D000975:Antioxidants; D015342:DNA Probes; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D011759:Pyrrolidines; D011993:Recombinant Fusion Proteins; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D013879:Thioredoxins; D013755:Tetradecanoylphorbol Acetate