THIOREDOXIN PEROXIDASE (NATURAL-KILLER ENHANCING FACTOR) REGULATION OF ACTIVATOR PROTEIN-1 FUNCTION IN ENDOTHELIAL-CELLS

Thioredoxin peroxidase-l (TxP-1), originally cloned as natural killer enhancing factor-B, belongs to a highly conserved antioxidant family. Tumor necrosis factor-alpha (TNF) activates the expression of activato r protein-1 (AP-1) responsive genes. We show here that over-expression of TxP-1 blocks TNF-induced AP-1 activation in endothelial ECV304 cel ls, which was demonstrated by three independent experimental protocols : electromobility shift assay with AP-1 oligonucleotide probe; reporte r gene expression with AP-1 binding site, and interleukin-8 production , which is dependent on AP-1. These results are consistent with the ro le of TxP-1 as an antioxidant and the previous reports that TNF-induce d reactive oxygen species were responsible for AP-1 activation. (C) 19 98 Academic Press.