Inhibitory effects of deferoxamine on UVB-induced AP-1 transactivation

Production of reactive oxygen species (ROS) by iron can contribute directly to DNA and protein damage and may contribute to cell signaling and prolife ration. We have examined the effects of the iron(III) chelator deferroxamin e (DFO) and iron (FeCl3) on UVB (290-320 nm)-induced activator protein 1 (A P-1) signaling. The ability of DFO to inhibit UVB-induced AP-1 transactivat ion was tested in a human keratinocyte cell line stably transfected with a luciferase reporter driven by a single AP-1 element. DFO treatment 24 h pri or to UVB irradiation reduced UVB-induced AP-1 transactivation by similar t o 80%, with the effect of DFO diminishing as pre-treatment time was shorten ed, Treatment with FeCl3 a minimum of 6 h prior to UVB potentiated the UVB induction of AP-1 transactivation by 2-3-fold. DFO was able to ablate both the UVB induction of AP-1 transactivation as well as the potentiation by Fe Cl3. The antioxidants Trolox and N-acetyl cysteine were both able to inhibi t UVB-induced AP-1 transactivation and Trolox was able to inhibit the poten tiation of UVB-induced AP-1 by FeCl3. These results indicate that UVB-induc ed AP-1 activation may be in part due to oxidant effects of UVB and interce llular iron.