Journal Article

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

Kim Kramer-Stickland, Andrew Edmonds, Warner B. Bair and G.Tim Bowden

in Carcinogenesis

Volume 20, issue 11, pages 2137-2142
Published in print November 1999 | ISSN: 0143-3334
Published online November 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.11.2137
Inhibitory effects of deferoxamine on UVB-induced AP-1 transactivation

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Production of reactive oxygen species (ROS) by iron can contribute directly to DNA and protein damage and may contribute to cell signaling and proliferation. We have examined the effects of the iron(III) chelator deferroxamine (DFO) and iron (FeCl3) on UVB (290–320 nm)-induced activator protein 1 (AP-1) signaling. The ability of DFO to inhibit UVB-induced AP-1 transactivation 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 prior to UVB irradiation reduced UVB-induced AP-1 transactivation by ~80%, with the effect of DFO diminishing as pre-treatment time was shortened. 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 FeCl3. The antioxidants Trolox and N-acetyl cysteine were both able to inhibit UVB-induced AP-1 transactivation and Trolox was able to inhibit the potentiation of UVB-induced AP-1 by FeCl3. These results indicate that UVB-induced AP-1 activation may be in part due to oxidant effects of UVB and intercellular iron.

Keywords: AP-1, activator protein 1; DFO, deferoxamine; DMEM, Dulbecco's modified Eagle's medium; EGTA, ethylene glycol tetraacetic acid; HCL14, HaCaT cells containing AP-1 regulated luciferase reporter gene; NAC, N-acetyl cysteine; RLU, relative light units; ROS, reactive oxygen species; Trolox-Me, Trolox methyl ether.

Journal Article.  5568 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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