UV-induced expression of GADD45 is mediated by an oxidant sensitive pathway in cultured human keratinocytes and in human skin in vivo
| Autor: | Y Shao, YS Wan, G Fisher, Y Xu, Z Wang, J Voorhees |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Keratinocytes Antioxidant Ultraviolet Rays medicine.medical_treatment Human skin Oxidative phosphorylation Onium Compounds In vivo Genetics medicine Humans RNA Messenger Northern blot Enzyme Inhibitors Receptor Cells Cultured Skin chemistry.chemical_classification Reactive oxygen species NADPH oxidase biology Intracellular Signaling Peptides and Proteins Proteins Dose-Response Relationship Radiation Free Radical Scavengers Hydrogen Peroxide General Medicine Oxidants Molecular biology Acetylcysteine ErbB Receptors Gene Expression Regulation chemistry biology.protein Reactive Oxygen Species Interleukin-1 Signal Transduction |
| Zdroj: | International Journal of Molecular Medicine. |
| ISSN: | 1791-244X 1107-3756 |
| Popis: | The expression of GADD45 was examined in cultured skin keratinocytes and in human skin in vivo following UV irradiation. Northern blot analysis revealed that UV-induced the expression of GADD45 (alpha, beta, gamma) in a time- and dose-dependent manner. Messenger RNA of GADD45 (alpha, beta, gamma) increased within 30 min, peaked at 4 h and remained elevated for at least 8 h following UV irradiation in vitro and in vivo. Maximal induction of GADD45alpha was approximately 5-fold compared to the level in sham-irradiated controls. Similarly H2O2 and IL-1 also induced GADD45alpha expression in cultured human keratinocytes. The kinetics of induction of GADD45alpha by H2O2, IL-1beta and UV were very similar. Interestingly, UV-induced GADD45alpha expression was inhibited by diphenylene iodonium (DPI), an inhibitor of NADPH oxidase, and antioxidant, N-acetyl-L-cysteine (NAC), indicating the involvement of reactive oxygen species in UV signaling. Previously we have shown that EGF receptor activation by UV is prerequisite for subsequent activation of NADPH oxidase and generation of reactive oxygen species. We therefore examined the effect of EGF receptor inhibitor on UV-induced GADD45alpha expression. Our results showed that PD168393, a potent EGF receptor inhibitor, blocked UV-induced GADD45alpha expression. Collectively, our data suggest that UV-induced GADD45alpha expression occur via an EGF receptor-mediated oxidative pathway sensitive to antioxidant regulation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|