Peroxiredoxin I plays a protective role against UVA irradiation through reduction of oxidative stress

• Published in: Journal of dermatological science 2014-04, Vol.74 (1), p.9-17
• Main Authors: Ito, Takaaki, Kimura, Shintaro, Seto, Kahori, Warabi, Eiji, Kawachi, Yasuhiro, Shoda, Junichi, Tabuchi, Katsuhiko, Yamagata, Kenji, Hasegawa, Shogo, Bukawa, Hiroki, Ishii, Tetsuro, Yanagawa, Toru
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - metabolism; Apoptosis; Cell Survival; Dermatology; Fibroblasts - metabolism; Flow Cytometry; Homozygote; Mice; Mice, Knockout; Mitochondria - metabolism; Oxidative Stress; p53; Peroxiredoxin I; Peroxiredoxins - physiology; Reactive Oxygen Species - metabolism; ROS; Skin - metabolism; Skin - radiation effects; Tumor Suppressor Protein p53 - metabolism; Ultraviolet Rays; UVA
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2013.12.002

Abstract Background Exposure of skin to long-wave UV radiation (UVA) increases the cellular levels of reactive oxygen species (ROS), which have been linked to apoptosis induction through the damage of lipids, proteins, and nucleic acids. Peroxiredoxin I (Prx I) is one of a family of antioxidant proteins that plays a protective role against oxidative damage; however the role of Prx I in UVA-induced damage remains to be clarified. Objective Here we investigated the protective role of Prx I against UVA-induced changes using mouse embryonic fibroblasts (MEFs) derived from Prx I homozygous knockout (Prx I (−/−)) mice. Methods Prx I (−/−) and wild-type (Prx I (+/+)) MEFs were subjected to UVA irradiation, and the resulting apoptosis was analyzed using flow cytometry, quantitative real-time PCR, and western blotting. Results Prx I (−/−) MEFs showed enhanced sensitivity to UVA treatment, exhibiting increased apoptosis and ROS production compared to Prx I (+/+) MEFs. Consistent with the increase in apoptosis, p53 expression was significantly higher, while Bcl-2, Bcl-xL, and Nrf2 expressions were all lower in Prx I (−/−) versus (+/+) MEFs. The UVA-induced inflammatory response was upregulated in Prx I (−/−) MEFs, as indicated by increased expressions of IκB, TNFα, and IL-6. Evidence was presented indicating that Prx I impacts these pathways by modifying critical signaling intermediates including p53, IκB, and Nrf2. Conclusion Our results indicate that Prx I plays a protective role against UVA-induced oxidative damage by controlling ROS accumulation. Both the UVA-induced apoptotic and inflammatory signals were found to be modulated by Prx I.