Takaaki Ito1, Shintaro Kimura2, Kahori Seto1, Eiji Warabi3, Yasuhiro Kawachi4, Junichi Shoda5, Katsuhiko Tabuchi6, Kenji Yamagata7, Shogo Hasegawa7, Hiroki Bukawa7, Tetsuro Ishii3, Toru Yanagawa8. 1. Oral and Maxillofacial Surgery, Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan. 2. Environmental Molecular Biology, Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan. 3. Department of Environmental Molecular Biology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan. 4. Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan. 5. Department of Medical Science, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan. 6. Department of Neurophysiology, Faculty of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan. 7. Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan. 8. Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan. Electronic address: ytony@md.tsukuba.ac.jp.
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.
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.
Authors: M G Sharapov; S V Gudkov; A E Gordeeva; O E Karp; V E Ivanov; O V Shelkovskaya; V I Bruskov; V I Novoselov; E E Fesenko Journal: Dokl Biochem Biophys Date: 2016-05-20 Impact factor: 0.788