title: Peroxiredoxin I plays a protective role against UVA irradiation through reduction of oxidative stress.
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.
  
  
  CONCLUSIONS
  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.affiliation: Oral and Maxillofacial Surgery, Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
authors.affiliation: Environmental Molecular Biology, Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Oral and Maxillofacial Surgery, Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan.
authors.forename: Kahori
authors.initials: K
authors.lastname: Seto
authors.affiliation: Department of Environmental Molecular Biology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Warabi
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawachi
authors.affiliation: Department of Medical Science, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Shoda
authors.affiliation: Department of Neurophysiology, Faculty of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Tabuchi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Bukawa
authors.affiliation: Department of Environmental Molecular Biology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan. Electronic address: ytony@md.tsukuba.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Yanagawa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D002470:Cell Survival; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D054464:Peroxiredoxins
keywords: Apoptosis; Peroxiredoxin I; ROS; UVA; p53