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(American Journal of Pathology. 2006;169:1194-1205.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060119

Peroxiredoxin 6 Is a Potent Cytoprotective Enzyme in the Epidermis

Angelika Kümin*, Christine Huber*, Thomas Rülicke{dagger}, Eckhard Wolf{ddagger} and Sabine Werner*

From the Department of Biology,* Institute of Cell Biology, ETH Zurich, Zurich, Switzerland; the Institute of Laboratory Animal Science and Austrian Center for Biomodels and Transgenetics,{dagger} University of Veterinary Medicine Vienna, Vienna, Austria; and the Institute of Molecular Animal Breeding and Biotechnology,{ddagger} Gene Center, Ludwig-Maximilians-University, Munich, Germany

Peroxiredoxin 6 is an enzyme that detoxifies hydrogen peroxide and various organic peroxides. In previous studies we found strongly increased expression of peroxiredoxin 6 in the hyperproliferative epidermis of wounded and psoriatic skin, suggesting a role of this enzyme in epidermal homeostasis. To address this question, we generated transgenic mice overexpressing peroxiredoxin 6 in the epidermis. Cultured keratinocytes from transgenic mice showed enhanced resistance to the toxicity of various agents that induce oxidative stress. However, overexpression of peroxiredoxin 6 did not affect skin morphogenesis or homeostasis. On skin injury, enhancement of wound closure was observed in aged animals. Most importantly, peroxiredoxin 6 overexpression strongly reduced the number of apoptotic cells after UVA or UVB irradiation. These findings demonstrate that peroxiredoxin 6 protects keratinocytes from cell death induced by reactive oxygen species in vitro and in vivo, suggesting that activation of this enzyme could be a novel strategy for skin protection under stress conditions.




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