1. ¹Department of Dermatology, Friedrich Schiller University, Jena, Germany
2. ²Center for Molecular Biomedicine, Friedrich Schiller University, Jena, Germany
3. ³Department of Dermatology, Nagasaki University School of Medicine, Nagasaki, Japan
4. ⁴Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA

Correspondence: Dr Jens J. Thiele, Department of Dermatology, Boston University Medical Center, 609 Albany Street, Boston, Massachusetts 02118, USA. E-mail: jens.thiele@bmc.org

Received 17 April 2005; Revised 16 July 2005; Accepted 20 July 2005; Published online 2 March 2006.

Abstract

Recently, we reported that photoaging correlates well with the amount of oxidized protein accumulated in the upper dermis, while protein oxidation levels in the viable epidermis are very low. We hypothesized that this might be due to epidermal expression of the repair enzymes methionine sulfoxide reductases (MSRs). The expression of human methionine sulfoxide reductase A (MSRA) was investigated in HaCaT cells, primary human keratinocytes, and in human skin. High MSRA mRNA and protein levels as well as MSR activity were found in cultured human keratinocytes. MSRA was expressed in human epidermis, as shown by immunohistochemistry in healthy human skin. Repetitive in vivo exposure of human skin to solar-simulated light on 10 consecutive days (n=10 subjects) significantly increased epidermal MSRA expression. To further assess the functional relevance of the enzyme, its expression in response to UVB, UVA, and H₂O₂ was investigated in HaCaT cells. While UVB lowered protein expression of MSRA, an upregulation was observed in response to low doses of UVA and H₂O₂. In summary, MSRA represents the only enzyme so far identified in human skin that is capable of repairing oxidative protein damage. In addition to melanogenesis and DNA repair systems, a wavelength-specific activation of epidermal MSRA may be involved in epidermal photoprotection.