title: The repair enzyme peptide methionine-S-sulfoxide reductase is expressed in human epidermis and upregulated by UVA radiation.
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 H(2)O(2) was investigated in HaCaT cells. While UVB lowered protein expression of MSRA, an upregulation was observed in response to low doses of UVA and H(2)O(2). 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.
authors.affiliation: Department of Dermatology, Friedrich Schiller University, Jena, Germany.
authors.forename: Fumihide
authors.initials: F
authors.lastname: Ogawa
authors.forename: Christina S
authors.initials: CS
authors.lastname: Sander
authors.forename: Alfred
authors.initials: A
authors.lastname: Hansel
authors.forename: Wolf
authors.initials: W
authors.lastname: Oehrl
authors.forename: Hubert
authors.initials: H
authors.lastname: Kasperczyk
authors.forename: Peter
authors.initials: P
authors.lastname: Elsner
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shimizu
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Heinemann
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Thiele
mesh_terms: D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015603:Keratinocytes / Q000201:enzymology; D051150:Methionine Sulfoxide Reductases; D010088:Oxidoreductases / Q000235:genetics*; D017382:Reactive Oxygen Species; D012867:Skin / Q000201:enzymology* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase