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.

Functional characterization of the Aspergillus nidulans methionine sulfoxide reductases (msrA and msrB)

“…(Kantorow et al, 2004;Marchetti et al, 2006), retinal pigmented cells (Sreekumar et al, 2005), and human fibroblasts (Picot et al, 2005). Another interesting feature of the MsrA is its up-regulation in human skin in response to UV irradiation and hydrogen peroxide, suggesting a role of MsrA in photoprotection in epidermis (Ogawa et al, 2006;Schallreuter et al, 2006;Picot et al, 2007). We extended these studies by showing that Msr null mutants are not only sensitive to UV light but also have their transcripts accumulated in the presence of DNA damaging agents.…”

“…Recently, it was shown that the peptide methionine-S-sulfoxide reductase is expressed in human epidermis and upregulated by UVA (ultraviolet A) radiation (Ogawa et al, 2006;Schallreuter et al, 2006;Picot et al, 2007). To investigate a possible role of A. nidulans in UV-sensitivity, quiescent and germinating conidia from wild type and mutant strains were exposed to different UV light dosages.…”

The protein truncation caused by fusion of PEP-1 peptide and protective roles of transduced PEP-1-MsrA in skin cells

“…MsrA and MsrB proteins are present in skin cells including keratinocytes and melanocytes (12,13), but their functional roles in these cells are unclear. In this work, PEP-1-MsrA fusion protein could be rapidly delivered (＜15 min) into keratinocyte cells.…”

“…Skin serves as the first line of defense in protecting from the deleterious effects of ultraviolet (UV) radiation and other environmental oxidants. The MsrA and MsrB proteins are expressed in epidermal cells including keratinocytes and melanocytes (12,13), but the protective roles of these proteins have not been demonstrated in skin cells.…”

Increasing levels of serum antioxidant status, total antioxidant power, in systemic sclerosis

“…To counteract oxidative stress to lipid, proteins, and DNA, organisms are equipped with antioxidant defense mechanism that composed of enzymatic and nonenzymatic antioxidants [8][9][10]. Antioxidant enzymes include the families of superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferase, and thioredoxin.…”