Protein oxidative damage and heme oxygenase in sunlight-exposed human skin: roles of MAPK responses to oxidative stress

• Published in: The Tokai journal of experimental and clinical medicine Vol. 35; no. 4; p. 152
• Main Authors: Akasaka, Emiko, Takekoshi, Susumu, Horikoshi, Yosuke, Toriumi, Kentarou, Ikoma, Norihiro, Mabuchi, Tomotaka, Tamiya, Shiho, Matsuyama, Takashi, Ozawa, Akira
• Format: Journal Article
• Language: English
• Published: Japan 20.12.2010
• Subjects: Aged; Aged, 80 and over; Aldehydes - metabolism; Cysteine Proteinase Inhibitors - metabolism; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Heme Oxygenase (Decyclizing) - metabolism; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; Male; Mitogen-Activated Protein Kinases - metabolism; Oxidative Stress; p38 Mitogen-Activated Protein Kinases - metabolism; Signal Transduction - physiology; Skin - anatomy & histology; Skin - metabolism; Skin - pathology; Skin - radiation effects; Sunlight - adverse effects
• ISSN: 2185-2243

Oxidative stress derived from ultraviolet (UV) light in sunlight induces different hazardous effects in the skin, including sunburn, photo-aging and DNA mutagenesis. In this study, the protein-bound lipid peroxidation products 4-hydroxy-2-nonenal (HNE) and the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8OHdG) were investigated in chronically sun-exposed and sun-protected human skins using immunohistochemistry. The levels of antioxidative enzymes, such as heme oxygenase 1 and 2, Cu/Zn-SOD, Mn-SOD and catalase, were also examined. Oxidative stress is also implicated in the activation of signal transduction pathways, such as mitogen-activated protein kinase (MAPK). Therefore, the expression and distribution of phosphorylated p38 MAPK, phosphorylated Jun N-terminal kinase (JNK) and phosphorylated extracellular signal-regulated kinase (ERK) were observed. Skin specimens were obtained from the surgical margins. Chronically sunlight-exposed skin samples were taken from the ante-auricular (n = 10) and sunlight-protected skin samples were taken from the post-auricular (n = 10). HNE was increased in the chronically sunlight-exposed skin but not in the sunlight-protected skin. The expression of heme oxygenase-2 was markedly increased in the sunlight-exposed skin compared with the sun-protected skin. In contrast, the intensity of immunostaining of Cu/Zn-SOD, Mn-SOD and catalase was not different between the two areas. Phosphorylated p38 MAPK and phosphorylated JNK accumulated in the ante-auricular dermis and epidermis, respectively. These data show that particular anti-oxidative enzymes function as protective factors in chronically sunlight-exposed human skin. Taken together, our results suggest (1) antioxidative effects of heme oxygenase-2 in chronically sunlight-exposed human skin, and that (2) activation of p38 MAPK may be responsible for oxidative stress.