title: Protein oxidative damage and heme oxygenase in sunlight-exposed human skin: roles of MAPK responses to oxidative stress.
abstract: 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.
authors.affiliation: Department of Dermatology, Tokai University School of Medicine, Isehara, Kanagawa, Japan. emiko-a@is.icc.u-tokai.ac.jp
authors.forename: Emiko
authors.initials: E
authors.lastname: Akasaka
authors.forename: Susumu
authors.initials: S
authors.lastname: Takekoshi
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Horikoshi
authors.forename: Kentarou
authors.initials: K
authors.lastname: Toriumi
authors.forename: Norihiro
authors.initials: N
authors.lastname: Ikoma
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Mabuchi
authors.forename: Shiho
authors.initials: S
authors.lastname: Tamiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Akira
authors.initials: A
authors.lastname: Ozawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000033:anatomy & histology / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D013472:Sunlight / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C027576:4-hydroxy-2-nonenal