title: 8-Oxo-2'-deoxyguanosine ameliorates UVB-induced skin damage in hairless mice by scavenging reactive oxygen species and inhibiting MMP expression.
abstract: BACKGROUND
  Skin is uniquely vulnerable to damage caused by reactive oxygen species (ROS), which are most commonly produced in response to ultraviolet (UV) light. ROS generated at injury sites play an important role in modulating the inflammatory response. Besides inhibiting Rac, 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) has also shown notable antioxidant action.
  
  
  OBJECTIVE
  We tested whether 8-oxo-dG could protect skin from UVB-induced damage by scavenging ROS.
  
  
  METHODS
  HaCaT cells and hairless mice were irradiated with 15 and 180 mJ/cm(2) narrow-spectrum UVB, respectively. ROS generation was detected through incubation with DCFDA and confocal microscopy. Western blot analyses and immunohistochemistry were performed to verify the activities of ERK, JNK, p38, ATF-2, and c-Jun, and the expression of matrix metalloproteinases (MMPs), in UVB-irradiated HaCaT cells and murine skin. Hydrogen peroxide production and protein carbonyl concentrations were measured in UVB-damaged mouse skin. MMP-1 and MMP-9 expression in UVB-irradiated HaCaT cells was measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR).
  
  
  RESULTS
  In UVB-irradiated HaCaT cells, 8-oxo-dG inhibited ROS production, subsequent activation of mitogen-activated protein kinase (MAPK), ATF-2, and c-Jun, and MMP expression. It also prevented UV-induced skin reactions in hairless mice, inhibiting the increase in protein carbonyl content, activation of MAPKs, ATF-2, and c-Jun, the increases in MMP-9 and -13 expression, and epidermal hyperplasia.
  
  
  CONCLUSIONS
  8-oxo-dG can be considered an endogenous antioxidant and its potent antioxidant activity might be a beneficial property that could be exploited to protect skin from ROS-associated photodamage.
authors: Department of Pharmacology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Republic of Korea.
authors: Jin-Ku
authors: JK
authors: Lee
authors: Seong-Hee
authors: SH
authors: Ko
authors: Sang-Kyu
authors: SK
authors: Ye
authors: Myung-Hee
authors: MH
authors: Chung
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015595:Skin Aging / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; D003849:Deoxyguanosine