H2O2 accumulation by catalase reduction changes MAP kinase signaling in aged human skin in vivo.
To understand the molecular alterations occurring during the aging process, we compared mitogen-activated protein (MAP) kinase activities in the intrinsically aged and photoaged skins in the same individuals. Furthermore, we investigated the molecular events related to MAP kinase changes in intrinsically aged and photoaged skins. We found that extracellular-signal-regulated kinase (ERK) activity in photoaged skin was reduced, and that the activities of c-Jun N-terminal kinase (JNK) and p38 kinase were increased compared with intrinsically aged skin in the same individuals. Phospho-c-Jun levels and activator protein 1 activities in photoaged skin were also higher than in intrinsically aged skin. Moreover, catalase activity was found to be much reduced in primary dermal fibroblasts from photoaged skin, and as a result, H2O2 accumulated more in primary dermal fibroblasts in photoaged skin. In addition, treating primary dermal fibroblasts from photoaged skin with catalase reduced H2O2 levels, reversed aging-dependent MAP kinase changes, and inhibited matrix metalloproteinase (MMP)-1 expression. Our results indicate that the accumulation of reactive oxygen species due to catalase attenuation may be a critical aspect of the MAP kinase signaling changes that may lead to skin aging and photoaging in human skin in vivo. Thus, the induction and regulation of endogenous antioxidant enzymes including catalase may offer a strategy for preventing and treating skin aging.
Shin
Mi Hee
MH
Department of Dermatology, Laboratory of Cutaneous Agining Research, Clinical Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Rhie
Gi-eun
GE
Kim
Yeon Kyung
YK
Park
Chi-Hyun
CH
Cho
Kwang Hyun
KH
Kim
Kyu Han
KH
Eun
Hee Chul
HC
Chung
Jin Ho
JH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002374:Catalase / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology / Q000201:enzymology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015595:Skin Aging / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D006861:Hydrogen Peroxide; D002374:Catalase; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1