title: EC-SOD induces apoptosis through COX-2 and galectin-7 in the epidermis.
abstract: BACKGROUND
  Extracellular superoxide dismutase (EC-SOD) is an anti-oxidant enzyme found in the extracellular matrix of tissues, and plays an important role in the prevention of many diseases caused by oxidative stress. However, other functions of EC-SOD in epidermis are not well known.
  
  
  OBJECTIVE
  We investigated the functions of EC-SOD in epidermis using keratinocyte cell line and EC-SOD transgenic mice.
  
  
  METHODS
  Expression of galectin-7 in pEC-SOD transfected cells or skin of EC-SOD transgenic mice was detected by western blot analysis. The percentage of apoptotic cells was determined by propidium iodide staining and subsequent FACS analysis. COX-2 siRNA or scrambled siRNA was transfected into HaCaT cells and western blot analysis was performed to detect pro-apoptotic protein levels.
  
  
  RESULTS
  The epidermis of EC-SOD transgenic mice was thinner than wild type mice. In addition, we showed that the thin epidermis of EC-SOD transgenic mice results from the apoptosis of epidermal cells. To elucidate which molecules are involved in EC-SOD-induced apoptosis, we utilized two-dimensional electrophoresis; the results showed that the epidermis of EC-SOD transgenic mice produces more galectin-7, a pro-apoptotic factor, than the wild type. Furthermore, we showed that the transfection of EC-SOD-expressing plasmids induces the production of galectin-7, and pro-apoptotic proteins in keratinocytes. This suggests that EC-SOD induces apoptosis through increased galectin-7 expression. Finally, we demonstrated that EC-SOD-induced galectin-7 results from the production of COX-2.
  
  
  CONCLUSIONS
  Our results imply that EC-SOD plays a role not only as a reactive oxygen species scavenger, but also as a pro-apoptotic factor via COX-2/galectin-7 pathways in the epidermis.
authors.affiliation: Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul 137-040, South Korea.
authors.forename: Joon-seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Yun sang
authors.initials: Ys
authors.lastname: Lee
authors.forename: Byeongwook
authors.initials: B
authors.lastname: Jeon
authors.forename: Yun jae
authors.initials: Yj
authors.lastname: Jeon
authors.forename: Hyun
authors.initials: H
authors.lastname: Yoo
authors.forename: Tae-Yoon
authors.initials: TY
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D005434:Flow Cytometry; D037161:Galectins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D034622:RNA Interference; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D037161:Galectins; C092525:LGALS7 protein, human; C490487:Lgals7 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D013482:Superoxide Dismutase