title: Therapeutic evaluation of HIV transduction basic domain-conjugated superoxide dismutase solution on suppressive effects of the formation of peroxynitrite and expression of COX-2 in murine skin.
abstract: BACKGROUND
  Homeostasis of reactive oxygen species (ROS) in the skin is regulated by antioxidant defenses. The inflammatory states of skin diseases which range from acute rashes to chronic conditions are related to the level of ROS. The involvement of superoxide dismutase (SOD) in restoring the antioxidant capacity can then neutralize the inflammatory response.
  
  
  RESULTS
  We found that denatured Tat-SOD formulated in an aqueous medium could be delivered into mouse skin and the penetration signals of Tat-SOD were detected in the epidermis and dermis. According to immunohistochemical staining, Tat-SOD successfully suppressed inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), the expression of sodium nitroferricyanide (SNP)-induced cyclooxygenase-2 (COX-2), and the production of nitrotyrosine proteins. In nerve growth factor (NGF) induced differentiated PC12 pheochromocytoma cells, we demonstrated that the denatured Tat-SOD regained its antioxidant activity and effectively protected PC12 cells from DNA fragmentation induced by paraquat. Using a luciferase reporter assay, the data was shown Tat-SOD protected PC12 cells from ROS damage, through suppression of COX-2 or nuclear factor-κB (NF-κB) activity occurred at the transcriptional level.
  
  
  CONCLUSIONS
  We showed that Tat-SOD inhibited SNP-induced COX-2 expression similarly to celecoxib and prevented the formation of peroxynitrite as 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. The results suggest that denatured Tat-SOD solution may perform potential protein therapy for patients suffering from disorders related to ROS.
authors.affiliation: Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan.|Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Tsang-Pai
authors.initials: TP
authors.lastname: Liu
authors.affiliation: Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Chou
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Chiu
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan. chenctsu@tmu.edu.tw.
authors.forename: Chien-Tsu
authors.initials: CT
authors.lastname: Chen
mesh_terms: D000818:Animals; D000068579:Celecoxib / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D003872:Dermatitis / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D016716:PC12 Cells; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D014161:Transduction, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis / Q000235:genetics
chemical_list: D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D030421:Peroxynitrous Acid; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D000068579:Celecoxib