title: Protective effects of intraperitoneal injection of TAT-SOD against focal cerebral ischemia/reperfusion injury in rats.
abstract: OBJECTIVE
  The intracellular superoxide anion has been shown to be involved in brain injury. TAT-Superoxide dismutase (TAT-SOD) can be transduced across the cell membrane to scavenge superoxide. This protein's unique properties make it a promising therapeutic candidate to attenuate cerebral damage. In this study, we sought further the understanding of the fusion protein's cerebral protective effects and the mechanism which is exerted in these effects.
  
  
  METHODS
  Male Sprague Dawley rats (n=100, 230±20 g) were divided randomly into five experimental groups: a sham group, a cerebral Ischemia/Reperfusion (I/R) group treated with saline (20 ml/Kg, i.p.), and three cerebral I/R groups treated with TAT-SOD (25 KU/ml/Kg, i.p.) at either 2h before I/R, 2h after I/R or 4h after I/R. Cerebral I/R injury was facilitated by inducing ischemia for two hours followed by 24h reperfusion. The levels of SOD, Malondialdehyde (MDA), and ATPase in cerebral tissues were determined. The apoptotic indexes were evaluated, and apoptosis genes were analyzed immunohistochemically.
  
  
  RESULTS
  TAT-SOD treatment significantly increased cerebral SOD and ATPase activities, decreased MDA content, and remarkably reduced apoptosis indexes. TAT-SOD treatments 2h before or after I/R significantly reduced caspase-3 and bax proteins and boosted bcl-2 protein, while the treatment at 4h after I/R showed no influence on the three proteins.
  
  
  CONCLUSIONS
  TAT-SOD treatment effectively enhanced cerebral antioxidant ability, reduced lipid peroxidation, preserved mitochondrial ATPase and thus inhibited nerve cell apoptosis. The effective treatment window extended from 2h before to 2h after I/R.
authors: Department of Bioscience and Biotechnology, Fuzhuo University, Fujian, PR China.
authors: Nanhui
authors: N
authors: Ye
authors: Shutao
authors: S
authors: Liu
authors: Yanyun
authors: Y
authors: Lin
authors: Pingfan
authors: P
authors: Rao
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000201:enzymology / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000032:analysis; D015696:Gene Products, tat / Q000008:administration & dosage / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: D015696:Gene Products, tat; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein; D013482:Superoxide Dismutase; D053148:Caspase 3; D000251:Adenosine Triphosphatases