title: Treatment of experimental cerebral vasospasm by protein transduction of heme oxygenase 1 (HO-1) conjugated to a residue of 11 arginines.
abstract: BACKGROUND
  Many kinds of proteins can be transduced into various cells by conjugation with 10-20 amino acid peptides. A sequence of 11 consecutive arginine groups (11R) is one of the most efficient protein transduction domains (PTD). We used the 32-kDa heat shock protein heme oxygenase-1 (HO-1) as a therapeutic protein for experimental cerebral vasospasm. This protein is an enzyme of the heme-catabolism and cleaves heme to form biliverdin and carbon monoxide (CO). HO-1 has known vascular relaxing properties. We examined the transduction efficacy and antispastic therapeutic effect of 11R fused HO-1 protein in cerebral arteries.
  
  
  METHODS
  11R fused HO-1 protein was expressed purified. An MTT assay was used to evaluate the cytotoxicity of 11R-HO-1. An antispastic effect was investigated in a rat model of experimental subarachnoid hemorrhage by measuring basilar artery diameters 4 h after the injection of 11R-HO-1 into the cisterna.
  
  
  RESULTS
  Expression and purification of 11R-HO-1 could be successfully effected. Transduction into the basilar artery was also successful. 11R-HO-1 protein has the positive effect of attenuating cerebral vasospasm.
  
  
  CONCLUSIONS
  These results suggest that the 11R-HO-1 protein transduction method has a potential to treat cerebral vasospasm.
authors.affiliation: Department of Neurosurgery, Heinrich Heine University, Düsseldorf, Germany. tomoyuki.ogawa@uni-duesseldorf.de
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ogawa
authors.forename: Daniel
authors.initials: D
authors.lastname: Hänggi
authors.forename: Hans-Jakob
authors.initials: HJ
authors.lastname: Steiger
mesh_terms: D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts; D013844:Thiazoles; D020301:Vasospasm, Intracranial / Q000188:drug therapy*
chemical_list: D013778:Tetrazolium Salts; D013844:Thiazoles; D001120:Arginine; D051547:Heme Oxygenase-1; C022616:thiazolyl blue