title: Transduced PEP-1-heme oxygenase-1 fusion protein protects against intestinal ischemia/reperfusion injury.
abstract: BACKGROUND
  Heme oxygenase-1 (HO-1) has been shown to have antioxidant and anti-apoptotic properties. The present study transduced HO-1 protein into intestinal tissues using PEP-1, a cell-penetrating peptide, and investigated its potentiality in prevention against intestinal ischemia/reperfusion (I/R) injury.
  
  
  METHODS
  PEP-1-HO-1 fusion protein was administered intravenously to explore the time and dose characteristics through measuring serum HO-1 levels. Twenty-four male Sprague-Dawley rats were randomly divided into three groups: sham, intestinal I/R (II/R), II/R + PEP-1-HO-1 fusion protein (HO). The model was established by occluding the superior mesenteric artery for 45 min followed by 120 min reperfusion. In HO group, PEP-1-HO-1 was administered intravenously 30 min before ischemia, whereas animals in sham and II/R groups received the equal volume of physiological saline. After the experiment, the intestines were harvested for determination of histologic injury, wet/dry ratio, enzyme activity, apoptosis, and His-probe protein (one part of PEP-1-HO-1).
  
  
  RESULTS
  Levels of serum HO-1 were dose- and time-dependent manner after intravenous injection of PEP-1-HO-1. I/R caused deterioration of histologic characteristics and increases in histologic injury scoring, wet/dry ratio, myeloperoxidase activity, malondialdehyde, and intestinal apoptosis. These changes were also accompanied by a decrease in superoxide dismutase activity (P < 0.05). PEP-1-HO-1 treatment significantly reversed these changes (P < 0.05). Furthermore, His-probe protein expression was only detected in PEP-1-HO-1-treated animals.
  
  
  CONCLUSIONS
  Treatment of PEP-1-HO-1 attenuates intestinal I/R injury, which might be attributable to its antioxidant and anti-apoptotic roles of HO-1.
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. Electronic address: hexh1220@aliyun.com.
authors.forename: Xiang-Hu
authors.initials: XH
authors.lastname: He
authors.affiliation: Department of Anesthesiology, Shenzhen Boan Maternity and Child Health hospital, Shenzhen, China.
authors.forename: Xue-Tao
authors.initials: XT
authors.lastname: Yan
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Yan-Lin
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Cheng-Yao
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Zong-Ze
authors.initials: ZZ
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000097:blood* / Q000235:genetics*; D007275:Injections, Intravenous; D007422:Intestines / Q000098:blood supply* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D010636:Phenols / Q000097:blood; D010936:Plant Extracts / Q000097:blood / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000097:blood* / Q000235:genetics*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology
chemical_list: D010636:Phenols; D010936:Plant Extracts; D011993:Recombinant Fusion Proteins; C501911:antioxidant biofactor AOB; D008315:Malondialdehyde; D009195:Peroxidase; D051547:Heme Oxygenase-1; C561500:PEP-1-heme oxygenase-1 fusion protein
keywords: Anti-apoptotic; Antioxidant; Cell-penetrating peptide; Fusion protein; Heme oxygenase-1; Intestine; Ischemia/reperfusion; Lipid peroxidation; Myeloperoxidase; Rat