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In Vivo Protein Transduction: Delivery of PEP-1-SOD1 Fusion Protein into Myocardium Efficiently Protects against Ischemic Insult

  • Zhang, You-en (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College) ;
  • Wang, Jia-ning (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College) ;
  • Tang, Jun-ming (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College) ;
  • Guo, Ling-yun (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College) ;
  • Yang, Jian-ye (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College) ;
  • Huang, Yong-zhang (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College) ;
  • Tan, Yan (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College) ;
  • Fu, Shou-zhi (Department of Emergency, Renmin Hospital, Yunyang Medical College) ;
  • Kong, Xia (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College) ;
  • Zheng, Fei (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College)
  • Received : 2008.08.08
  • Accepted : 2008.12.03
  • Published : 2009.02.28

Abstract

Myocardial ischemia-reperfusion injury is a medical problem occurring as damage to the myocardium following blood flow restoration after a critical period of coronary occlusion. Oxygen free radicals (OFR) are implicated in reperfusion injury after myocardial ischemia. The antioxidant enzyme, Cu, Zn-superoxide dismutase (Cu, Zn-SOD, also called SOD1) is one of the major means by which cells counteract the deleterious effects of OFR after ischemia. Recently, we reported that a PEP-1-SOD1 fusion protein was efficiently delivered into cultured cells and isolated rat hearts with ischemia-reperfusion injury. In the present study, we investigated the protective effects of the PEP-1-SOD1 fusion protein after ischemic insult. Immunofluorescecnce analysis revealed that the expressed and purified PEP-1-SOD1 fusion protein injected into rat tail veins was efficiently transduced into the myocardium with its native protein structure intact. When injected into Sprague-Dawley rat tail veins, the PEP-1-SOD1 fusion protein significantly attenuated myocardial ischemia-reperfusion damage; characterized by improving cardiac function of the left ventricle, decreasing infarct size, reducing the level of malondialdehyde (MDA), decreasing the release of creatine kinase (CK) and lactate dehydrogenase (LDH), and relieving cardiomyocyte apoptosis. These results suggest that the biologically active intact forms of PEP-1-SOD1 fusion protein will provide an efficient strategy for therapeutic delivery in various diseases related to SOD1 or to OFR.

Keywords

References

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