Protective effect of heat shock protein 27 using protein transduction domain-mediated delivery on ischemia/reperfusion heart injury.

Abstract

Heat shock protein 27 (HSP27) is an intracellular stress protein with the cytoprotective effect for a variety of noxious stresses. In this study, using a protein delivery system, we demonstrated the potential cytoprotective effect of HSP27 as a therapeutic protein in cardiac cells and ischemia/reperfusion animal model. We constructed a recombinant HSP27 fused to the protein transduction domain (PTD) derived from HIV-1 TAT protein. Purified recombinant TAT-HSP27 protein was efficiently delivered to H9c2 cells, and its transduction showed cytoprotective effect against the hypoxic stress. Moreover, transduction of TAT-HSP27 also attenuated hypoxia-induced apoptosis, which was accompanied by reduced caspase-3 activity. In addition, intraperitoneal injection of TAT-HSP27 into rat resulted in efficient protein transduction in heart tissues, decreased infarcted myocardium (control vs TAT-HSP27, 39.1% vs 29.5%, P<0.05) and preserved heart function (fractional shortening, 15.6% vs 33.4%, P<0.05), as determined at 7 d after I/R. These results suggest that the PTD-mediated delivery of HSP27 protein may represent a potential therapeutic strategy as protein drug for ischemic heart diseases.

• Authors: Jun Hye Kwon, Jin-Bae Kim, Kyung-Hye Lee, Seok-Min Kang, Namsik Chung, Yangsoo Jang, Ji Hyung Chung
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 363 Issue 2 Pg. 399-404 (Nov 16 2007) ISSN: 0006-291X [Print] United States
• PMID: 17869218 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Heat-Shock Proteins

Topics

• Animals
• Cardiotonic Agents
• Genetic Therapy (methods)
• Heat-Shock Proteins (genetics, therapeutic use)
• Male
• Myocardial Reperfusion Injury (diagnostic imaging, therapy)
• Protein Structure, Tertiary
• Rats
• Rats, Sprague-Dawley
• Transduction, Genetic
• Transfection (methods)
• Treatment Outcome
• Ultrasonography
• Ventricular Dysfunction, Left (diagnostic imaging, prevention & control)