Protective effect of heat shock protein 27 using protein transduction domain-mediated delivery on ischemia/reperfusion heart injury.
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.
Kwon
Jun Hye
JH
Yonsei Research Institute of Aging Science, Yonsei University, Seoul 120-749, Republic of Korea.
Kim
Jin-Bae
JB
Lee
Kyung-Hye
KH
Kang
Seok-Min
SM
Chung
Namsik
N
Jang
Yangsoo
Y
Chung
Ji Hyung
JH
D000818:Animals; D002316:Cardiotonic Agents; D015316:Genetic Therapy / Q000379:methods*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging* / Q000628:therapy*; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000517:prevention & control*
D002316:Cardiotonic Agents; D006360:Heat-Shock Proteins