Transduced Heme Oxygenase-1 Fusion Protein Reduces Renal Ischemia/Reperfusion Injury Through Its Antioxidant and Antiapoptotic Roles in Rats

Introduction. Heme oxygenase-1 (HO-1) has a protective role against ischemia/reperfusion (I/R) injury. Methods. We produced an HO-1 fusion protein mediated by cell penetrated peptide PEP-1, also known as PEP-1-HO-1 fusion protein, and investigated its role in renal I/R injury in rats. Male Sprague-Dawley rats were subjected to 45 minutes of ischemia by occluding the bilateral renal arteries and 6 hours of reperfusion to prepare the model of renal I/R. Animals were randomized to receive PEP-1-HO-1 fusion protein or equal volume of physiologic saline 30 minutes before ischemia. Results. Administration of PEP-1-HO-1 fusion protein resulted in a significant increase in HO-1 expression. His-probe expression (1 part of the PEP-1-HO-1 fusion protein) was only observed in PEP-1-HO-1-treated animals. I/R caused renal dysfunction and increases in malondialdehyde level and cell apoptosis, and decreased superoxide dismutase activity. Treatment of PEP-1-HO-1 fusion protein reversed these changes. Furthermore, administration of PEP-1-HO-1 inhibited the I/R-induced increase in nuclear factor-kappa B activation. Conclusions. These findings suggest that transduction of PEP-1-HO-1 attenuates renal I/R injury in rats, which might be partly attributable to its antioxidant and antiapoptotic effects.