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

Abstract

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-κB 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.

• Authors: X-H He, J-J Tang, Y-L Wang, Z-Z Zhang, X-T Yan
• Journal: Transplantation proceedings (Transplant Proc) 2015 Jul-Aug Vol. 47 Issue 6 Pg. 1627-32 ISSN: 1873-2623 [Electronic] United States
• PMID: 26293025 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• NF-kappa B
• Recombinant Fusion Proteins
• Malondialdehyde
• Heme Oxygenase (Decyclizing)
• Heme Oxygenase-1
• PEP-1-heme oxygenase-1 fusion protein

Topics

• Animals
• Antioxidants (metabolism)
• Apoptosis (drug effects)
• Disease Models, Animal
• Heme Oxygenase (Decyclizing) (metabolism)
• Heme Oxygenase-1 (metabolism, pharmacology)
• Ischemic Preconditioning (methods)
• Kidney (blood supply, metabolism)
• Male
• Malondialdehyde (metabolism)
• NF-kappa B (metabolism)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Recombinant Fusion Proteins (metabolism, pharmacology)
• Reperfusion Injury (metabolism)