Cathelicidin PR-39 peptide inhibits hypoxia/reperfusion-induced kidney cell apoptosis by suppression of the endoplasmic reticulum-stress pathway.

Abstract

Ischemia/reperfusion injury (IRI) is a major cause of acute kidney damage, which often occurs in deceased donor kidney transplants. Cathelicidin PR-39 peptide possesses anti-inflammatory and wound repair effects through tissue angiogenesis and anti-apoptosis. This study assessed the role of PR-39 in anti-apoptosis in vitro using a lentiviral vector with a kidney specific promoter (KSP) to drive PR-39 expression. Our data revealed that PR-39 peptide was specifically over-expressed in kidney-derived HK-2 cells, but was scarcely detected in non-kidney tissue-derived cells. PR-39 over-expression had a protective role in the hypoxia/re-oxygenation (H/R) treated cells. The anti-apoptotic activity of PR-39 peptide was mediated by the inhibition of caspase-2, caspase-12 and caspase-3 activity in the endoplasmic reticulum (ER) stress-induced apoptotic pathway. It was also revealed that the anti-apoptotic effect of PR-39 peptide was mediated by an apoptosis-related protein, cellular inhibitor apoptosis protein-2 (c-IAP-2). Taken together, the current data demonstrate that PR-39 expression driven by KSP could prevent kidney damage (apoptosis) from IRI via the ER stress-induced apoptotic pathway.

• Authors: Jing Liu, Wujun Xue, Heli Xiang, Jin Zheng, Yanlong Zhao, Lizi Jiao, Zizhao Jiao
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 48 Issue 8 Pg. 714-22 (Aug 2016) ISSN: 1745-7270 [Electronic] China
• PMID: 27353320 (Publication Type: Journal Article)
• Copyright: © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Cathelicidins

Topics

• Animals
• Apoptosis (drug effects)
• Cathelicidins (pharmacology)
• Endoplasmic Reticulum Stress (drug effects)
• Flow Cytometry
• Human Umbilical Vein Endothelial Cells
• Humans
• Hypoxia (prevention & control)
• Kidney (pathology)
• Mice
• NIH 3T3 Cells
• Reperfusion Injury (pathology, prevention & control)