Renalase contributes to the renal protection of delayed ischaemic preconditioning via the regulation of hypoxia-inducible factor-1α.

Abstract

Ischaemic preconditioning (IPC) attenuates acute kidney injury (AKI) from renal ischaemia reperfusion. Renalase, an amine oxidase secreted by the proximal tubule, not only degrades circulating catecholamines but also protects against renal ischaemia reperfusion injury. Here, it has been suggested that the renoprotective effect of renal IPC is partly mediated by renalase. In a model of brief intermittent renal IPC, the increased cortex renalase expression was found to last for 48 hrs. IPC significantly reduced renal tubular inflammation, necrosis and oxidative stress following renal ischaemia reperfusion injury. Such effects were attenuated by blocking renalase with an anti-renalase monoclonal antibody. We further demonstrated that renalase expression was up-regulated by hypoxia in vitro via an hypoxia-inducible factor (HIF)-1α mechanism. The IPC-induced up-regulation of renalase in vivo was also reduced by pre-treatment with an HIF-1α inhibitor, 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole. In summary, the renoprotective effect of IPC is partly dependent on the renalase expression, which may be triggered by hypoxia via an HIF-1α mechanism. Endogenous renalase shows potential as a therapeutic agent for the prevention and treatment of AKI.

• Authors: Feng Wang, Guangyuan Zhang, Tao Xing, Zeyuan Lu, Junhui Li, Cheng Peng, Guohua Liu, Niansong Wang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 19 Issue 6 Pg. 1400-9 (Jun 2015) ISSN: 1582-4934 [Electronic] England
• PMID: 25781495 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Hypoxia-Inducible Factor 1, alpha Subunit
• Protective Agents
• Monoamine Oxidase
• renalase

Topics

• Animals
• Blotting, Western
• Cell Hypoxia
• Cell Line
• Gene Expression Regulation, Enzymologic
• Humans
• Hypoxia
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Ischemic Preconditioning
• Kidney (blood supply, enzymology, metabolism)
• Male
• Monoamine Oxidase (genetics, metabolism)
• Protective Agents (metabolism)
• Rats, Sprague-Dawley
• Reperfusion Injury (genetics, metabolism, prevention & control)
• Reverse Transcriptase Polymerase Chain Reaction
• Up-Regulation