Remote ischemic preconditioning for kidney protection: GSK3β-centric insights into the mechanism of action.

Abstract

Preventing acute kidney injury (AKI) in high-risk patients following medical interventions is a paramount challenge for clinical practice. Recent data from animal experiments and clinical trials indicate that remote ischemic preconditioning, represented by limb ischemic preconditioning, confers a protective action on the kidney. Ischemic preconditioning is effective in reducing the risk for AKI following cardiovascular interventions and the use of iodinated radiocontrast media. Nevertheless, the underlying mechanisms for this protective effect are elusive. A protective signal is conveyed from the remote site undergoing ischemic preconditioning, such as the limb, to target organs, such as the kidney, by multiple potential communication pathways, which may involve humoral, neuronal, and systemic mechanisms. Diverse transmitting pathways trigger a variety of signaling cascades, including the reperfusion injury salvage kinase and survivor activating factor enhancement pathways, all of which converge on glycogen synthase kinase 3β (GSK3β). Inhibition of GSK3β subsequent to ischemic preconditioning reinforces the Nrf2-mediated antioxidant defense, diminishes the nuclear factor-κB-dependent proinflammatory response, and exerts prosurvival effects ensuing from the desensitized mitochondria permeability transition. Thus, therapeutic targeting of GSK3β by ischemic preconditioning or by pharmacologic preconditioning with existing US Food and Drug Administration-approved drugs having GSK3β-inhibitory activities might represent a pragmatic and cost-effective adjuvant strategy for kidney protection and prophylaxis against AKI.

• Authors: Zhangsuo Liu, Rujun Gong
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 66 Issue 5 Pg. 846-56 (Nov 2015) ISSN: 1523-6838 [Electronic] United States
• PMID: 26271146 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• NF-E2-Related Factor 2
• NF-kappa B
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3

Topics

• Acute Kidney Injury (metabolism, prevention & control)
• Animals
• Extremities (blood supply)
• Glycogen Synthase Kinase 3 (antagonists & inhibitors, metabolism)
• Glycogen Synthase Kinase 3 beta
• Humans
• Ischemia (metabolism)
• Ischemic Preconditioning (methods)
• Kidney (blood supply)
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Reperfusion Injury (metabolism, prevention & control)
• Signal Transduction