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J Nutr Biochem. 2014 Nov;25(11):1226-34. doi: 10.1016/j.jnutbio.2014.05.013. Epub 2014 Jul 4.

Quercetin attenuates renal ischemia/reperfusion injury via an activation of AMP-activated protein kinase-regulated autophagy pathway.

Author information

  • 1Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 2Department of Urology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 3Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 4Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Integrated Diagnostics and Therapeutics, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan. Electronic address: ckchiang@ntu.edu.tw.
  • 5Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan. Electronic address: shinghwaliu@ntu.edu.tw.

Abstract

Renal ischemia/reperfusion (I/R) is a major cause of acute renal failure. Quercetin, a flavonoid antioxidant, presents in many kinds of food. The molecular mechanism of quercetin on renal protection during I/R is still unclear. Here, we investigated the role of AMP-activated protein kinase (AMPK)-regulated autophagy in renal protection by quercetin. To investigate whether quercetin protects renal cells from I/R-induced cell injury, an in vitro model of I/R and an in vivo I/R model were used. Cell apoptosis was determined by propidium iodide/annexin V staining. Western blotting and immunofluorescence were used to determine the autophagy. AMPK expression was inhibited with appropriate short hairpin RNA (shRNA). In cultured renal tubular cell I/R model, quercetin decreased the cell injury, up-regulated the AMPK phosphorylation, down-regulated the mammalian target of rapamycin (mTOR) phosphorylation and activated autophagy during I/R. Knockdown of AMPK by shRNA transfection decreased the quercetin-induced autophagy but did not affect the mTOR phosphorylation. In I/R mouse model, quercetin decreased the increased serum creatinine level and altered renal histological score. Quercetin also increased AMPK phosphorylation, inhibited the mTOR phosphorylation and activated autophagy in the kidneys of I/R mice. These results suggest that quercetin activates an AMPK-regulated autophagy signaling pathway, which offers a protective effect in renal I/R injury.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

AMPK; Apoptosis; Autophagy; Quercetin; Renal ischemia/reperfusion injury

[PubMed - indexed for MEDLINE]
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