Abstract
The mortality rate from acute kidney injury after major cardiovascular operations can be as high as 60%, and no therapies have been proved to prevent acute kidney injury in this setting. Here, we show that preconditioning with the anesthetic gas xenon activates hypoxia-inducible factor 1alpha (HIF-1alpha) and its downstream effectors erythropoietin and vascular endothelial growth factor in a time-dependent manner in the kidneys of adult mice. Xenon increased the efficiency of HIF-1alpha translation via modulation of the mammalian target of rapamycin pathway. In a model of renal ischemia-reperfusion injury, xenon provided morphologic and functional renoprotection; hydrodynamic injection of HIF-1alpha small interfering RNA demonstrated that this protection is HIF-1alpha dependent. These results suggest that xenon preconditioning is a natural inducer of HIF-1alpha and that administration of xenon before renal ischemia can prevent acute renal failure. If these data are confirmed in the clinical setting, then preconditioning with xenon may be beneficial before procedures that temporarily interrupt renal perfusion.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anesthetics / administration & dosage
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Animals
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Basic Helix-Loop-Helix Transcription Factors / drug effects
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Basic Helix-Loop-Helix Transcription Factors / genetics*
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Basic Helix-Loop-Helix Transcription Factors / physiology*
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Carrier Proteins / genetics
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Cells, Cultured
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Erythropoietin / genetics
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Gene Expression Regulation / drug effects
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Humans
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Ischemic Preconditioning / methods*
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Kidney / drug effects
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Kidney / physiology*
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Kidney / physiopathology
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Mice
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Mice, Inbred C57BL
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Protein Biosynthesis / drug effects
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Protein Subunits / metabolism
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RNA, Messenger / genetics
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Reperfusion Injury / physiopathology
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Reperfusion Injury / prevention & control*
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TOR Serine-Threonine Kinases
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Transcription, Genetic
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Ubiquitin / metabolism
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Vascular Endothelial Growth Factor A / genetics
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Xenon / administration & dosage
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Xenon / therapeutic use*
Substances
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Anesthetics
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Basic Helix-Loop-Helix Transcription Factors
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Carrier Proteins
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Protein Subunits
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RNA, Messenger
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Ubiquitin
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Vascular Endothelial Growth Factor A
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Erythropoietin
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endothelial PAS domain-containing protein 1
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Xenon
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Phosphotransferases (Alcohol Group Acceptor)
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MTOR protein, human
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mTOR protein, mouse
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TOR Serine-Threonine Kinases