Abstract
Elevated levels of plasma catecholamines accompany ischemic AKI, possibly contributing the inflammatory response. Renalase, an amine oxidase secreted by the proximal tubule, degrades circulating catecholamines and reduces myocardial necrosis, suggesting that it may protect against renal ischemia reperfusion injury. Here, mice subjected to renal ischemia reperfusion injury had significantly lower levels of renalase in the plasma and kidney compared with sham-operated mice. Consistent with this, plasma NE levels increased significantly after renal ischemia reperfusion injury. Furthermore, renal tubular inflammation, necrosis, and apoptosis were more severe and plasma catecholamine levels were higher in renalase-deficient mice subjected to renal ischemia reperfusion compared with wild-type mice. Administration of recombinant human renalase reduced plasma catecholamine levels and ameliorated ischemic AKI in wild-type mice. Taken together, these data suggest that renalase protects against ischemic AKI by reducing renal tubular necrosis, apoptosis, and inflammation, and that plasma renalase might be a biomarker for AKI. Recombinant renalase therapy may have potential for the prevention and treatment of AKI.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Kidney Injury / metabolism
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Acute Kidney Injury / pathology
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Acute Kidney Injury / prevention & control*
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Adrenergic alpha-Antagonists / pharmacology
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Animals
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Apoptosis / drug effects
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Gene Expression / drug effects
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Humans
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Inflammation Mediators / metabolism
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Ischemia / metabolism
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Ischemia / pathology
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Ischemia / prevention & control*
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Kidney Tubular Necrosis, Acute / metabolism
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Kidney Tubular Necrosis, Acute / pathology
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Kidney Tubular Necrosis, Acute / prevention & control
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Macrophages / drug effects
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Macrophages / pathology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Monoamine Oxidase / deficiency
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Monoamine Oxidase / genetics
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Monoamine Oxidase / metabolism
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Monoamine Oxidase / pharmacology*
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Neutrophil Infiltration / drug effects
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Norepinephrine / blood
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Phentolamine / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Recombinant Proteins / pharmacology
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Reperfusion Injury / metabolism
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Reperfusion Injury / pathology
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Reperfusion Injury / prevention & control
Substances
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Adrenergic alpha-Antagonists
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Inflammation Mediators
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RNA, Messenger
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Recombinant Proteins
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Monoamine Oxidase
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renalase
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Norepinephrine
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Phentolamine