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Renalase protects against ischemic AKI.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2013 Feb; Vol. 24 (3), pp. 445-55. Date of Electronic Publication: 2013 Feb 07. - Publication Year :
- 2013
-
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.
- Subjects :
- Acute Kidney Injury metabolism
Acute Kidney Injury pathology
Adrenergic alpha-Antagonists pharmacology
Animals
Apoptosis drug effects
Gene Expression drug effects
Humans
Inflammation Mediators metabolism
Ischemia metabolism
Ischemia pathology
Kidney Tubular Necrosis, Acute metabolism
Kidney Tubular Necrosis, Acute pathology
Kidney Tubular Necrosis, Acute prevention & control
Macrophages drug effects
Macrophages pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Monoamine Oxidase deficiency
Monoamine Oxidase genetics
Monoamine Oxidase metabolism
Neutrophil Infiltration drug effects
Norepinephrine blood
Phentolamine pharmacology
RNA, Messenger genetics
RNA, Messenger metabolism
Recombinant Proteins pharmacology
Reperfusion Injury metabolism
Reperfusion Injury pathology
Reperfusion Injury prevention & control
Acute Kidney Injury prevention & control
Ischemia prevention & control
Monoamine Oxidase pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1533-3450
- Volume :
- 24
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 23393318
- Full Text :
- https://doi.org/10.1681/ASN.2012090943