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Is Renalase a Novel Player in Catecholaminergic Signaling? The Mystery of the Catalytic Activity of an Intriguing New Flavoenzyme

Author(s): Sara Baroni, Mario Milani, Vittorio Pandini, Giulio Pavesi, David Horner and Alessandro Aliverti

Affiliation: Dipartimento di Bioscienze, Universita degli Studi di Milano, via Celoria 26, 20133 Milano, Italy.

Abstract:

Renalase is a flavoprotein recently discovered in humans, preferentially expressed in the proximal tubules of the kidney and secreted in blood and urine. It is highly conserved in vertebrates, with homologs identified in eukaryotic and prokaryotic organisms. Several genetic, epidemiological, clinical and experimental studies show that renalase plays a role in the modulation of the functions of the cardiovascular system, being particularly active in decreasing the catecholaminergic tone, in lowering blood pressure and in exerting a protective action against myocardial ischemic damage. Deficient renalase synthesis might be the cause of the high occurrence of hypertension and adverse cardiac events in kidney disease patients. Very recently, recombinant human renalase has been structurally and functionally characterized in vitro. Results show that it belongs to the p-hydroxybenzoate hydroxylase structural family of flavoenzymes, contains non-covalently bound FAD with redox features suggestive of a dehydrogenase activity, and is not a catecholamine-degrading enzyme, either through oxidase or NAD(P)H-dependent monooxygenase reactions. The biochemical data now available will hopefully provide the basis for a systematic and rational quest toward the identification of the reaction catalyzed by renalase and of the molecular mechanism of its physiological action, which in turn are expected to favor the development of novel therapeutic tools for the treatment of kidney and cardiovascular diseases.

Keywords: Chronic kidney disease, end-stage renal disease, blood pressure, myocardial ischemia, sympathetic nervous system, catecholamines, oxidoreductase, nicotinamide dinucleotides

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Article Details

VOLUME: 19
ISSUE: 14
Page: [2540 - 2551]
Pages: 12
DOI: 10.2174/1381612811319140005
Price: $58