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.

Is renalase a novel player in catecholaminergic signaling? The mystery of the catalytic activity of an intriguing new flavoenzyme / S. Baroni, M. Milani, V. Pandini, G. Pavesi, D. Horner, A. Aliverti. - In: CURRENT PHARMACEUTICAL DESIGN. - ISSN 1381-6128. - 19:14(2013 Apr), pp. 2540-2551. [10.2174/1381612811319140005]

Is renalase a novel player in catecholaminergic signaling? The mystery of the catalytic activity of an intriguing new flavoenzyme

S. Baroni;V. Pandini;G. Pavesi;D. Horner;A. Aliverti
2013-04

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.
Blood pressure; Catecholamines; Chronic kidney disease; End-stage renal disease; Myocardial ischemia; Nicotinamide dinucleotides; Oxidoreductase; Sympathetic nervous system
Settore BIO/10 - Biochimica
Settore BIO/09 - Fisiologia
Settore BIO/11 - Biologia Molecolare
Settore BIO/14 - Farmacologia
Article (author)
File in questo prodotto:
File Dimensione Formato  
Aliverti CPDFF-2012-03_preprint.pdf

accesso aperto

Descrizione: Full article with Figures
Tipologia: Pre-print (manoscritto inviato all'editore)
Dimensione 791.18 kB
Formato Adobe PDF
791.18 kB Adobe PDF Visualizza/Apri
Renalase Aliverti review 2013_CurrPharmDes.pdf

non disponibili

Descrizione: Articolo completo
Tipologia: Publisher's version/PDF
Dimensione 2.53 MB
Formato Adobe PDF
2.53 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/219511
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 22
  • ???jsp.display-item.citation.isi??? 20
social impact