The history of renalase from amine oxidase to alpha-NAD(P)H-oxidase/anomerase

Severina I.S.1, Fedchenko V.I.1, Veselovsky A.V.1, Medvedev A.E.1

1. Institute of Biomedical Chemistry, Moscow, Russia
Section: Review
DOI: 10.18097/PBMC20156106667      PubMed Id: 26716738
Year: 2015  Volume: 61  Issue: 6  Pages: 667-679
Renalase is a recently discovered secretory protein, which plays a certain (still poorly understood) role in regulation of blood pressure. The review summarizes own and literature data accumulated since the first publication on relanase (2005). Initial reports on FAD-dependent amine oxidase activity of this protein were not confirmed in independent experiments performed in different laboratories. In addition, proposed amine oxidase activity of circulating extracellular renalase requires the presence of FAD, which has not been detected either in blood or urinary renalase. Moreover, renalase excreted into urine lacks its N-terminal peptide, which is ultimately needed for accommodation of the FAD cofactor. Results of the Aliverti’s group on NAD(P)H binding by renalase and weak diaphorase activity of this protein stimulated further studies of renalase as NAD(P)H oxidase catalyzing reaction of catecholamine co-oxidation. However, physiological importance of such extracellular catecholamine-metabolizing activity (demonstrated in one laboratory and not detected in another laboratory) remains unclear due to existence of much more active enzymatic systems (e.g. neutrophil NAD(P)H oxidase, xanthine oxidase/xanthine) in circulation, which can perform such co-oxidation reactions. Recently a-NAD(P)H oxidase/anomerase activity of renalase, which also pomotes oxidative conversion of b-NADH isomers inhibiting activity of NAD-dependent dehydrogenases, has been described. However, itspossible contribution tothe antihypertensive effect ofrenalase remains unclear. Thus, theantihypertensive effect of renalase still remains a phenomenon with unclear biochemical mechanim(s) and functions of intracellular and extracellular (circulating) renalases obviously differ.
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Keywords: renalase, N-terminal peptide, FAD-binding domain, catalytic functions, antihypertensive effect

Severina, I. S., Fedchenko, V. I., Veselovsky, A. V., Medvedev, A. E. (2015). The history of renalase from amine oxidase to alpha-NAD(P)H-oxidase/anomerase. Biomeditsinskaya Khimiya, 61(6), 667-679.
This paper is also available as the English translation: 10.1134/S1990750816020098
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