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

Autor: V. I. Fedchenko, Alexei Medvedev, Alexander V. Veselovsky, I. S. Severina
Rok vydání: 2015
Předmět:
Zdroj: Biomeditsinskaya Khimiya. 61:667-679
ISSN: 2310-6905
2310-6972
DOI: 10.18097/pbmc20156106667
Popis: 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, its possible contribution to the antihypertensive effect of renalase remains unclear. Thus, the antihypertensive effect of renalase still remains a phenomenon with unclear biochemical mechanim(s) and functions of intracellular and extracellular (circulating) renalases obviously differ.Renalaza – nedavno obnaruzhennyĭ belok, kotoromu otvodiat vazhnuiu (khotia i ne ochen' poniatnuiu na segodniashniĭ den') rol' v reguliatsii arterial'nogo davleniia. V dannom obzore summirovany sobstvennye i literaturnye dannye, nakoplennye so vremeni pervoĭ publikatsii (2005 g.) o strukturnykh i vozmozhnykh kataliticheskikh svoĭstvakh renalazy. Pervonachal'nye dannye ob FAD-zavisimoĭ aminoksidaznoĭ aktivnosti, ne byli podtverzhdeny v nezavisimykh éksperimentakh v drugikh laboratoriiakh. K tomu zhe dlia predpolagaemoĭ aminoksidaznoĭ aktivnosti renalazy krovi neobkhodim flavinovogo kofaktor, prisutstvie kotorogo u tsirkuliruiushcheĭ v krovi renalazy do sikh ne bylo obnaruzheno. Bolee togo, ékskretiruemaia v mochu renalaza lishena N-peptida, bez kotorogo sviazyvanie FAD nevozmozhno. Dannye gruppy Aliverti o sviazyvanii renalazoĭ NAD(P)H i proiavlenii étim fermentom diaforaznoĭ aktivnosti, stimulirovalo issledovaniia renalazy kak NAD(P)H-oksidazy, kotoraia kataliziruet reaktsiiu sookisleniia katekholaminov. Odnako fiziologicheskie znachenie takogo roda vnekletochnoĭ katekholamin- metaboliziruiushcheĭ aktivnosti neiasno, esli priniat' vo vnimanie sushchestvovanie gorazdo bolee éffektivnykh sistem (takikh kak NAD(P)H-oksidaza neĭtrofilov, ksantinoksidaza/ksantin) v sisteme tsirkuliatsii, sposobnykh osushchestvliat' reaktsii sookisleniia. Nedavno opisana a-NAD(P)H-oksidaznaia/anomeraznaia aktivnost' étogo belka, kotoraia takzhe sposobstvuet okislitel'nomu prevrashcheniiu izomerov b-NADH, okazyvaiushchikh ingibitornoe deĭstvie na aktivnost' vnutrikletochnykh NAD-zavisimykh degidrogenaz. Odnako i ee vozmozhnyĭ vklad v antigipertenzivnuiu aktivnost' renalazy neponiaten. Takim obrazom, ne vyzyvaiushchaia somneniia antigipertenzivnaia aktivnost' étogo belka do sikh por ostaetsia fenomenom s neiasnym biokhimicheskim mekhanizmom, a funktsii vnutrikletochnoĭ i tsirkuliruiushcheĭ v krovi renalaz, po-vidimomu, razlichaiutsia.
Databáze: OpenAIRE
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