Multiple roles of renalase.
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Abstract
Renalase (RNLS) is a small flavoprotein produced mainly by the kidney. The latest investigations show, that RNLS might be an "organolase” as the RNLS gene is expressed in many other cells and tissues, including the nervous system, endocrinal and digestive tract organs, lungs, or heart in humans and some other mammals [1]. RNLS shows both intracellular and extracellular activity. Intracellular RNLS acts as an enzyme that in the presence of FAD cofactor oxidizes 2- and 6- DHNAD(P) to β-NAD(P)H, which is its biologically active form. This action prevents toxicity resulting from inhibition of many βNAD(P)H-dependent enzymes and reactions. In turn, extracellular renalase, as well as RP-200 and RP-220 peptides which are fragments of the protein, activate some of the signaling pathways, including Akt and MAP kinases, and therefore promoting cell survival. This activity is mediated by binding of renalase to its recently discovered receptor – plasma membrane Ca2+-ATPase-4b (PMCA4b), which is the main form of this pump in erythrocytes, cells that are involved in renalase transport.
