The role of renalase in catecholamine biosynthesis: a new protective mechanism against hypertension?

Abstract

Renalase is a secretory protein that may protect against hypertension by reducing levels of circulating catecholamines (CAs). Renalase knockout mice are hypertensive with elevated CA levels. There are no known physiological mechanisms that fully describe renalase’s influence on plasma CAs. The adrenal medulla is a major site for CA regulation, however, the role of renalase in this tissue has not been investigated. The purpose of this study was to determine a potential role of renalase in this tissue using three objectives: 1) Examine the regulation of renalase by signal activators of CA biosynthesis; 2) Determine the effects of renalase on the regulation of CA-biosynthesizing enzymes; 3) Examine the expression of renalase in hypertensive rats. For objective 1, renalase expression was analyzed in pheochromocytoma-derived PC12 cells after treatment with 10 signal activators (e.g. phorbol 12-myristate 13-acetate (PMA), forskolin, cobalt chloride (CoCl2), and dexamethasone (Dex)). For objective 2, PC12 cells were treated with recombinant renalase and mRNA levels of CA-biosynthesizing enzymes were quantitated. For objective 3, renalase expression was examined in adrenal glands from spontaneously hypertensive rats (SHRs) and compared with normotensive Wistar-Kyoto rats (WKYs). RT-PCR and western blotting were performed to quantify mRNA and protein levels. Three signal activators significantly altered renalase expression; changes in renalase expression were observed after PMA, CoCl2, and Dex treatment. Recombinant renalase treatment did not change the expression of CA-biosynthesizing enzymes. SHRs compared to WKYs had significantly higher levels of renalase mRNA, but not protein. Overall, this study is a first step to determine if renalase’s role in the adrenal medulla is to regulate CA biosynthesis and protect against hypertension.