STUDIES ON ANGIOTENSIN-(1-7) AND MITOCHONDRIA: THE ROLE OF AN INTRACELLULAR RENIN-ANGIOTENSIN SYSTEM WITHIN THE KIDNEY

Several therapies we have available to treat high blood pressure and the resulting kidney failure target a classic circulating hormonal system - the renin-angiotensin System (RAS), and specifically, the ACE-Ang II-AT1 receptor axis. We have focused strategically on investigating novel intracellular pathways by which Ang-(1-7) is generated and degraded since this alternative pathway within the kidney and other tissues may antagonize the Ang II-AT1 receptor mediated actions. We recently identified the presence of a novel enzyme activity in the brain that degrades Ang-(1-7) and is negatively correlated with central Ang-(1-7) levels and blood pressure. Moreover, seminal studies as a part of my graduate work identified this enzyme activity in the kidney, specifically in the proximal tubules and in a human proximal tubule cell line. Utilizing the human tubule cells, we purified and identified the Ang-(1-7) degrading activity as Dipeptidyl-Peptidase 3 (DPP 3). Given the bioactive role of Ang-(1-7) counteracting the deleterious effects of Ang II, we further established that the beneficial intracellular actions of Ang-(1-7) may reflect the mitochondria. Thus, we demonstrated that mitochondria isolated from sheep renal cortex expressed RAS components and contained the molecular machinery to produce Ang-(1-7) intracellularly within the kidney that include the endopeptidases neprilysin (NEP) and thimet oligopeptidase (TOP) that process Ang I directly to Ang-(1-7).

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2016

Author dc:creator

• Wilson, Bryan Anthony

• angiotensin-(1-7)

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/59269

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/59269