2026-09-22T09:32:33Zhttps://wakespace.lib.wfu.edu/server/oai/request

oai:null:10339/592692026-09-02T15:20:00Zcom_10339_14934col_10339_38132

Wilson, Bryan Anthony 2016-05-21T08:35:34Z 2016-05-21T08:35:34Z 2016 https://wakespace.lib.wfu.edu/handle/10339/59269 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). en Wake Forest University angiotensin-(1-7) intracellular kidney mitochondria proximal tubules renin-angiotensin system STUDIES ON ANGIOTENSIN-(1-7) AND MITOCHONDRIA: THE ROLE OF AN INTRACELLULAR RENIN-ANGIOTENSIN SYSTEM WITHIN THE KIDNEY Dissertation Chappell, Mark C Rose, James C Taylor, Robert N Brosnihan, K Bridget Molecular Medicine and Translational Science open.access