Aminopeptidase N reduces basolateral Na+-K+-ATPase in proximal tubule cells

Aminopeptidase N/CD13 (Anpep) is a membrane-bound protein that catalyzes the formation of natriuretic hexapeptide angiotensin IV (ANG IV) from ANG III. We previously reported that Anpep is more highly expressed in the kidneys of Dahl salt-resistant (SR/Jr) than salt-sensitive (SS/Jr) rats, Anpep maps to a quantitative trait locus for hypertension, and that the Dahl SR/Jr rat contains a functional polymorphism of the gene. This suggests that renal Anpep may be linked to salt sensitivity; however, its effect on renal Na handling has not been determined. Here, we examined regulation of basolateral Na+-K+-ATPase, a preeminent basolateral Na+ transporter in proximal tubule cells, by Anpep in LLC-PK1 cells. Treatment of the cells with Anpep siRNA increased total cellular Na+-K+-ATPase activity and basolateral Na+-K+-ATPase abundance by approximately twofold. Conversely, Anpep overexpression reduced Na+-K+-ATPase activity and basolateral abundance by ∼50%. Similar effects were observed after treatment with ANG I...