AUTHOR=Xiao Fengxia , Zimpelmann Joseph , Burger Dylan , Kennedy Christopher , Hébert Richard L. , Burns Kevin D. TITLE=Protein Kinase C-δ Mediates Shedding of Angiotensin-Converting Enzyme 2 from Proximal Tubular Cells JOURNAL=Frontiers in Pharmacology VOLUME=7 YEAR=2016 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2016.00146 DOI=10.3389/fphar.2016.00146 ISSN=1663-9812 ABSTRACT=
Angiotensin-converting enzyme 2 (ACE2) degrades angiotensin (Ang) II to Ang-(1–7), and protects against diabetic renal injury. Soluble ACE2 fragments are shed from the proximal tubule, and appear at high levels in the urine with diabetes. High glucose-induced shedding of ACE2 from proximal tubular cells is mediated by the enzyme “a disintegrin and metalloproteinase-17″ (ADAM17). Here, we investigated the mechanism for constitutive shedding of ACE2. Mouse proximal tubular cells were cultured and ACE2 shedding into the media was assessed by enzyme activity assay and immunoblot analysis. Cells were incubated with pharmacologic inhibitors, or transfected with silencing (si) RNA. Incubation of proximal tubular cells with increasing concentrations of