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Expression of an angiotensin‐(1‐7) endopeptidase in proximal tubules of the sheep and human kidney (1088.10)
Author(s) -
Wilson Bryan,
Marshall Allyson,
Pirro Nancy,
Su Yixin,
Rose James,
Chappell Mark
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1088.10
Subject(s) - neprilysin , endopeptidase , renin–angiotensin system , medicine , chemistry , kidney , endocrinology , angiotensin ii , angiotensin iii , prolyl endopeptidase , enzyme , angiotensin ii receptor type 1 , biology , biochemistry , receptor , blood pressure
Angiotensin‐(1‐7) [Ang 7] is a an active peptide of the renin‐angiotensin system (RAS) that generally antagonizes the actions of Ang II. Within the kidney, Ang 7 is derived from Ang I by endopeptidases including neprilysin (NEP) and thimet oligopeptidase (TOP) or from Ang II by the carboxypeptidase ACE2. Ang 7 is primarily degraded by ACE to the Ang‐(1‐5) in the circulation and tissues; however, we identified an endopeptidase in sheep CSF that efficiently degraded Ang 7 to Ang‐(1‐4) (Ang 4) and accounted for the majority of Ang 7 metabolism in this compartment (Marshall et al AJP 2013). The current study determined whether the Ang 7 peptidase is expressed in the kidney, specifically in isolated proximal tubules of the sheep and human renal epithelial cells. Activity was determined by the conversion of 125I‐Ang 7 to 125I‐Ang 4 in a 100,000 xg supernatant fraction. Both the sheep proximal tubules and the human epithelial cells expressed Ang 7 endopeptidase activity. Kinetic analysis revealed an apparent Km of 2.0 ± 1.0 µM and apparent Vmax’ of 93 ± 37 pmol/min/mg protein [n=3]. Peptidase activity in the isolated tubules was attenuated by the metalloendopeptidase inhibitor JMV‐390 with an IC50 of 0.81 ± 0.12 nM [n=3] that is ~50‐fold more potent than that of NEP and TOP. We conclude that an Ang 7 endopeptidase may be a novel component of the intrarenal RAS to regulate the tubular expression of Ang 7. Grant Funding Source : Supported by NIH grants HL56973, HL52972, HL112237, and HD047584