Premium
Discovery of new renal Ang II processing enzyme activity using mass spectrometry and gene deletion mouse models
Author(s) -
Grobe Nadja,
Elased Khalid M,
Salem Esam SB,
Gurley Susan B,
Ong Frank S,
Bernstein Kenneth E,
Schmaier Alvin H,
Morris Mariana
Publication year - 2013
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.27.1_supplement.1165.18
Subject(s) - kidney , chemistry , prolyl endopeptidase , enzyme , angiotensin ii , renin–angiotensin system , endocrinology , medicine , angiotensin converting enzyme 2 , renal cortex , biochemistry , biology , receptor , blood pressure , disease , covid-19 , infectious disease (medical specialty)
Angiotensin (Ang) converting enzyme 2 (ACE2) is expressed in the kidney and exerts its renoprotection via conversion of the vasoconstrictor Ang II to the vasodilator Ang‐(1–7). To better characterize the tissue distribution and activity of enzymes involved in Ang II processing novel in situ and in vitro mass spectrometric methods were used. Mouse kidney sections (12 μm) or kidney homogenates (20 μg protein) were incubated with 0.1–10 nmol Ang II at pH 4–10 for 5–30 min at 37 ºC. Ang (1–7) was predominantly formed in renal cortex and dependent on amount of Ang II and pH. Further, the contribution of alternative renal peptidases to ACE2 independent formation of Ang‐(1–7) was explored using gene deletion mouse models deficient of ACE2, prolyl carboxypeptidase (PCP) or prolyl endopeptidase. Results suggest that ACE2 processes renal Ang II under neutral and basic conditions (pH>;6), while PCP catalyzes this reaction at acidic pH (pH<6). Using type 1 and type 2 diabetic animals, renal ACE2 was increased while renal PCP was decreased. This is the first report to demonstrate that renal Ang II processing to Ang‐(1–7) is independent of ACE2. Elucidation of renal Ang II processing pathways should be clinically important in patients with metabolic and renal disease.