ArticleAmerican journal of physiology. Cell physiology2013
Identification of prolyl carboxypeptidase as an alternative enzyme for processing of renal angiotensin II using mass spectrometry.
Article in American journal of physiology. Cell physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
- Upregulation of angiotensin-(1-7) formation in human podocytes - enzyme activity assay upon fluid flow shear stress.PloS one · 2026Article
- Progress in monitoring molecular, cellular and metabolic dynamics using mass spectrometry imaging.Bioanalysis · 2025Review
- Clinical Relevance of Plasma Prolylcarboxypeptidase Level in Patients with Idiopathic Acute Optic Neuritis.Journal of clinical medicine · 2024Article
- The Serum ACE2, CTSL, AngII, and TNFα Levels after COVID-19 and mRNA Vaccines: The Molecular Basis.Biomedicines · 2023Article
- C1 inhibitor and prolylcarboxypeptidase modulate prekallikrein activation on endothelial cells.The Journal of allergy and clinical immunology · 2023Article
- Rethinking the Role of the Renin-Angiotensin System in the Pandemic Era of SARS-CoV-2.Journal of cardiovascular development and disease · 2023Article
- COVID-19, vaccines and deficiency of ACEEuropean journal of internal medicine · 2022Review
- Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting.Pharmacological reviews · 2022Review
- Classical and Counter-Regulatory Renin-Angiotensin System: Potential Key Roles in COVID-19 Pathophysiology.CJC open · 2021Review
- A comprehensive insight into the role of zinc deficiency in the renin-angiotensin and kinin-kallikrein system dysfunctions in COVID-19 patients.Saudi journal of biological sciences · 2021Review
- Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review.The review of diabetic studies : RDS · 2021Review
- Role of the renin-angiotensin system in the development of severe COVID-19 in hypertensive patients.American journal of physiology. Lung cellular and molecular physiology · 2020Review
- Ang II (Angiotensin II) Conversion to Angiotensin-(1-7) in the Circulation Is POP (Prolyloligopeptidase)-Dependent and ACE2 (Angiotensin-Converting Enzyme 2)-Independent.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Understanding the Pathophysiology of COVID-19: Could the Contact System Be the Key?Frontiers in immunology · 2020Article
- Application of System Biology to Explore the Association of Neprilysin, Angiotensin-Converting Enzyme 2 (ACE2), and Carbonic Anhydrase (CA) in Pathogenesis of SARS-CoV-2.Biological procedures online · 2020Article
- Deficiency of the Angiotensinase Aminopeptidase A Increases Susceptibility to Glomerular Injury.Journal of the American Society of Nephrology : JASN · 2017Article
- Prolylcarboxypeptidase deficiency is associated with increased blood pressure, glomerular lesions, and cardiac dysfunction independent of altered circulating and cardiac angiotensin II.Journal of molecular medicine (Berlin, Germany) · 2017Article
- A Fluorometric Method of Measuring Carboxypeptidase Activities for Angiotensin II and Apelin-13.Scientific reports · 2017Article
- Neprilysin is a Mediator of Alternative Renin-Angiotensin-System Activation in the Murine and Human Kidney.Scientific reports · 2016Article
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8 authors at 3 institutions in 1 country.
Funding
Abstract
Angiotensin-converting enzyme 2 (ACE2) catalyzes conversion of ANG II to ANG-(1-7). The present study uses newly established proteomic approaches and genetic mouse models to examine the contribution of alternative renal peptidases to ACE2-independent formation of ANG-(1-7). In situ and in vitro mass spectrometric characterization showed that substrate concentration and pH control renal ANG II processing. At pH ≥6, ANG-(1-7) formation was significantly reduced in ACE2 knockout (KO) mice. However, at pH <6, formation of ANG-(1-7) in ACE2 KO mice was similar to that in wild-type (WT) mice, suggesting alternative peptidases for renal ANG II processing. Furthermore, the dual prolyl carboxypeptidase (PCP)-prolyl endopeptidase (PEP) inhibitor Z-prolyl-prolinal reduced ANG-(1-7) formation in ACE2 KO mice, while the ACE2 inhibitor MLN-4760 had no effect. Unlike the ACE2 KO mice, ANG-(1-7) formation from ANG II in PEP KO mice was not different from that in WT mice at any tested pH. However, at pH 5, this reaction was significantly reduced in kidneys and urine of PCP-depleted mice. In conclusion, results suggest that ACE2 metabolizes ANG II in the kidney at neutral and basic pH, while PCP catalyzes the same reaction at acidic pH. This is the first report demonstrating that renal ANG-(1-7) formation from ANG II is independent of ACE2. Elucidation of ACE2-independent ANG-(1-7) production pathways may have clinically important implications in patients with metabolic and renal disease.
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