Dipeptidyl peptidase 3 modulates the renin-angiotensin-aldosterone system

Shalinee Jha, Ulrike Taschler, Oliver Domenig, Marko Poglitsch, Benjamin Bourgeois, Marion Pollheimer, Tobias Madl, Karl Gruber, Robert Zimmermann, Peter Macheroux

Research output: Contribution to conferencePoster

Abstract

Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase involved in degrading oligopeptides with 4–12 amino acid residues. It has been associated with several pathophysiological processes, including blood pressure regulation, pain signaling and cancer cell defense against oxidative stress. However, the physiological substrates and the cellular pathways that are potentially targeted by DPP3 to mediate these effects remain unknown. Here, we show that global DPP3-deficiency in mice (DPP3-/-) affects the renin-angiotensin system (RAS). LC-MS based profiling of circulating angiotensin peptides revealed elevated levels of angiotensin II, III, IV, and 1-5, while mean arterial blood pressure, renin activity and aldosterone levels remained unchanged. Activity assays using the purified enzyme confirmed that angiotensin peptides are substrates for DPP3. Aberrant angiotensin signaling was associated with a substantial higher water intake and increased renal reactive oxygen species (ROS) formation in DPP3-/- mice. Taken together, our observations suggest that DPP3 regulates the RAS pathway and water homeostasis by degrading circulating angiotensin peptides.
Original languageEnglish
Publication statusPublished - 9 Feb 2020
EventGordon Research Conference on Angiotensin: The RAAS: Integrating Novel Technologies, Clinical Studies and Personalized Therapeutics to Preserve Health - Renaissance Tuscany Il Ciocco, Via Giovanni Pascoli, Lucca (Barga), Italy
Duration: 9 Feb 202014 Feb 2020
https://www.grc.org/angiotensin-conference/2020/

Conference

ConferenceGordon Research Conference on Angiotensin
Abbreviated titleGRC- Angiotensin
CountryItaly
CityLucca (Barga)
Period9/02/2014/02/20
Internet address

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fields of Expertise

  • Human- & Biotechnology

Cooperations

  • BioTechMed-Graz
  • NAWI Graz

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