Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Discovery of O-glycans on atrial natriuretic peptide (ANP) that affect both its proteolytic degradation and potency at its cognate receptor

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Vagal afferent cholecystokinin receptor activation is required for glucagon-like peptide-1-induced satiation

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Coagulation parameters in the newborn and infant - the Copenhagen Baby Heart and COMPARE studies

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Entero-pancreatic hormone secretion, gastric emptying, and glucose absorption after frequently sampled meal tests

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Copeptin and renal function decline, cardiovascular events and mortality in type 1 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Combinatorial, additive and dose-dependent drug–microbiome associations

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Lasse H Hansen
  • Thomas Daugbjerg Madsen
  • Christoffer K Goth
  • Henrik Clausen
  • Yang Chen
  • Nina Dzhoyashvili
  • Seethalakshmi R Iyer
  • S Jeson Sangaralingham
  • John C Burnett
  • Jens F Rehfeld
  • Sergey Y Vakhrushev
  • Katrine T Schjoldager
  • Jens P Goetze
View graph of relations

Atrial natriuretic peptide (ANP) is a peptide hormone that in response to atrial stretch is secreted from atrial myocytes into the circulation, where it stimulates vasodilatation and natriuresis. ANP is an important biomarker of heart failure where low plasma concentrations exclude cardiac dysfunction. ANP is a member of the natriuretic peptide (NP) family, which also includes the B-type natriuretic peptide (BNP) and the C-type natriuretic peptide. The proforms of these hormones undergo processing to mature peptides, and for proBNP, this process has previously been demonstrated to be regulated by O-glycosylation. It has been suggested that proANP also may undergo post-translational modifications. Here, we conducted a targeted O-glycoproteomics approach to characterize O-glycans on NPs and demonstrate that all NP members can carry O-glycans. We identified four O-glycosites in proANP in the porcine heart, and surprisingly, two of these were located on the mature bioactive ANP itself. We found that one of these glycans is located within a conserved sequence motif of the receptor-binding region, suggesting that O-glycans may serve a function beyond intracellular processing and maturation. We also identified an O-glycoform of proANP naturally occurring in human circulation. We demonstrated that site-specific O-glycosylation shields bioactive ANP from proteolytic degradation and modifies potency at its cognate receptor in vitro Furthermore, we showed that ANP O-glycosylation attenuates acute renal and cardiovascular ANP actions in vivo The discovery of novel glycosylated ANP proteoforms reported here significantly improves our understanding of cardiac endocrinology and provides important insight into the etiology of heart failure.

Original languageEnglish
JournalJournal of Biological Chemistry
Volume294
Issue number34
Pages (from-to)12567-12578
Number of pages12
ISSN0021-9258
DOIs
Publication statusPublished - 1 Jan 2019

ID: 58227587