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

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Hansen, LH, Madsen, TD, Goth, CK, Clausen, H, Chen, Y, Dzhoyashvili, N, Iyer, SR, Sangaralingham, SJ, Burnett, JC, Rehfeld, JF, Vakhrushev, SY, Schjoldager, KT & Goetze, JP 2019, 'Discovery of O-glycans on atrial natriuretic peptide (ANP) that affect both its proteolytic degradation and potency at its cognate receptor' The journal of biological chemistry, bind 294, nr. 34, s. 12567-12578. https://doi.org/10.1074/jbc.RA119.008102

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Hansen, Lasse H ; Madsen, Thomas Daugbjerg ; Goth, Christoffer K ; Clausen, Henrik ; Chen, Yang ; Dzhoyashvili, Nina ; Iyer, Seethalakshmi R ; Sangaralingham, S Jeson ; Burnett, John C ; Rehfeld, Jens F ; Vakhrushev, Sergey Y ; Schjoldager, Katrine T ; Goetze, Jens P. / Discovery of O-glycans on atrial natriuretic peptide (ANP) that affect both its proteolytic degradation and potency at its cognate receptor. I: The journal of biological chemistry. 2019 ; Bind 294, Nr. 34. s. 12567-12578.

Bibtex

@article{3798c65ae87f4f2fa8563a2d6f9e206c,
title = "Discovery of O-glycans on atrial natriuretic peptide (ANP) that affect both its proteolytic degradation and potency at its cognate receptor",
abstract = "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.",
author = "Hansen, {Lasse H} and Madsen, {Thomas Daugbjerg} and Goth, {Christoffer K} and Henrik Clausen and Yang Chen and Nina Dzhoyashvili and Iyer, {Seethalakshmi R} and Sangaralingham, {S Jeson} and Burnett, {John C} and Rehfeld, {Jens F} and Vakhrushev, {Sergey Y} and Schjoldager, {Katrine T} and Goetze, {Jens P}",
note = "{\circledC} 2019 Hansen et al.",
year = "2019",
month = "8",
day = "23",
doi = "10.1074/jbc.RA119.008102",
language = "English",
volume = "294",
pages = "12567--12578",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc",
number = "34",

}

RIS

TY - JOUR

T1 - Discovery of O-glycans on atrial natriuretic peptide (ANP) that affect both its proteolytic degradation and potency at its cognate receptor

AU - Hansen, Lasse H

AU - Madsen, Thomas Daugbjerg

AU - Goth, Christoffer K

AU - Clausen, Henrik

AU - Chen, Yang

AU - Dzhoyashvili, Nina

AU - Iyer, Seethalakshmi R

AU - Sangaralingham, S Jeson

AU - Burnett, John C

AU - Rehfeld, Jens F

AU - Vakhrushev, Sergey Y

AU - Schjoldager, Katrine T

AU - Goetze, Jens P

N1 - © 2019 Hansen et al.

PY - 2019/8/23

Y1 - 2019/8/23

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.RA119.008102

DO - 10.1074/jbc.RA119.008102

M3 - Journal article

VL - 294

SP - 12567

EP - 12578

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 34

ER -

ID: 58227587