Abstract
Natriuretic peptides (NPs) are hormones involved in maintaining heart health that undergo proteolytic cleavage to become activated. Previous work has shown that O-GalNAc glycans affect their processing and activation. Here, Goetze, Schjoldager, and colleagues now provide comprehensive characterization of O-glycosylation of NPs, revealing that all members of the NP family can be modified by O-GalNAc glycans. Intriguingly, the study discovers glycans in the receptor-binding region of the A-type natriuretic peptide (ANP), demonstrating that they affect both stability and activity of ANP. These results may inform future therapeutic approaches for heart failure using peptide glycoforms.
Highlights
NPs2 are critical hormones that protect the heart from damage
NPs are synthesized as prohormones that undergo processing by furin or corin to generate mature, active forms with an obligate 17-residue disulfidebonded C-terminal ring [5]
They act as hormones by binding and activating their receptors, the transmembrane guanylyl cyclases A and B, elevating intracellular cGMP concentration and regulating the cardiovascular, skeletal, nervous, and renal systems
Summary
NPs2 are critical hormones that protect the heart from damage. They constitute three types of structurally related signaling. ANP and BNP are secreted by the heart in response to myocardium stretching and rapidly removed from circulation by receptor-mediated clearance or through the action of specific proteases, such as neprilysin and insulin-degrading enzyme [5]. Previous studies demonstrated that the BNP precursor proBNP is modified with O-GalNAc glycans near the furin-processing site that can block furin cleavage, indicating that O-glycosylation can result in decreased overall BNP activity [7,8,9].
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