Effect of Sialylated O-glycans in Pro-brain Natriuretic Peptide Stability

Overview

Journal Clin Chem

Publisher Oxford University Press

Specialty Biochemistry

Date 2010 Mar 30

PMID 20348402

Citations 18

Authors

Jingjing Jiang

Nicole Pristera

Wei Wang

Xiumei Zhang

Qingyu Wu

Affiliations

Soon will be listed here.

Abstract

Background: Atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP) are important in regulating a variety of cardiovascular and cellular functions. In cells, these peptides are made as proforms that are converted to mature forms. BNP and its related peptides are biomarkers for the diagnosis of heart failure. In this study, we examined glycosylation in pro-ANP, pro-BNP, and pro-CNP, which may alter their biochemical and metabolic properties.

Methods: Human pro-ANP, pro-BNP, and pro-CNP were expressed in HEK 293 cells and murine HL-1 cardiomyocytes and analyzed by immunoprecipitation and Western blotting. We used deglycosylation enzymes to determine the carbohydrate content on these peptides and examined the effects of inhibiting O-glycosylation on cellular expression and stability of the peptides.

Results: In HEK 293 and HL-1 cells, pro-BNP, but not pro-ANP and pro-CNP, from the culture medium had a greater molecular mass than that from cell lysate. Digestion with PNGase F, O-glycosidase, and sialidase A indicated that pro-BNP contained O-glycans but not N-glycans. The O-glycans on pro-BNP had sialic acids at their termini, protecting it from O-glycosidase digestion. In contrast, pro-ANP and pro-CNP contained no detectable amounts of N- or O-glycans. Inhibition of O-glycosylation on pro-BNP did not prevent its expression in the cells. However, partially O-glycosylated pro-BNP was much less stable than fully O- glycosylated pro-BNP.

Conclusions: O-glycosylation is not necessary for pro-BNP expression but important for its stability.

Citing Articles

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An Overview of Glycosylation and its Impact on Cardiovascular Health and Disease.

Loaeza-Reyes K, Zenteno E, Moreno-Rodriguez A, Torres-Rosas R, Argueta-Figueroa L, Salinas-Marin R Front Mol Biosci. 2021; 8:751637.

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Glycosylated Chromogranin A: Potential Role in the Pathogenesis of Heart Failure.

Ottesen A, Christensen G, Omland T, Rosjo H Curr Heart Fail Rep. 2017; 14(6):478-488.

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