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Review
. 2013:61:1-31.
doi: 10.1016/b978-0-12-407680-8.00001-4.

BNP molecular forms and processing by the cardiac serine protease corin

Tomoko Ichiki  1 , Brenda K Huntley, John C Burnett Jr
Affiliations
Review

BNP molecular forms and processing by the cardiac serine protease corin

Tomoko Ichiki et al. Adv Clin Chem. 2013.

Abstract

The cardiac hormone, B-type natriuretic peptide (BNP), is one of human natriuretic peptides which possesses cardiorenal protective actions and is used as a therapeutic and a biomarker for heart failure (HF). Its prohormone, proBNP1_108, is processed by the proNPs convertases, corin or furin, to inactive NT-proBNP1_76 and active BNP1-32. Paradoxically, circulating NT-proBNP and BNP are elevated in HF leading to the use of BNP as a sensitive and predictive marker of HF. This paradox may be explained by the "nonspecific" nature of conventional assays and/or a relative deficiency state of "active BNP" as characterized by an increase in inactive proBNP_108 and a decrease in active BNP1-32. Therefore, understanding the regulation of proBNP1_108 processing and the role of the convertase corin may be important in understanding the physiology of HF. Corin is expressed in heart and kidney and may play an important role in regulating blood pressure and remodeling of the heart. The processing of proBNP1_108 by corin may be controlled by O-linked glycosylation of proBNP1-108. A potential impairment of proBNP1lo8 processing in HF may be linked to dysregulation of the convertase corin, which may offer therapeutic opportunities to control proBNPlo0s processing and its activation in HF.

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Figures

Figure 1
Figure 1. PreproBNP1-134 amino acid sequence with sites of processing and degradation
Figure 2
Figure 2. BNP1-32 degradation
BNP1-32 is degraded by DPPIV, NEP or IDE. After IDE degradation, BNP may be a dual activator of GC-A/-B [15, 18, 40].
Figure 3
Figure 3. BNP bioactivity via GC-A and cGMP activation and clearance through NPR-C and degradation pathways
BNP stimulates cGMP activity through binding of GC-A. NPs also bind to the non-GC linked NP clearance receptor (NPR-C). The NPs are degraded by peptidases such as neutral endopeptidase 24.11 (NEP), dipeptidyl peptidase IV (DPP4), and insulin depredating enzyme (IDE).
Figure 4
Figure 4. A schematic structure of human corin gene, the domain structure of corin protein, and corin single nucleotide polymorphisms (SNPs)
[9, 52, 58]
Figure 5
Figure 5. ProBNP processing in normal human circulation
[12] A: The schema of His-tag proBNP1-108 processing. Native sequences are shown as black-closed circle, and tagged Histidines are shown as red-closed circle. B: Representative WB for His-tag protein in healthy volunteers. Number and M or F; Age and Male or Female, +; with His-tag proBNP1-108, −; without His-tag proBNP1-108, MW; Molecular weight. C: The relationship between plasma corin levels and processed BNP.
Figure 6
Figure 6. ProBNP1-108 O-linked glycosylation sites
[74]
See this image and copyright information in PMC

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