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Received on July 13, 2005
Accepted on October 10, 2005
Proteomics and Protein Markers |
1 Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
2 Diagnostic Radiology Unit, Cliniques Universitaires St-Luc, Université Catholique de Louvain, Brussels, Belgium
3 Cardiovascular Center, Onze Lieve Vrouwziekenhuis, Aalst, Belgium
* To whom correspondence should be addressed. E-mail: ingrid.demeester{at}ua.ac.be.
Background: Analysis of plasma B-type natriuretic peptide (BNP) has suggested the in vivo formation of a truncated form, BNP (3-32), also called des-SerPro-BNP. The objectives of this study were to investigate (a) whether BNP and other natriuretic peptides are truncated by dipeptidyl-peptidase IV (DPP IV/CD26; EC 3.4.14.5) and (b) whether this truncation affects the susceptibility to cleavage by neutral endopeptidase (NEP; EC 3.4.24.11).
Methods: Human BNP (1-32), A-type natriuretic peptide 1-28 (ANP 1-28), and related peptides were incubated with purified DPP IV and with human plasma. In addition, BNP (1-32), BNP (3-32), and ANP (1-28) were subjected to hydrolysis by NEP. Cleavage products were analyzed by mass spectrometry.
Results: BNP (1-32) is cleaved by purified DPP IV with a specificity constant of 0.37 x 106 L · mol-1 · s-1. The DPP IV activity in EDTA-plasma was able to truncate BNP (1-32) ex vivo. Addition of Vildagliptin, a specific DPP IV inhibitor, prevented this truncation in a concentration-dependent manner. Under in vitro circumstances in which ANP was hydrolyzed extensively, BNP (1-32) and BNP (3-32) were very resistant to NEP-mediated cleavage.
Conclusions: DPP IV cleaves BNP (1-32) with an efficiency higher than or comparable to several known in vivo substrates of the enzyme. Even after loss of the amino-terminal dipeptide, BNP remains highly resistant to cleavage by NEP.
The following articles in journals at HighWire Press have cited this article:
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 F. S. Apple, A. H.B. Wu, A. S. Jaffe, M. Panteghini, R. H. Christenson, NACB COMMITTEE MEMBERS, R. H. Christenson, F. S. Apple, C. P. Cannon, G. Francis, et al. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical Issues for Biomarkers of Heart Failure Circulation, July 31, 2007; 116(5): e95 - e98. [Full Text] [PDF]
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G. Boerrigter, L. C. Costello-Boerrigter, G. J. Harty, H. Lapp, and J. C. Burnett Jr. Des-serine-proline brain natriuretic peptide 3-32 in cardiorenal regulation Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R897 - R901. [Abstract] [Full Text] [PDF]
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