Hierarchical role of fetuin-A and acidic serum proteins in the formation and stabilization of calcium phosphate particles

187Citations
Citations of this article
123Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The serum protein fetuin-A is a potent systemic inhibitor of soft tissue calcification. Fetuin-A is highly effective in the formation and stabilization of protein-mineral colloids, referred to as calciprotein particles (CPPs). These particles ripen in vitro in a two-step process, indicated by a morphological conversion from spheres to larger prolate ellipsoids. Using a combined light scattering and electron microscopic imaging approach we determined that the second-stage particles resulted from a highly anisotropic outgrowth of the first-stage particles. Electron microscopy of ascites fluid from a patient with calcifying peritonitis revealed particles reminiscent of secondary CPPs. Thus, CPPs form in the body and undergo the two-step ripening at least in pathological conditions. Unlike in vitro generated CPPs, ascites-derived CPPs contained little fetuin-A but large amounts of albumin. This prompted us to study the role of fetuin-A combined with other serum proteins in CPP formation. Fetuin-A was indispensable for primary CPP formation. Albumin and acidic proteins in general greatly enhanced the fetuin-A triggered formation of secondary CPPs and, thus, substituted substantial amounts of fetuin-A without loss of inhibition of calcium phosphate precipitation. Thus, direct mineral deposition from solute in the body is unlikely even at low fetuin-A serum levels as long as sufficient bulk acidic protein is available. Collectively fetuin-A and other acidic bulk plasma proteins may be considered as mineral chaperones mediating the stabilization, safe transport, and clearance in the body of calcium and phosphate as colloidal complexes, thus, preventing ectopic calcification. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

Figures

References Powered by Scopus

Analysis of macromolecular polydispersity in intensity correlation spectroscopy: The method of cumulants

2840Citations
N/AReaders
Get full text

The serum protein α<inf>2</inf>-Heremans-Schmid glycoprotein/ fetuin-A is a systemically acting inhibitor of ectopic calcification

848Citations
N/AReaders
Get full text

Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: A cross-sectional study

848Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Regulatory mechanisms in vascular calcification

464Citations
N/AReaders
Get full text

Fetuin-A regulation of calcified matrix metabolism

315Citations
N/AReaders
Get full text

Nanoparticle-based test measures overall propensity for calcification in serum

268Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Heiss, A., Eckert, T., Aretz, A., Richtering, W., Van Dorp, W., Schäfer, C., & Jahnen-Dechent, W. (2008). Hierarchical role of fetuin-A and acidic serum proteins in the formation and stabilization of calcium phosphate particles. Journal of Biological Chemistry, 283(21), 14815–14825. https://doi.org/10.1074/jbc.M709938200

Readers over time

‘09‘10‘11‘12‘13‘14‘15‘16‘17‘18‘19‘20‘21‘22‘23‘24‘2505101520

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 42

55%

Researcher 26

34%

Professor / Associate Prof. 8

11%

Readers' Discipline

Tooltip

Medicine and Dentistry 19

33%

Engineering 15

26%

Agricultural and Biological Sciences 14

24%

Chemistry 10

17%

Article Metrics

Tooltip
Mentions
References: 1

Save time finding and organizing research with Mendeley

Sign up for free
0