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Modulation of calcium oxalate dihydrate growth by phosphorylated osteopontin peptides.
Chien, Yung-Ching; Mansouri, Ahmad; Jiang, Wenge; Khan, Saeed R; Gray, Jeffrey J; McKee, Marc D.
Afiliação
  • Chien YC; Faculty of Dentistry, McGill University, Montreal, QC, Canada.
  • Mansouri A; Faculty of Dentistry, McGill University, Montreal, QC, Canada.
  • Jiang W; Faculty of Dentistry, McGill University, Montreal, QC, Canada.
  • Khan SR; Department of Urology, College of Medicine, University of Florida, FL, USA.
  • Gray JJ; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • McKee MD; Faculty of Dentistry, McGill University, Montreal, QC, Canada; Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Montreal, QC, Canada. Electronic address: marc.mckee@mcgill.ca.
J Struct Biol ; 204(2): 131-144, 2018 11.
Article em En | MEDLINE | ID: mdl-30016645
ABSTRACT
Osteopontin (OPN) is a significant component of kidney stone matrix and a key modulator of stone formation. Here, we investigated the effects of different phosphorylated states of a synthesized peptide of OPN (the ASARM peptide; acidic, serine- and aspartate-rich motif) on calcium oxalate dihydrate (COD) crystals, a major mineral phase of kidney stones. In vitro, phosphorylated OPN-ASARM peptides strongly inhibited COD crystal growth in solution as compared to the nonphosphorylated state, with increasing inhibitory potency correlating with the degree of peptide phosphorylation. Scanning electron microscopy revealed that the inhibition from the phosphopeptides resulted in distinctive, rosette-like crystal aggregates called spherulites. The OPN-ASARM peptides preferentially bound and specifically inhibited the {1 1 0} crystallographic faces of COD, as identified by combining atomic force microscopy and computational simulation approaches. These {1 1 0} surfaces of COD have high lattice calcium occupancy (exposure), providing preferential binding sites for the highly acidic peptides; binding and inhibition by OPN-ASARM peptides at the {1 1 0} faces led to crystal aggregation and intergrowth. The crystal spherulite formations obtained in vitro when using the most phosphorylated form of OPN-ASARM peptide at a high concentration, resembled crystal morphologies observed in vivo in a rat model of urolithiasis, in which crystal deposits in the kidney contain abundant OPN as revealed by immunogold labeling. A mechanistic model for spherulite formation is proposed based on the symmetry and crystallographic structure of COD, where the phosphate groups of OPN-ASARM bind to calcium atoms at [1 1 1] step risers on the COD {1 1 0} surface, inducing the periodic emergence of new COD crystals to form spherulites.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxalato de Cálcio / Osteopontina Limite: Humans Idioma: En Revista: J Struct Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxalato de Cálcio / Osteopontina Limite: Humans Idioma: En Revista: J Struct Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Canadá
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