Characterization of plasma factors that alter the permeability to albumin within isolated glomeruli.

Abstract

Focal segmental glomerulosclerosis (FSGS) is responsible for intractable proteinuria and has become the leading cause of renal insufficiency in children. Protenuria in FSGS is probably due to the effect of one or more permeability plasma factors which increase the glomerular permeability to proteins. We fractioned serum from children with FSGS using two mixed chromatographic-electrophoretic approaches and have purified ten proteins among several hundreds which maintained the original permeability activity after renaturation, utilizing an isolated rat glomeruli assay. Six proteins were successfully characterized by mass spectometry as fibulin, apolipoprotein J, vitronectin, albumin isoforms, gamma chain fibrinogen and mannan-binding lectin-associated serine protease. Both procedures utilized for purification were based on affinity chromatography with Protein A-Sepharose and ended with two-dimensional electrophoresis, whereas the intermediate steps were different. Cross inhibition with zinc and aprotinin of purified factors and whole FSGS serum indicate strong homology. These are the first data demonstrating permeability activity for serum proteins, an observation with important implications in pathogenesis of proteinuria. Determination of the serum levels of each protein and a careful differentiation of FSGS from normal serum could provide the basis for clarifying the mechanism of proteinuria.

• Authors: Luca Musante, Giovanni Candiano, Maurizio Bruschi, Cristina Zennaro, Michele Carraro, Mary Artero, Maria Gabriella Giuffrida, Amedeo Conti, Annalisa Santucci, Gian Marco Ghiggeri
• Journal: Proteomics (Proteomics) Vol. 2 Issue 2 Pg. 197-205 (Feb 2002) ISSN: 1615-9853 [Print] Germany
• PMID: 11840565 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Albumins
• Blood Proteins
• CLU protein, human
• Calcium-Binding Proteins
• Clusterin
• Glycoproteins
• Molecular Chaperones
• Proteome
• Vitronectin
• fibulin
• Fibrinogen
• MASP2 protein, human
• Mannose-Binding Protein-Associated Serine Proteases
• Serine Endopeptidases

Topics

• Adolescent
• Adult
• Albumins (metabolism)
• Amino Acid Sequence
• Animals
• Biological Assay
• Blood Proteins (genetics, isolation & purification, pharmacology)
• Calcium-Binding Proteins (blood)
• Child
• Clusterin
• Fibrinogen (isolation & purification)
• Glomerulosclerosis, Focal Segmental (blood, complications, metabolism)
• Glycoproteins (blood)
• Humans
• In Vitro Techniques
• Kidney Glomerulus (drug effects, metabolism)
• Male
• Mannose-Binding Protein-Associated Serine Proteases
• Molecular Chaperones (blood)
• Molecular Sequence Data
• Permeability
• Proteinuria (blood, etiology, metabolism)
• Proteome (genetics, isolation & purification)
• Rats
• Rats, Sprague-Dawley
• Serine Endopeptidases (blood)
• Vitronectin (blood)