INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Differential binding to extracellular matrix components of a natural apolipoproteinA I variant associated with cardiac amyloidosis
Autor/es:
GISONNO, ROMINA; URBANO, BRUNO; M. A. TRICERRI; CORTEZ, M. FERNANDA; ROSU, S. A; SANCHEZ DONOSO SUSANA; CALABRESE, GRACIELA C.; RAMELLA, N. A
Lugar:
Buenos Aires
Reunión:
Congreso; Reunión Anul de Sociedades de Biociencia; 2020
Institución organizadora:
SAIC, SAFIS, SAI
Resumen:
Specific interactions of apolipoproteins with components of the extracellular matrix (ECM), as proteoglycans (PGs), are associated with amyloidosis or atherosclerosis. These interactions seem to depend on age, cellular differentiation, and pathological conditions, which might modify glycosaminoglycans (GAGs) composition. We previously showed that apoA-I Arg173Pro (a natural mutant involved in cardiac amyloidosis) but not the wild type protein (Wt) bound heparin at pH 7.4 This indicates that selective interactions of this variant may occur with GAGs. To study the specific role of the matrix?s charge on the interaction of apoA-I with GAGs, we synthesized polymers having different ratios of sulfated (sodium 4-styrene sulfonate, (SSNa) or hydroxilated monomers (2-hydroxyethyl methacrylate, (HEMA)) and studied the binding of fluorescently labelled apoA-I Wt or Arg173Pro. We show that both proteins are highly retained as long as the negative charge increases (50% with p ≤0.05 as negative charge of the SSNa increased from 0.25 to 0.75 M). In addition, Arg173Pro remained in the matrix 10 % more than Wt (p < 0.01), indicating that the retention of specific proteins in the ECM could be part of the pathogenicity. To analyze the differential interaction with GAGs, Wt or Arg173Pro were incubated in the presence of Dermatan Sulfate (DS) or sodium heparin (HEP). The samples (n=4), were centrifuged, and pellets and supernatants analyzed by polyacrylamide gel electrophoresis. GAGs were visualized by staining with toluidine blue and the proteins with Silver stain. We observed that Arg173Pro had more interaction with DS and HEP than the Wt variant, which is interesting, since both GAGs are associated with amyloid deposits and heart disease, respectively. We conclude that the interactions of apoA-I variants with GAGs offer a challenging field to understand, not only the pathology but also possible therapeutic strategies to treat this disease.