NR ACJS
AU Caughey,B.W.; Brown,K.; Raymond,G.J.; Katzenstein,G.E.; Thresher,W.
TI Binding of the protease-sensitive form of PrP (prion protein) to sulfated glycosaminoglycan and congo red [corrected]
QU Journal of Virology 1994 Apr; 68(4): 2135-41
ER J Virol 1994 Jun;68(6):4107
PT journal article
AB Congo red and certain sulfated glycans are potent inhibitors of protease-resistant PrP accumulation in scrapie-infected cells. One hypothesis is that these inhibitors act by blocking the association between protease-resistant PrP and sulfated glycosaminoglycans or proteoglycans (e.g., heparan sulfate proteoglycan) that is observed in amyloid plaques of scrapie-infected brain tissue. Accordingly, we have investigated whether the apparent precursor of protease-resistant PrP, protease-sensitive PrP, binds to Congo red and heparin, a highly sulfated glycosaminoglycan with an inhibitory potency like that of heparan sulfate. Protease-sensitive PrP released from the surface of mouse neuroblastoma cells bound to heparin-agarose and Congo red-glass beads. Sucrose density gradient fractionation provided evidence that at least some of the PrP capable of binding heparin-agarose was monomeric. Free Congo red blocked PrP binding to heparin and vice versa, suggesting that these ligands share a common binding site. The relative efficacies of pentosan polysulfate, Congo red, heparin, and chondroitin sulfate in blocking PrP binding to heparin-agarose corresponded with their previously demonstrated potencies in inhibiting protease-resistant PrP accumulation. These results are consistent with the idea that sulfated glycans and Congo red inhibit protease-resistant PrP accumulation by interfering with the interaction of PrP with an endogenous glycosaminoglycan or proteoglycan.
IN Kongorot und bestimmte sulphatierte Glycosaminoglycane wie Pentosanpolysulfat, Chondroitinsulfat, Heparin und Heparansulphat sind potente Inhibitoren der Akkumulation proteaseresistenter Prionproteine in scrapieinfizierten Zellen. Sie scheinen die noch proteaseempfindlichen normalen Prionproteine an der selben Stelle zu binden und eine Bindung an die endogenen Glycosaminoglycanen und Proteoglycanen.
MH Animal; Congo Red/*metabolism; Endopeptidases/metabolism; Glass; Heparan Sulfate Proteoglycan; Heparitin Sulfate/*metabolism; Mice; Nerve Tissue/metabolism; Nerve Tissue Proteins/immunology/isolation & purification/*metabolism; Pentosan Sulfuric Polyester/pharmacology; PrPsc Proteins; Precipitin Tests; Prions/immunology/isolation & purification/*metabolism; Protein Binding/drug effects; Protein Precursors/immunology/isolation & purification/*metabolism; Proteoglycans/*metabolism; Tumor Cells, Cultured
AD Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, Hamilton, Montana 59840.
SP englisch
PO USA