NR AEHB
AU Gabizon,R.; Meiner,Z.; Halimi,M.; Ben-Sasson,S.A.
TI Heparin-like molecules bind differentially to prion-proteins and change their intracellular metabolic fate
QU Journal of Cellular Physiology 1993 Nov; 157(2): 319-25
PT journal article
AB PrPsc is the only known component of the scrapie prion. The difference between PrPsc and its normal isoform PrPc is probably conformational, since no difference has been found in the amino acid sequence or postranslational modifications between both proteins. Heparan sulfate (HS) has been shown to be a component of amyloid plaques in a number of diseases including the prion diseases. We now present evidence that PrP can specifically bind to heparin-like compounds and that this interaction might have a physiological significance. HS can increase the concentration of PrP in normal neuroblastoma cells, whereas low molecular weight heparin (LMWH) does not. In contrast, LMWH and other heparin-like molecules, excluding HS, can inhibit the synthesis of PrPsc in scrapie infected cells and reverse their phenotype back to normal as judged by measurement of PrPsc by immunoblotting and by infectivity experiments. Whether an interaction between PrP and glycosaminoglycans plays a direct role in the conversion of PrPc into PrPsc remains to be established.
MH Amino Acids/analysis/metabolism; Amyloid/analysis/metabolism; Animal; Chlorates/pharmacology; Comparative Study; Glycosaminoglycans/metabolism; Heparin/analysis/*metabolism; Heparitin Sulfate/analysis/metabolism/physiology; Immunohistochemistry; Isomerism; Mice; Neuroblastoma/chemistry/metabolism/pathology; Phenotype; PrPsc Proteins; Prions/analysis/*metabolism; Protein Conformation; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Time Factors; Tumor Cells, Cultured
AD Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
SP englisch
PO USA