NR AOGM
AU Kovalchuk,O.; Tzaban,S.; Tal,Y.; Horonchik,L.; Esko,J.D.; Vlodavsky,I.; Taraboulos,A.
TI Cellular heparan sulfate participates in the metabolism of prions
QU The Journal of Biological Chemistry 2003 Oct 10; 278(41): 40041-40049
PT journal article
AB During prion diseases the host protein PrPc is refolded into an abnormal prionconformer PrPsc. Histological and pharmacological data have suggested that glycosaminoglycans (GAGs) may be involved in the development of prion diseases. Here we present the first direct evidence that cellular GAGs play a role in the biogenesis of PrPsc in prion-infected ScN2a cells. When ScN2a cells were incubated with estradiol-D-xyloside to inhibit the glycosylation of proteoglycans, PrPsc was vastly reduced. Treating ScN2a-M cells with heparinase III, but not with heparinase I or chondroitinase ABC, caused a profound reduction of PrPsc. In contrast, neither the amount of PrPc nor its subcellular distribution were affected, as assayed by immunofluorescence microscopy and flotation procedures. In vitro treatment of ScN2a membranes with heparinase III at either neutral or acidic pH did not reduce the level of protease-resistant PrPsc. The inhibitor of sulfation, sodium chlorate, vastly reduces PrPsc in ScN2a cells (J Cell Physiol 157:319-325). Both soluble heparan sulfate and chondroitin sulfate partially restored the level of PrPsc in chlorate-treated cells. We conclude that heparinase III-sensitive, presumably undersulfated, cellular heparan sulfate play a significant role in the biogenesis of PrPsc in ScN2a cells.
AD Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem 91120.
SP englisch