NR AXMS
AU Gahali-Sass,I.; Rouvinski,A.; Metzer,E.; Tal,Y.; Makedonski,K.; Nissan,I.; Taraboulos,A.
TI Cholesterol Analogs Modulate Lipids and Hamper Prions in Cultured Cells and Retard Scrapie in Mice
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.45
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
In prion-infected cells, the formation of the scrapie prion protein PrPsc from its normal precursor PrPc seems to be controlled by lipid rafts, but the mechanisms remain obscure. Lipid rafts are lateral, partially ordered assemblies of cholesterol and of sphingolipids within cellular membranes. Because natural cholesterol analogs vary in their propensity to form ordered lipid domains in vitro, they may provide a way to modulate rafts in vivo. We report that several sterols modified rafts and their lipids and reduced prions in chronically infected ScN2a and ScGT1 cells. Cholesterol sulfate, a poor domain former, and dehydroepiandrosterone (DHEA) both decreased PrPsc but had diametrically contrasting effects on rafts. CholSO4 reduced free cholesterol,
ganglioside GM1 and the migration of raft markers in flotation gradients, whereas these parameters were increased by DHEA. CholSO4 delayed the internalization of cell
surface PrPc, which is thought to precede PrPsc formation. Interestingly, CholSO4 appeared to insert into bilayers and to substitute for cholesterol, a possible explanation for its low cytotoxicity in the face of these vast lipid changes. Disequilibrium of raft lipids may thus alter prion propagation, perhaps by altering subcellular trafficking pathways. In mice, DHEA prolonged the incubation time of RML experimental scrapie by two weeks. These results point to a novel class of potential anti-prion agents and introduce exogenous sterols as an attractive tool to study cellular aspects of lipid rafts (supported by EC grant QLK2-CT-2002-81628 and by the Israel Prion Center).
AD I. Gahali-Sass, A. Rouvinski, E. Metzer, Y. Tal, K. Makedonski, I. Nissan, A. Taraboulos, Hebrew University - Hadassah Medical School and the Israel Prion Center, Department of Molecular Biology, Israel
SP englisch
PO Schottland
EA pdf-Datei und Poster (Posterfoto leider völlig unscharf und damit mit Ausnahme des Titels unlesbar)