NR AOWE
AU Maissen,M.; Aguzzi,A.
TI Inhibition of Protease-Resistant Prion Protein Accumulation in Scrapie-Infected Neuroblastoma Cells by Serum Deprivation
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-106
PT Konferenz-Poster
AB Inhibition of the accumulation of protease-resistant prion protein (PrPres) is a prime strategy in the development of potential transmissible spongiform encephalopathy (TSE) therapeutics. Numerous structurally unrelated compounds, including congo red, chlorpromazine, quinacrine, and curcumin, inhibit PrPres formation in prion-infected murine neuroblastoma (N2aSc) cells. However, the mechanism of inhibition of PrPres accumulation by any of these substances is not understood. We found that culture of N2aSc cells in serum-free medium or medium containing only 0.1 % FCS for three days leads to almost complete disappearance of PrPres, as assessed by cell blot and Western blot assays. Cell viability was not impaired. To investigate whether the expression level of the cellular prion protein (PrPc) on the surface of N2aSc was reduced by serum deprivation, we incubated the cells with phospholipase C and measured by Western blotting the amount of PrPc released by the enzyme from the surface of the cells. The expression level of the cellular prion protein (PrPc) in N2aSc cells grown for three days in serum-free medium was similar to that of N2aSc cells cultured in medium containing 10% FCS. Therefore, abrogation of PrPsc did not result from generic impairment of cellular metabolism or from cell death. We conclude that serum starvation appears to activate a cellular antiprion response, whose molecular nature we are currently seeking to define.
AD M. Maissen, A. Aguzzi, Institut of Neuropathology, University Hospital, Zürich, CH
SP englisch
PO Deutschland