NR ALMI
AU Tatzelt,J.; Zuo,J.R.; Voellmy,R.; Scott,M.R.D.; Hartl,U.; Prusiner,S.B.; Welch,W.J.
TI Scrapie prions selectively modify the stress response in neuroblastoma cells
QU Proceedings of the National Academy of Sciences of the United States of America 1995 Mar 28; 92(7): 2944-8
PT journal article
AB The fundamental event underlying scrapie infection seems to be a conformational change in the prion protein. To investigate proteins that might feature in the conversion of the cellular prion protein (PrPc) into the scrapie isoform (PrPsc), we examined mouse neuroblastoma N2a cells for the expression and cellular distribution of heat shock proteins (Hsps), some of which function as molecular chaperones. In scrapie-infected N2a (ScN2a) cells, Hsp72 and Hsp28 were not induced by heat shock, sodium arsenite, or an amino acid analog, in contrast to uninfected control N2a cells, while other inducible Hsps were increased by these treatments. Following heat shock of the N2a cells, constitutively expressed Hsp73 was translocated from the cytoplasm into the nucleus and nucleolus. In contrast, the distribution of Hsp73 in ScN2a cells was not altered by heat shock; the discrete cytoplasmic structures containing Hsp73 were largely resistant to detergent extraction. These alterations in the expression and subcellular translocation of specific Hsps in ScN2a cells may reflect the cellular response to the accumulation of PrPsc. Whether any of these Hsps feature in the conversion of PrPc into PrPsc or the pathogenesis of prion diseases remains to be established.
IN Scrapie-Infektionen bewirken bei N2a-Maus-Neuroblastomzellen unterschiedliche Veränderungen der Expression und Lokalisation von Hitzeschockproteinen. Die Hitzeschockproteine Hsp72 und Hsp28 werden nicht mehr induzierbar, während andere Hitzeschockproteine induzierbar bleiben. Während das nach einem Hitzeschock konstitutiv exprimierte Hitzeschockprotein Hsp73 normalerweise vom Cytoplasma in den Kern wandert, bleibt es in scrapieinfizierten Zellen unverändert im Cytoplasma.
ZR 46
MH Animal; Cell Line; DNA-Binding Proteins/analysis/*biosynthesis; Heat; Heat-Shock Proteins/antagonists & inhibitors/*biosynthesis; Human; Mice; Neuroblastoma; Prions/biosynthesis/*metabolism; Rats; Scrapie/*virology; Subcellular Fractions/metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transcription Factors/biosynthesis; Tumor Cells, Cultured
AD Department of Neurology, University of California, San Francisco 94143, USA
SP englisch
PO USA