NR AXRN
AU Löfgren,K.; Wahlström,A.; Lundberg,P.; Langel,U.; Gräslund,A.; Bedecs,K.
TI Mouse PrP(1-28) Peptide Reduces PrPsc Levels in a Scrapie Infected Mouse Hypothalamic Cell Line
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.21
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Cell penetrating peptides (CPPs) are a heterogeneous group of short peptides capable of penetrating cellular membranes and translocate linked macromolecules into a variety of cells. Heparan sulfate proteoglycans (HSPGs) have been proposed to be implicated in the uptake mechanism of certain types of CPPs. Evidence suggests a foremost endocytic, lipid raft-dependent form of uptake although alternative, competitive and/or parallel entry mechanisms may also exist. The N-terminal (1-28) part of the mouse prion protein (mPrP(1-28)) has CPP-like properties and it may interact with HSPGs. In addition, HSPGs are considered to be involved in conversion of the cellular prion protein (PrPc) to the misfolded and pathogenic isoform of the prion protein (PrPsc). This led us to investigate whether presence of CPPs may interfere with prion infection by competitive binding to the cellular HSPGs involved in PrPsc
propagation. Healthy (GT1-1) and scrapie-infected (ScGT1-1) mouse neuronal hypothalamic cell lines were cultured in the presence of different CPPs across a range of concentrations and time spans. Cell extracts were analyzed by Western blot for relative levels of PrPc (GT1-1) or PrPsc (ScGT1-1) compared to untreated control cultures. Treatment with mPrP(1-28) reduced PrPsc levels in ScGT1-1 cells, but did not affect the PrPc levels in GT1-1. This effect is sequence specific since treatments with
other CPPs or PrP peptides tested (transportan-10, penetratin, poly-L-arginine, mPrP(23-50) or bovine PrP(1-30)) resulted in no reduction of PrPsc levels in ScGT1-1 cell cultures. Taken together, these results may provide important clues to the process of PrPsc conversion.
AD K. Lofgren, A. Wahlstrom, A. Graslund, K. Bedecs, The Arrhenius Laboratories for Natural Sciences, Stockholm University, Department of Biochemistry and Biophysics, Sweden; P. Lundberg, U. Langel, The Arrhenius Laboratories for Natural Sciences, Stockholm University, Department of Neurochemistry, Sweden
SP englisch
PO Schottland
EA pdf-Datei und Poster (Titel: Prion protein-derived cell penetrating peptides reduce PrPsc levels in prion-infected neuronal cells)