NR ATGY
AU Malaise,M.E.L.; Brabeck,C.; Legler,D.; Bürkle,A.
TI Roles of Cellular Prion Protein in Oxydative Stress and Mitochondrial Function
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-04
PT Konferenz-Poster
AB The cellular isoform of prion protein (PrPc) is a GPI-anchored glycoprotein located on the outer surface of the plasma membrane that plays an essential role in the pathogenesis of transmissible spongiform encephalopathies. Despite being the subject of many recent studies, the physiological function of PrPc remains largely unresolved. Several candidate functions have been discussed, including binding and internalisation of copper or other metals, superoxide dismutase-like activity, regulation of cellular antioxidant activities and signal transduction. We have focussed on the TM1 region of PrPc (codons 110-135), due to its high conservation and the neurotoxicity of peptides derived from this region. To elucidate the physiological role of the PrPc TM1 domain in the context of the full-length PrPc molecule, we have constructed a set of deletion mutants centred on codons 114-121 of PrPc. Our aim is to elucidate a possible role of PrPc in anti-oxidative defence in cultured cells. For this purpose we have studied for the effect of overexpression of wt- or delta114-121-PrP in N2A mouse neuroblastoma cells on intracellular level of reactive oxygen species (ROS). Endogenous ROS production was significantly lower in cells transfected with either wt or delta114-121 expression plasmids. Furthermore the mitochondrial membrane potential was significantly lowered in wt-PrP or delta114-121-PrP transfected cells. We conclude that PrPc controls endogenous ROS levels and mitochondrial function. To investigate the impact of endogenous PrPc in the above cell transfection experiments, we are currently studying primary brain cells derived from transgenic mice expressing delta114-121-PrP in different genetic backgrounds (Prnp+/+, Prnp+/-, Prnp-/-).
AD Muriel E.L. Malaise, Christine Brabeck, Alexander Bürkle, Molecular Toxicoly Group, University of Konstanz, Germany; Daniel Legler, Immunology Group, University of Konstanz, Germany
SP englisch
PO Deutschland