NR APAP
AU Xanthopoulos,K.; Paspaltsis,I.; Apostolidou,V.; Grigoriadis,N.; Sklaviadis,T.K.; Tsirka,S.E.
TI The Activity of tissue Plasminogen Activator (tPA) in Tissues Infected with Transmissible Spongiform Encephalopathies
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-108
PT Konferenz-Poster
AB
Plasminogen is a broad range serine protease precursor, which is converted to the active protease plasmin following proteolysis by either urokinase type plasminogen activator (uPA) or tissue type plasminogen activator (tPA). While uPA seems not to be involved with prion protein, there is mounting evidence for an interaction between tPA mediated plasmin generation and PrP. Binding of plasminogen to PrPsc has been shown, and more recent studies indicate that the prion protein interacts with proteins containing kringle domains. Plasminogen is predicted to have five of them whereas tPA has two. Moreover, stimulation of tPA-induced plasmin generation in the presence of apo-PrP (PrP without Cu2+) has been reported. The NH2-terminal recombinant PrP fragment 23-110, which represents a plasmin cleavage product, has been implicated in the stimulation of the plasmin generation. All the aforementioned data were gathered from experiments using recombinant prions of different species.
In the present work, using a chromogenic plasminogen assay, we demonstrate elevated plasminogen activation in PrPsc-infected brain homogenates from diverse species relative to appropriate control homogenates. These findings are consistent with our RT-PCR findings, which reflect the comparative levels of tPA expression in control and TSE-infected brain. As mentioned above, plasmin has been shown recently to cleave recombinant PrP. Our preliminary results indicate the ability of t-PA generated plasmin to cleave PrPsc purified from of brain extract.
AD K. Xanthopoulos, I. Paspaltsis, V. Apostolidou, T. Sklaviadis, Laboratory of Pharmacology, School of Pharmaceutical Sciences, Aristotle University of Thessaloniki, Greece; N. Grigoriadis, B' Dept. of Neurology and Lab of experimental Neurology, AHEPA University Hospital, Greece; Stella E. Tsirka, Department of nPharamcological Sciences, University Medical Centre at Stony Brook, USA
SP englisch
PO Deutschland