NR AXWY
AU Sorgato,M.C.; Menabo,R.; Massimino,M.L.; Bertoli,A.; Di Lisa,F.; Sorgato,M.C.
TI Intact Hearts: A New Tool for Elucidating the Physiology of the Prion Protein
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.52
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
The elusive function of PrPc hampers the understanding of the molecular mechanism at the basis of prion diseases, and the development of suitable therapeutic protocols. Use of cell model systems, and genetically modified animals, have nevertheless suggested a number of potential roles for the protein, ranging from cell survival to differentiation. Because we now know that muscle is involved in PrPc pathophysiology, we have considered intact heart paradigms for the in situ study of the cell-protecting function of PrPc. Isolated muscle organs retain the cell native environment and are also more suitable to experimental designs than whole animals. Accordingly, by taking advantage of mice expressing different PrPc amounts (WT, KO and overexpressors), the protection of PrPc against cell oxidative injuries was investigated in isolated hearts subjected to ischemia/reperfusion protocols that involve oxidative stress. Our prediction was that hearts from adult PrPc-null mice manifest an overt phenotype after transient, or long-lasting, ischemia, resulting in exacerbation of heart oxidative injuries. Conversely, PrPc overexpressing mice should demonstrate a higher resistance over ROS production. Myocardial viability was assessed by lactic dehydrogenase (LDH) release into the coronary effluent, while quantification, by immunoblot assays, of myocardial damage was based on myofibrillar protein oxidation.
We found that in PrPc-KO hearts 30 min-reperfusion after 45 min of no-flow ischemia was associated with a larger LDH release, compared to hearts from WT mice. Conversely, hearts from overexpressors displayed a decreased susceptibility to reperfusion injury. The protection by PrPc over ROS damage was also evident from the myofibrillar oxidation pattern of the hearts isolated from the different animals. This data thus supports both the value of the in situ muscle paradigm and the role of PrPc against oxidative insults.
AD M.C. Sorgato, R. Menabò, M.L. Massimino, A. Bertoli, F. Di Lisa, M.C. Sorgato, University of Padova, Italy
SP englisch
PO Schottland