title: The cellular prion protein counteracts cardiac oxidative stress.
abstract: OBJECTIVE
  The cellular prion protein, PrP(C), whose aberrant isoforms are related to prion diseases of humans and animals, has a still obscure physiological function. Having observed an increased expression of PrP(C) in two in vivo paradigms of heart remodelling, we focused on isolated mouse hearts to ascertain the capacity of PrP(C) to antagonize oxidative damage induced by ischaemic and non-ischaemic protocols.
  
  
  RESULTS
  Hearts isolated from mice expressing PrP(C) in variable amounts were subjected to different and complementary oxidative perfusion protocols. Accumulation of reactive oxygen species, oxidation of myofibrillar proteins, and cell death were evaluated. We found that overexpressed PrP(C) reduced oxidative stress and cell death caused by post-ischaemic reperfusion. Conversely, deletion of PrP(C) increased oxidative stress during both ischaemic preconditioning and perfusion (15 min) with H2O2. Supporting its relation with intracellular systems involved in oxidative stress, PrP(C) was found to influence the activity of catalase and, for the first time, the expression of p66(Shc), a protein implicated in oxidative stress-mediated cell death.
  
  
  CONCLUSIONS
  Our data demonstrate that PrP(C) contributes to the cardiac mechanisms antagonizing oxidative insults.
authors.affiliation: Department of Biomedical Science, University of Padova, Padova, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Zanetti
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carpi
authors.affiliation: CNR Institute of Neuroscience, University of Padova, Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Menabò
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Giorgio
authors.affiliation: Institut für Physiologie, Justus-Liebig Universität, Gießen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.affiliation: Department of Physiology, University of Oslo, Oslo, Norway.
authors.forename: Guro
authors.initials: G
authors.lastname: Valen
authors.affiliation: Department of Physiology, University of Oslo, Oslo, Norway.
authors.forename: Anton
authors.initials: A
authors.lastname: Baysa
authors.affiliation: CNR Institute of Neuroscience, University of Padova, Padova, Italy.
authors.forename: Maria Lina
authors.initials: ML
authors.lastname: Massimino
authors.affiliation: Department of Biomedical Science, University of Padova, Padova, Italy CNR Institute of Neuroscience, University of Padova, Padova, Italy.
authors.forename: Maria Catia
authors.initials: MC
authors.lastname: Sorgato
authors.affiliation: Department of Biomedical Science, University of Padova, Padova, Italy alessandro.bertoli@unipd.it dilisa@bio.unipd.it dilisa@civ.bio.unipd.it fabio.dilisa@gmail.com.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertoli
authors.affiliation: Department of Biomedical Science, University of Padova, Padova, Italy alessandro.bertoli@unipd.it dilisa@bio.unipd.it dilisa@civ.bio.unipd.it fabio.dilisa@gmail.com.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Lisa
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D016923:Cell Death; D004195:Disease Models, Animal; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D018621:PrPC Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013997:Time Factors
chemical_list: D009124:Muscle Proteins; D018621:PrPC Proteins; D017382:Reactive Oxygen Species; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D002374:Catalase
keywords: Cellular prion protein; Heart; Oxidative stress; PrP; ROS