The cellular prion protein counteracts cardiac oxidative stress. (18th August 2014)

• Record Type: Journal Article
• Authors: Zanetti, Filippo; Carpi, Andrea; Menabò, Roberta; Giorgio, Marco; Schulz, Rainer; Valen, Guro; Baysa, Anton; Massimino, Maria Lina; Sorgato, Maria Catia; Bertoli, Alessandro; Di Lisa, Fabio
• Is Part Of: Cardiovascular research. Volume 104:Number 1(2015)
• Page Start: 93
• Page End: 102
• Publication Date: 2014-08-18
• Subjects: Cellular prion protein -- PrP -- Oxidative stress -- Heart -- ROS; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvu194
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: Aims: 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. Methods and 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 H2 O2 . 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.