The cellular prion protein counteracts cardiac oxidative stress

• Published in: Cardiovascular research 2014-10, Vol.104 (1), p.93-102
• Main 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
• Format: Article
• Language: English
• Subjects: Animals; Catalase - metabolism; Cell Death; Disease Models, Animal; Male; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Muscle Proteins - metabolism; Myocardial Infarction - genetics; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - genetics; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Oxidative Stress; PrPC Proteins - deficiency; PrPC Proteins - genetics; PrPC Proteins - metabolism; Rabbits; Reactive Oxygen Species - metabolism; Shc Signaling Adaptor Proteins - metabolism; Src Homology 2 Domain-Containing, Transforming Protein 1; Time Factors
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvu194

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. 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. Our data demonstrate that PrP(C) contributes to the cardiac mechanisms antagonizing oxidative insults.