title: Hydroxychloroquine Protects against Cardiac Ischaemia/Reperfusion Injury In Vivo via Enhancement of ERK1/2 Phosphorylation.
abstract: An increasing number of investigations including human studies demonstrate that pharmacological ischaemic preconditioning is a viable way to protect the heart from myocardial ischaemia/reperfusion (I/R) injury. This study investigated the role of hydroxychloroquine (HCQ) in the heart during I/R injury. In vitro and in vivo models of myocardial I/R injury were used to assess the effects of HCQ. It was found that HCQ was protective in neonatal rat cardiomyocytes through inhibition of apoptosis, measured by TUNEL and cleaved caspase-3. This protection in vitro was mediated through enhancement of ERK1/2 phosphorylation mediated by HCQ in a dose-dependent fashion. A decrease in infarct size was observed in an in vivo model of myocardial I/R injury in HCQ treated animals and furthermore this protection was blocked in the presence of the ERK1/2 inhibitor U0126. For the first time, we have shown that HCQ promotes a preconditioning like protection in an in vivo simulated rat myocardial I/R injury model. Moreover, it was shown that HCQ is protective via enhanced phosphorylation of the pro-survival kinase ERK1/2.
authors.affiliation: Centre for Rheumatology, Division of Medicine University College London, Rayne Institute, London, United Kingdom.|Arthritis Research UK Centre for Adolescent Rheumatology, University College London, London, United Kingdom.
authors.forename: Lauren
authors.initials: L
authors.lastname: Bourke
authors.affiliation: Biochemistry Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health & Great Ormond Street Hospital, University College London, London, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: McCormick
authors.affiliation: UCL Centre for Advanced Biomedical Imaging, Division of Medicine, London, United Kingdom.
authors.forename: Valerie
authors.initials: V
authors.lastname: Taylor
authors.affiliation: Centre for Rheumatology, Division of Medicine University College London, Rayne Institute, London, United Kingdom.
authors.forename: Charis
authors.initials: C
authors.lastname: Pericleous
authors.affiliation: Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Unité Fonctionnelle de Pharmacocinétique et Pharmacochimie, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Blanchet
authors.affiliation: Université René Descartes; Centre de référence maladies auto-immunes et systémiques rares, Service de Médecine Interne, Pôle médecine, Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Costedoat-Chalumeau
authors.affiliation: UCL Centre for Advanced Biomedical Imaging, Division of Medicine, London, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stuckey
authors.affiliation: UCL Centre for Advanced Biomedical Imaging, Division of Medicine, London, United Kingdom.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lythgoe
authors.affiliation: Medical and Molecular Biology Unit, University College London, London, United Kingdom.
authors.forename: Anastasis
authors.initials: A
authors.lastname: Stephanou
authors.affiliation: Centre for Rheumatology, Division of Medicine University College London, Rayne Institute, London, United Kingdom.|Arthritis Research UK Centre for Adolescent Rheumatology, University College London, London, United Kingdom.
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Ioannou
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002070:Butadienes; D009124:Muscle Proteins; D009570:Nitriles; C113580:U 0126; D006886:Hydroxychloroquine; D048052:Mitogen-Activated Protein Kinase 3; C505410:Casp3 protein, rat; D053148:Caspase 3