Lebetin 2, a Snake Venom-Derived Natriuretic Peptide, Attenuates Acute Myocardial Ischemic Injury through the Modulation of Mitochondrial Permeability Transition Pore at the Time of Reperfusion
Autor: | Elise Belaidi, Naziha Marrakchi, Jessica Morand, Mohamed Elayeb, Diane Godin-Ribuot, Bochra Tourki, Erij Messadi, Philippe Mateo |
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Přispěvatelé: | Pasteur Tunis, Institut, Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Carthage - University of Carthage, Signalisation et physiopathologie cardiaque, Université Paris-Sud - Paris 11 (UP11)-IFR141-Institut National de la Santé et de la Recherche Médicale (INSERM), HP2 : Hypoxie et physiopathologies cardiovasculaires et respiratoires., Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de Grenoble , Centre Hospitalier Universitaire de Grenoble, France-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), This work was supported by the Réseau International des Instituts Pasteur (RIIP), the Institut Pasteur de Tunis, INSERM and the Ministère de l’Enseignement Supérieur et de la Recherche de Tunisie. B. Tourki was supported by a grant-in-aid from the Pasteur Institutes Network., We wish to thank Dr C. Arnaud (Laboratoire HP2, INSERM, Grenoble, France), Pr C. Batandier (Laboratoire de Bioénergetique Fondamentale Appliquée, Grenoble, France) and Pr R. Clapier-Ventura (Laboratoire de Signalisation et Physiopathologie Cardiovasculaire, UMR-S 1180, Paris, France) for technical assistance and help and Dr Z. Benlasfar (Institut Pasteur de Tunis, Tunisia) for providing the viper venom. We are grateful to Pr H. Louzir, head of Pasteur Institute of Tunis, for support. |
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
MESH: Signal Transduction
0301 basic medicine Male Critical Care and Emergency Medicine [SDV]Life Sciences [q-bio] Peptide Hormones Myocardial Infarction lcsh:Medicine MESH: Cardiotonic Agents/pharmacology 030204 cardiovascular system & hematology Pharmacology Toxicology Pathology and Laboratory Medicine Vascular Medicine Biochemistry Mitochondrial Membrane Transport Proteins chemistry.chemical_compound 0302 clinical medicine Ischemia Natriuretic peptide Medicine and Health Sciences Toxins MESH: Animals Post-Translational Modification Phosphorylation Receptor lcsh:Science Energy-Producing Organelles Cardioprotection Multidisciplinary biology Heart MESH: Myocardial Infarction/pathology [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Mitochondria [SDV] Life Sciences [q-bio] Cardiology Signal transduction Anatomy Cellular Structures and Organelles Research Article Signal Transduction medicine.medical_specialty MESH: Myocardial Reperfusion Injury/prevention & control Cardiotonic Agents MESH: Rats medicine.drug_class Toxic Agents Myocardial Reperfusion Injury Viper Venoms Bioenergetics In Vitro Techniques 03 medical and health sciences Mitochondrial membrane transport protein [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Natriuretic Peptide Internal medicine medicine Animals cardiovascular diseases Rats Wistar Cyclic guanosine monophosphate MESH: In Vitro Techniques MESH: Viper Venoms/pharmacology business.industry Venoms Mitochondrial Permeability Transition Pore Myocardium lcsh:R Biology and Life Sciences Proteins MESH: Rats Wistar Cell Biology medicine.disease MESH: Male Hormones Rats 030104 developmental biology MESH: Mitochondrial Membrane Transport Proteins/drug effects Mitochondrial permeability transition pore chemistry Reperfusion biology.protein Cardiovascular Anatomy lcsh:Q business |
Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 9, p e0162632 (2016) PLoS ONE, 2016, 11 (9), pp.e0162632. ⟨10.1371/journal.pone.0162632.s006⟩ PLoS ONE, Public Library of Science, 2016, 11 (9), pp.e0162632. ⟨10.1371/journal.pone.0162632.s006⟩ |
ISSN: | 1932-6203 |
Popis: | International audience; Cardiac ischemia is one of the leading causes of death worldwide. It is now well established that natriuretic peptides can attenuate the development of irreversible ischemic injury during myocardial infarction. Lebetin 2 (L2) is a new discovered peptide isolated from Macrovipera lebetina venom with structural similarity to B-type natriuretic peptide (BNP). Our objectives were to define the acute cardioprotective actions of L2 in isolated Langendorff-perfused rat hearts after regional or global ischemia-reperfusion (IR). We studied infarct size, left ventricular contractile recovery, survival protein kinases and mitochondrial permeability transition pore (mPTP) opening in injured myocardium. L2 dosage was determined by preliminary experiments at its ability to induce cyclic guanosine monophosphate (cGMP) release without changing hemodynamic effects in normoxic hearts. L2 was found to be as effective as BNP in reducing infarct size after the induction of either regional or global IR. Both peptides equally improved contractile recovery after regional IR, but only L2 increased coronary flow and reduced severe contractile dysfunction after global ischemia. Cardioprotection afforded by L2 was abolished after isatin or 5-hydroxydecanote pretreatment suggesting the involvement of natriuretic peptide receptors and mitochondrial KATP (mitoKATP) channels in the L2-induced effects. L2 also increased survival protein expression in the reperfused myocardium as evidenced by phosphorylation of signaling pathways PKCε/ERK/GSK3β and PI3K/Akt/eNOS. IR induced mitochondrial pore opening, but this effect was markedly prevented by L2 treatment. These data show that L2 has strong cardioprotective effect in acute ischemia through stimulation of natriuretic peptide receptors. These beneficial effects are mediated, at least in part, by mitoKATP channel opening and downstream activated survival kinases, thus delaying mPTP opening and improving IR-induced mitochondrial dysfunction. |
Databáze: | OpenAIRE |
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