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
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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