Academic Journal
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.
| العنوان: | 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. |
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| المؤلفون: | Tourki, Bochra, Matéo, Philippe, Morand, Jessica, Elayeb, Mohamed, Marrakchi, Naziha, Godin-Ribuot, Diane, Belaidi, Elise, Messadi, Erij |
| المساهمون: | Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur), Université de Carthage (Tunisie) (UCAR), Signalisation et physiopathologie cardiaque, Université Paris-Sud - Paris 11 (UP11)-IFR141-Institut National de la Santé et de la Recherche Médicale (INSERM), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-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. |
| المصدر: | ISSN: 1932-6203. |
| بيانات النشر: | CCSD Public Library of Science |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | MESH: Animals, MESH: Cardiotonic Agents/pharmacology, MESH: Signal Transduction, MESH: Viper Venoms/pharmacology, MESH: In Vitro Techniques, MESH: Male, MESH: Mitochondrial Membrane Transport Proteins/drug effects, MESH: Myocardial Infarction/pathology, MESH: Myocardial Reperfusion Injury/prevention & control, MESH: Rats, Wistar, [SDV]Life Sciences [q-bio], [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/27618302; PUBMED: 27618302; PUBMEDCENTRAL: PMC5019389 |
| DOI: | 10.1371/journal.pone.0162632.s006 |
| الاتاحة: | https://riip.hal.science/pasteur-01444516 https://riip.hal.science/pasteur-01444516v1/document https://riip.hal.science/pasteur-01444516v1/file/Lebetin%202,%20a%20Snake%20Venom-Derived%20%281%29.PDF https://doi.org/10.1371/journal.pone.0162632.s006 |
| Rights: | http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.84DB4721 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pone.0162632.s006 |
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