Galanin/GalR1-3 system: A promising therapeutic target for myocardial ischemia/reperfusion injury
N-terminal fragments of galanin (2–11) and (2–15) are critical for binding to GalR1-3 receptors, members of the G-protein-coupled receptor superfamily, and are involved in myocardial protection against ischemia/reperfusion (I/R) injury. This study was designed to synthesize novel GalR1-3 agonists wi...
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doaj-8c7de67e93af4efc868e2271aa231ebf2021-05-21T04:15:51ZengElsevierBiomedicine & Pharmacotherapy0753-33222019-01-0110915561562Galanin/GalR1-3 system: A promising therapeutic target for myocardial ischemia/reperfusion injuryMarina Palkeeva0Irina Studneva1Alexander Molokoedov2Larisa Serebryakova3Oksana Veselova4Michael Ovchinnikov5Maria Sidorova6Oleg Pisarenko7National Medical Research Center for Cardiology, 3rd Cherepkovskaya Str., 15A, 121552, Moscow, Russian FederationNational Medical Research Center for Cardiology, 3rd Cherepkovskaya Str., 15A, 121552, Moscow, Russian FederationNational Medical Research Center for Cardiology, 3rd Cherepkovskaya Str., 15A, 121552, Moscow, Russian FederationNational Medical Research Center for Cardiology, 3rd Cherepkovskaya Str., 15A, 121552, Moscow, Russian FederationNational Medical Research Center for Cardiology, 3rd Cherepkovskaya Str., 15A, 121552, Moscow, Russian FederationNational Medical Research Center for Cardiology, 3rd Cherepkovskaya Str., 15A, 121552, Moscow, Russian FederationNational Medical Research Center for Cardiology, 3rd Cherepkovskaya Str., 15A, 121552, Moscow, Russian FederationCorresponding author at: Laboratory for Myocardial Metabolism, National Medical Research Center for Cardiology, 121552 Moscow, Russian Federation.; National Medical Research Center for Cardiology, 3rd Cherepkovskaya Str., 15A, 121552, Moscow, Russian FederationN-terminal fragments of galanin (2–11) and (2–15) are critical for binding to GalR1-3 receptors, members of the G-protein-coupled receptor superfamily, and are involved in myocardial protection against ischemia/reperfusion (I/R) injury. This study was designed to synthesize novel GalR1-3 agonists with improved properties and evaluate their efficiency as cardioprotective agents. Peptide agonists were synthesized by the automatic solid phase method using Fmoc technology and purified by preparative HPLC. Their chemical structure was identified by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Novel ligands of galanin receptors have greater solubility in water than natural galanin fragments. Cardiac function indices, myocardial infarct size and plasma activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) were measured to assess the peptide bioactivity. Infusion of optimal concentrations of the peptides (210–240 μM) after global ischemia enhanced functional recovery of isolated rat heart during reperfusion. Intravenous administration of the peptides in a dose range of 1–2 mg/kg at the onset of reperfusion significantly reduced infarct size and plasma levels of CK-MB and LDH in rats in vivo. The chimeric ligand [βAla14, His15]-galanin (2–15) exhibited the most beneficial effect on both models of I/R injury. The results suggest that pharmacological agonists of GalR1-3 receptors can be a rational basis for drug developments in the field of cardiovascular diseases.http://www.sciencedirect.com/science/article/pii/S0753332218335637Modified galanin fragmentsMyocardial ischemia/reperfusion injuryRatMyocardial protection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marina Palkeeva Irina Studneva Alexander Molokoedov Larisa Serebryakova Oksana Veselova Michael Ovchinnikov Maria Sidorova Oleg Pisarenko |
spellingShingle |
Marina Palkeeva Irina Studneva Alexander Molokoedov Larisa Serebryakova Oksana Veselova Michael Ovchinnikov Maria Sidorova Oleg Pisarenko Galanin/GalR1-3 system: A promising therapeutic target for myocardial ischemia/reperfusion injury Biomedicine & Pharmacotherapy Modified galanin fragments Myocardial ischemia/reperfusion injury Rat Myocardial protection |
author_facet |
Marina Palkeeva Irina Studneva Alexander Molokoedov Larisa Serebryakova Oksana Veselova Michael Ovchinnikov Maria Sidorova Oleg Pisarenko |
author_sort |
Marina Palkeeva |
title |
Galanin/GalR1-3 system: A promising therapeutic target for myocardial ischemia/reperfusion injury |
title_short |
Galanin/GalR1-3 system: A promising therapeutic target for myocardial ischemia/reperfusion injury |
title_full |
Galanin/GalR1-3 system: A promising therapeutic target for myocardial ischemia/reperfusion injury |
title_fullStr |
Galanin/GalR1-3 system: A promising therapeutic target for myocardial ischemia/reperfusion injury |
title_full_unstemmed |
Galanin/GalR1-3 system: A promising therapeutic target for myocardial ischemia/reperfusion injury |
title_sort |
galanin/galr1-3 system: a promising therapeutic target for myocardial ischemia/reperfusion injury |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2019-01-01 |
description |
N-terminal fragments of galanin (2–11) and (2–15) are critical for binding to GalR1-3 receptors, members of the G-protein-coupled receptor superfamily, and are involved in myocardial protection against ischemia/reperfusion (I/R) injury. This study was designed to synthesize novel GalR1-3 agonists with improved properties and evaluate their efficiency as cardioprotective agents. Peptide agonists were synthesized by the automatic solid phase method using Fmoc technology and purified by preparative HPLC. Their chemical structure was identified by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Novel ligands of galanin receptors have greater solubility in water than natural galanin fragments. Cardiac function indices, myocardial infarct size and plasma activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) were measured to assess the peptide bioactivity. Infusion of optimal concentrations of the peptides (210–240 μM) after global ischemia enhanced functional recovery of isolated rat heart during reperfusion. Intravenous administration of the peptides in a dose range of 1–2 mg/kg at the onset of reperfusion significantly reduced infarct size and plasma levels of CK-MB and LDH in rats in vivo. The chimeric ligand [βAla14, His15]-galanin (2–15) exhibited the most beneficial effect on both models of I/R injury. The results suggest that pharmacological agonists of GalR1-3 receptors can be a rational basis for drug developments in the field of cardiovascular diseases. |
topic |
Modified galanin fragments Myocardial ischemia/reperfusion injury Rat Myocardial protection |
url |
http://www.sciencedirect.com/science/article/pii/S0753332218335637 |
work_keys_str_mv |
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