Abstract
Background and purposeGalanin is an endogenous peptide involved in diverse physiological functions in the central nervous system including central cardiovascular regulation. The present study was designed to evaluate the potential effects of the short N-terminal galanin fragment 2-15 (G) on cardiac ischemia/reperfusion (I/R) injury.Experimental ApproachPeptide G was synthesized by the automatic solid phase method and identified by 1H-NMR spectroscopy and mass spectrometry. Experiments were performed on cultured rat cardiomyoblast (H9C2) cells, isolated perfused working rat hearts and anaesthetized open-chest rats.Key ResultsCell viability increased significantly after treatment with 10 and 50 nM of G peptide. In hypoxia and reoxygenation conditions, exposure of H9C2 cells to G peptide decreased cell apoptosis and mitochondrial reactive oxygen species (ROS) production. Postischemic infusion of G peptide reduced cell membrane damage and improved functional recovery in isolated hearts during reperfusion. These effects were accompanied by enhanced restoration of myocardial metabolic state. Treatment with G peptide at the onset of reperfusion induced minor changes in hemodynamic variables but significantly reduced infarct size and plasma levels of necrosis markers.Conclusion and implicationsThese findings suggest that G peptide is effective in mitigating cardiac I/R injury, thereby providing a rationale for promising tool for the treatment of cardiovascular diseases.
Highlights
Galanin, a 29/30 amino acid neuropeptide, is widely distributed throughout the central and peripheral nervous system as well as endocrine system, preferentially in brain, hypothalamus, pituitary, and other tissues including the heart
Treatment with G peptide at the onset of reperfusion induced minor changes in hemodynamic variables but significantly reduced infarct size and plasma levels of necrosis markers. These findings suggest that G peptide is effective in mitigating cardiac I/R injury, thereby providing a rationale for promising tool for the treatment of cardiovascular diseases
GalR1 and GalR3 activate the intracellular effectors through pertussis toxin (PTX) sensitive Gi/o proteins, which results in the inhibition of adenylyl cyclase activity and a decrease in cAMP in the cytosol that leads to the opening of G protein gated inwardly-rectifying potassium (GIRK) channels [4, 5]
Summary
A 29/30 amino acid neuropeptide, is widely distributed throughout the central and peripheral nervous system as well as endocrine system, preferentially in brain, hypothalamus, pituitary, and other tissues including the heart. GalR1 activation stimulates MAPK activity in a PKC-independent manner by coupling with a Gi-type G-protein via Gβγ subunits [6]. GalR2 triggers PLC activity via Gαq/11-proteins, leading to IP3-mediated opening of Ca2+-dependent channels and release of Ca2+ into the cytoplasm from intracellular stores [7]. GalR2 activation inhibits forskolin stimulated cAMP production in a PTX-sensitive manner, suggesting the activation of Gαi/αo-proteins [8]. Activation of all galanin receptors can inhibit the formation of the transcription factor cAMP regulatory element binding protein (CREB) [8]. Galanin is an endogenous peptide involved in diverse physiological functions in the central nervous system including central cardiovascular regulation. Experiments were performed on cultured rat cardiomyoblast (H9C2) cells, isolated perfused working rat hearts and anaesthetized open-chest rats
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