Galanin receptors activation modulates myocardial metabolic and antioxidant responses to ischaemia/reperfusion stress

Abstract

The neuropeptide galanin comprising 29 amino acid residues (30 in humans) is widely expressed in the central nervous system and peripheral organs and tissues. Galanin exerts its biological activities through three different G protein-coupled receptors, GalR1, GalR2 and GalR3, all of which are found in the heart. 1 Over the past decade, a wealth of data has been accumulated that substantiates targeting galanin receptors for the treatment of various human diseases and pathological conditions, including Alzheimer's disease, metabolic diseases, mood disorders, pain, anxiety and solid tumors. 2 However, the physiological and pharmacological effects of galanin in heart diseases are much less studied. We have recently demonstrated that N-terminal fragments of galanin (2-11) and(2-15) and their chemically modified analogues reduce experimental myocardial I/R injury. 3-5 These peptides increased cell viability, AbstractThe mechanisms of protective action of the neuropeptide galanin and its N-terminal fragments against myocardial ischaemia/reperfusion (I/R) injury remain obscure. The aim of this work was to study effects of a novel peptide agonist of galanin receptors [βAla14, His15]-galanin (2-15) (G1) and the full-length galanin (G2) on energy and antioxidant status of the heart with acute infarction. The peptides were synthesized by the automatic solid phase method using Fmoc technology. Their structure was identified by 1 H-NMR spectroscopy and MALDI-TOF mass spectrometry. Experiments were performed on anaesthetized open-chest rats subjected to myocardial regional ischaemia and reperfusion. Intravenous (iv) administration of optimal doses of peptides G1 and G2 (1.0 and 0.5 mg/kg, respectively, at the onset of reperfusion significantly reduced infarct size (on average by 40% compared with control) and the plasma activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH).These effects were associated with augmented preservation of aerobic energy metabolism, increased activity of Cu,Zn superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and decreased lipid peroxidation in the area at risk (AAR) at the end of reperfusion. Peptide G1 showed more efficient recovery of the majority of metabolic and antioxidant parameters. The results provide evidence that the galaninergic system can be considered a promising target to reduce energy dysregulation and oxidative damage in myocardial I/R injury. K E Y W O R D Santioxidant defence, energy metabolism, galanin, myocardial infarction, necrosis markers, rat

Alarin alleviated cardiac fibrosis via attenuating oxidative stress in heart failure rats

“…Alarin was discovered as an alternate transcript of the GALP gene (Santic et al 2006 , 2007 ), and can be detected in circulating blood (Hu et al 2019 ). It showed that galaninergic system can be considered a promising target to reduce energy dysregulation and attenuate oxidative damage in myocardial injury induced by ischaemia/reperfusion (I/R) of rats (Studneva et al 2019b ). An agonist of galanin receptors GalR1-3 can attenuate doxorubicin-induced cardiotoxicity (Studneva et al 2019a ).…”

Recent advances in mass spectrometry analysis of neuropeptides

“…Cardiac assays have also been performed on mammals. Studneva et al (2019) administered forms of galanin to myocardial injury-induced rats and recorded blood pressure and heart rate in vivo.…”

The effect of lithium tetraborate as a novel cardioprotective agent after renal ischemia-reperfusion injury

“…To eliminate oxidative stress, antioxidants are promising candidates for I/R injury therapy. Thus, it is noteworthy to evaluate the association between the pharmacodynamics effects of antioxidants and I/R injury alleviation (Studneva et al, 2019). Antioxidants inhibit reactive oxygen species (ROS) emission and apoptosis induction (Xiao et al, 2016).…”