Myocardial protection from ischemia/reperfusion injury by exogenous galanin fragment

Timotin, Andreï; Писаренко, О. И.; Sidorova, M. V.; Студнева, И. М.; Shulzhenko, V. S.; Palkeeva, M. E.; Serebryakova, L. I.; Молокоедов, А. С.; Veselova, Oksana; Cinato, Mathieu; Tronchère, Hélène; Boal, Frédéric; Kunduzova, Oksana

doi:10.18632/oncotarget.15071

Cited by 38 publications

(30 citation statements)

References 40 publications

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“…3 The N-terminal part is a fragment of galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) and the C-terminal part is the other bioactive dipeptide L-carnosine capable of scavenging hydroxyl radicals (Table 1). 6 A fragment of galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) contains residues Trp, 2 Asn, 5 Gly 8 and Tyr, 9 which are necessary for interaction of the peptide with the GalR2 receptor 7,8 and thereby to trigger cardioprotective effects. L-carnosine tailing to C-terminal part of peptide G1 enhances its resistance to the action of exopeptidases due to the insertion of βAla14.…”

Section: Structure and Properties F Of Peptide G1mentioning

confidence: 99%

“…24 The shift in the balance between ROS formation and antioxidant protection in favour of the first leads to redox imbalance, oxidative stress and an increase in cell damage. A loss of antioxidant enzymes activities in our experiments could be associated with both the harmful effects of ROS and leakage of antioxidant enzymes into the extracellular fluid.It was previously shown that treatment of rat myocardial H9C2 cells with galanin fragments (2-11) and (2-15) significantly reduced mitochondrial superoxide production in response to oxidative stress 4,5. Intravenous administration of full-length galanin to mice with myocardial I/R injury caused a similar effect 25.…”

mentioning

confidence: 92%

“…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][4][5] These peptides increased cell viability,…”

mentioning

confidence: 98%

“…Post-ischaemic administration of the peptides improved functional recovery of isolated perfused rat hearts and reduced infarct size in rats in vivo. 4,5 The chimeric ligand [βAla14, His15]-galanin (2-15) (G1), which is composed of galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) and the dipeptide carnosine, exhibited the most beneficial effect. 3 The mechanisms of action of peptide G1 remain unclear.…”

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confidence: 99%

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

Студнева

Serebryakova

Veselova

et al. 2019

Clin Exp Pharma Physio

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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

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Section: Structure and Properties F Of Peptide G1mentioning

confidence: 99%

mentioning

confidence: 92%

mentioning

confidence: 98%

mentioning

confidence: 99%

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

Студнева

Serebryakova

Veselova

et al. 2019

Clin Exp Pharma Physio

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“…Cardiomyocyte death due to ischemia/reperfusion (I/R) injury is well-known to increase morbidity, mortality and medical cost in patients with ischemic heart disease [1][2][3][4]. Treatment for this myocardial ischemia-reperfusion disorder and cardiomyocyte death has had limited success.…”

Section: Introductionmentioning

confidence: 99%

Altered myocardial gene expression profiling in the ischemic tissues at different time points after cardiac ischemia/reperfusion in rats

Li¹,

Lin²,

He³

et al. 2018

Oncotarget

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We used Agilent Gene Expression microarray to analyze differential gene and lncRNA expression patterns in the myocardial ischemia regions during ischemia/ reperfusion (I/R)-induced cardiac injury in rats. Male SD rats were assigned into control group, 2 h group (30 min ischemia followed by 2 h reperfusion), 0.5 h (30 min ischemia followed by 0.5h reperfusion) group. We observed that of 18090 lncRNAs, an average of 233 lncRNAs was up-regulated in ischemic tissues of 2 h group, compared with those in control group, while an average of 6115 lncRNAs was down-regulated (with a > 2.0 fold-change and p < 0.05). Further, a total of 3135 mRNAs were differentially expressed between control group and 2h group, in which 542 mRNAs were up-regulated and 2593 mRNAs were down-regulated. Some differentially expressed genes were validated by qRT-PCR analyses of select lncRNAs in different time points after cardiac I/R injury. We unveiled that the expressions of lncRNA XR_345533.2, NONRATT025386, NONRATT024318, XR_599241.1, and NONRATT025509 were significantly up-regulated in 2h group compared with control group and 0.5h group, whereas the expression of lncRNA NR_130708.1 was downregulated after cardiac I/R injury and had no statistically different between 0.5h group and 2h group. Otherwise, the expressions of lncRNA NONRATT028627, NONRATT021959, XR_590005.1 and NONRATT023191 were significantly up-regulated in 2h group compared with 0.5h group. These findings provide evidence for differential expression patterns of mRNAs and lncRNAs in the ischemic tissues after cardiac I/R injury in rats.

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

Ding

et al. 2021

Amino Acids

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The present study was to explore whether alarin could alleviate heart failure (HF) and attenuate cardia fibrosis via inhibiting oxidative stress. The fibrosis of cardiac fibroblasts (CFs) was induced by angiotensin (Ang) II. HF models were induced by ligation of the left anterior descending artery to cause ischemia myocardial infarction (MI) in Sprague–Dawley rats. Alarin (1.0 nM/kg/d) was administrated by intraperitoneal injection for 28 days. The decreases of left ventricular (LV) ejection fraction (EF), fractional shortening (FS), the maximum of the first differentiation of LV pressure (LV ± dp/dtmax) and LV systolic pressure (LVSP), and the increases of LV volume in systole (LVVS), LV volume in diastole (LVVD), LV end-systolic diameter (LVESD) and LV end-diastolic diameter (LVEDD) in MI rats were improved by alarin treatment. The increases in the expression levels of collagen I, collagen III, and transforming growth factor (TGF)-β were inhibited by alarin treatment in CFs and in the hearts of MI rats. The levels of NADPH oxidase (Nox) activity, superoxide anions and malondialdehyde (MDA) levels were increased, and the level of superoxide dismutase (SOD) activity was reduced in Ang II-treated CFs, which were reversed by alarin. Nox1 overexpression reversed the effects of alarin on attenuating the increases of collagen I, collagen III and TGF-β expression levels induced by Ang II in CFs. These results indicated that alarin improved HF and cardiac fibrosis via inhibiting oxidative stress in HF rats. Nox1 played important roles in the regulation of alarin effects on attenuating CFs fibrosis induced by Ang II.

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Myocardial protection from ischemia/reperfusion injury by exogenous galanin fragment

Cited by 38 publications

References 40 publications

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

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

Altered myocardial gene expression profiling in the ischemic tissues at different time points after cardiac ischemia/reperfusion in rats

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

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