Dataset Information

Myocardial protection from ischemia/reperfusion injury by exogenous galanin fragment.

ABSTRACT:

Background and purpose

Galanin is a multifunctional neuropeptide with pleiotropic roles. The present study was designed to evaluate the potential effects of galanin (2-11) (G1) on functional and metabolic abnormalities in response to myocardial ischemia-reperfusion (I/R) injury.

Experimental approach

Peptide G1 was synthesized by the 9-fluorenylmethoxycarbonyl (Fmoc)-based solid-phase method. The chemical structure was identified by 1H-NMR spectroscopy and mass spectrometry. Experiments were conducted using a rat model of I/R injury in vivo, isolated perfused rat hearts ex vivo and cultured rat cardiomyoblast H9C2 cells in vitro. Cardiac function, infarct size, myocardial energy metabolism, hemodynamic parameters, plasma levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) were measured in order to evaluate the effects of G1 on myocardial I/R injury.

Key results

Treatment with G1 increased cell viability in a dose-dependent manner, inhibited cell apoptosis and excessive mitochondrial reactive oxygen species (ROS) production in response to oxidative stress in H9C2 cells. Pre- or postischemic infusion of G1 enhanced functional and metabolic recovery during reperfusion of the ischemic isolated rat heart. Administration of G1 at the onset of reperfusion significantly reduced infarct size and plasma levels of CK-MB and LDH in rats subjected to myocardial I/R injury.

Conclusions and implications

These data provide the first evidence for cardioprotective activity of galanin G1 against myocardial I/R injury. Therefore, peptide G1 may represent a promising treatment strategy for ischemic heart disease.

SUBMITTER: Timotin A

PROVIDER: S-EPMC5400580 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

Myocardial protection from ischemia/reperfusion injury by exogenous galanin fragment.

Timotin Andrei A Pisarenko Oleg O Sidorova Maria M Studneva Irina I Shulzhenko Valentin V Palkeeva Marina M Serebryakova Larisa L Molokoedov Aleksander A Veselova Oksana O Cinato Mathieu M Tronchere Helene H Boal Frederic F Kunduzova Oksana O

Oncotarget 20170301 13

<h4>Background and purpose</h4>Galanin is a multifunctional neuropeptide with pleiotropic roles. The present study was designed to evaluate the potential effects of galanin (2-11) (G1) on functional and metabolic abnormalities in response to myocardial ischemia-reperfusion (I/R) injury.<h4>Experimental approach</h4>Peptide G1 was synthesized by the 9-fluorenylmethoxycarbonyl (Fmoc)-based solid-phase method. The chemical structure was identified by 1H-NMR spectroscopy and mass spectrometry. Exper ...[more]

PMID: 28177906

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Project description:Myocardial ischemia-reperfusion (I/R) results in the generation of free radicals, accumulation of lipid peroxidation-derived unsaturated aldehydes, variable angina (pain), and infarction. The transient receptor potential ankyrin 1 (TRPA1) mediates pain signaling and is activated by unsaturated aldehydes, including acrolein and 4-hydroxynonenal. The contribution of TRPA1 (a Ca2+-permeable channel) to I/R-induced myocardial injury is unknown. We tested the hypothesis that cardiac TRPA1 confers myocyte sensitivity to aldehyde accumulation and promotes I/R injury. Although basal cardiovascular function in TRPA1-null mice was similar to that in wild-type (WT) mice, infarct size was significantly smaller in TRPA1-null mice than in WT mice (34.1?±?9.3 vs. 14.3?±?9.9% of the risk region, n = 8 and 7, respectively, P < 0.05), despite a similar I/R-induced area at risk (40.3?±8.4% and 42.2?±?11.3% for WT and TRPA1-null mice, respectively) after myocardial I/R (30 min of ischemia followed by 24 h of reperfusion) in situ. Positive TRPA1 immunofluorescence was present in murine and human hearts and was colocalized with connexin43 at intercalated disks in isolated murine cardiomyocytes. Cardiomyocyte TRPA1 was confirmed by quantitative RT-PCR, DNA sequencing, Western blot analysis, and electrophysiology. A role of TRPA1 in cardiomyocyte toxicity was demonstrated in isolated cardiomyocytes exposed to acrolein, an I/R-associated toxin that induces Ca2+ accumulation and hypercontraction, effects significantly blunted by HC-030031, a TRPA1 antagonist. Protection induced by HC-030031 was quantitatively equivalent to that induced by SN-6, a Na+/Ca2+ exchange inhibitor, further supporting a role of Ca2+ overload in acrolein-induced cardiomyocyte toxicity. These data indicate that cardiac TRPA1 activation likely contributes to I/R injury and, thus, that TRPA1 may be a novel therapeutic target for decreasing myocardial I/R injury. NEW & NOTEWORTHY Transient receptor potential ankyrin 1 (TRPA1) activation mediates increased blood flow, edema, and pain reception, yet its role in myocardial ischemia-reperfusion (I/R) injury is unknown. Genetic ablation of TRPA1 significantly decreased myocardial infarction after I/R in mice. Functional TRPA1 in cardiomyocytes was enriched in intercalated disks and contributed to acrolein-induced Ca2+ overload and hypercontraction. These data indicate that I/R activation of TRPA1 worsens myocardial infarction; TRPA1 may be a potential target to mitigate I/R injury.

Dataset Information

Myocardial protection from ischemia/reperfusion injury by exogenous galanin fragment.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

Myocardial protection from ischemia/reperfusion injury by exogenous galanin fragment.

Similar Datasets

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