Catestatin Exerts Direct Protective Effects on Rat Cardiomyocytes Undergoing Ischemia/Reperfusion by Stimulating PI3K-Akt-GSK3β Pathway and Preserving Mitochondrial Membrane Potential
| Autor: | Saveria Femminò, Renzo Levi, Maria Pia Gallo, Giuseppe Alloatti, Bruno Tota, Sara Fornero, Clara Gallina, Eleonora Bassino |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Cell Survival lcsh:Medicine Myocardial Reperfusion Injury Pharmacology Biology Nitric oxide Wortmannin chemistry.chemical_compound Glycogen Synthase Kinase 3 Phosphatidylinositol 3-Kinases Internal medicine medicine Animals Myocytes Cardiac Viability assay Propidium iodide lcsh:Science Inner mitochondrial membrane Protein kinase B PI3K/AKT/mTOR pathway Membrane Potential Mitochondrial Multidisciplinary lcsh:R Peptide Fragments Phospholamban Rats Endocrinology chemistry Chromogranin A lcsh:Q human activities Proto-Oncogene Proteins c-akt Research Article Signal Transduction |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 3, p e0119790 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Catestatin (Cst) is a 21-amino acid peptide deriving from Chromogranin A. Cst exerts an overall protective effect against an excessive sympathetic stimulation of cardiovascular system, being able to antagonize catecholamine secretion and to reduce their positive inotropic effect, by stimulating the release of nitric oxide (NO) from endothelial cells. Moreover, Cst reduces ischemia/reperfusion (I/R) injury, improving post-ischemic cardiac function and cardiomyocyte survival. To define the cardioprotective signaling pathways activated by Cst (5 nM) we used isolated adult rat cardiomyocytes undergoing simulated I/R. We evaluated cell viability rate with propidium iodide labeling and mitochondrial membrane potential (MMP) with the fluorescent probe JC-1. The involvement of Akt, GSK3β, eNOS and phospholamban (PLN) cascade was studied by immunofluorescence. The role of PI3K-Akt/NO/cGMP pathway was also investigated by using the pharmacological blockers wortmannin (Wm), L-NMMA and ODQ. Our experiments revealed that Cst increased cell viability rate by 65% and reduced cell contracture in I/R cardiomyocytes. Wm, L-NMMA and ODQ limited the protective effect of Cst. The protective outcome of Cst was related to its ability to maintain MMP and to increase AktSer473, GSK3βSer9, PLNThr17 and eNOSSer1179 phosphorylation, while treatment with Wm abolished these effects. Thus, the present results show that Cst is able to exert a direct action on cardiomyocytes and give new insights into the molecular mechanisms involved in its protective effect, highlighting the PI3K/NO/cGMP pathway as the trigger and the MMP preservation as the end point of its action. |
| Databáze: | OpenAIRE |
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