Introduction: Catestatin (CST) is a 21-amino acid peptide deriving from chromogranin A (CgA). In mammalian heart, CgA is stored in non-adrenergic myoendocrine atrial cells in association with atrial natriuretic peptide, in Purkinje fibers and in both atrial and ventricular cells. CST antagonizes catecholamine secretion and exerts negative myocardial inotropism, acting via a nitric oxide-dependent mechanism. We have recently demonstrated that CST reduces ischemia/reperfusion (I/R) injury, improving post-ischemic cardiac function and cardiomyocyte survival. Aims: To define the cardioprotective signaling pathways activated by CST on isolated adult rat cardiomyocytes, 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 and phospholamban (PLN) cascade was studied by immunofluorescence. The role of PI3K-Akt pathway was investigated by using the pharmacological blocker wortmannin (Wm). Results: In isolated cardiomyocytes undergoing simulated I/R, CST increased cell viability rate by 65%. The protective effect of CST was related to its ability to maintain MMP and to increase Akt, PLN and GSK3β phosphorylation. Wm abolished CST-induced cardioprotection. Conclusions: These results give new insights into the molecular mechanisms involved in the protective role of CST, highlighting the PI3K pathway as the trigger and the MMP preservation as the end point of its action.
Catestatin-induced cardioprotection involves a PI3K-Akt-GSK3ß pathway converging on mitochondrial membrane potential preservation
BASSINO, ELEONORA;FORNERO, SARA;GALLO, Maria Pia;LEVI, Renzo;ALLOATTI, Giuseppe
2011-01-01
Abstract
Introduction: Catestatin (CST) is a 21-amino acid peptide deriving from chromogranin A (CgA). In mammalian heart, CgA is stored in non-adrenergic myoendocrine atrial cells in association with atrial natriuretic peptide, in Purkinje fibers and in both atrial and ventricular cells. CST antagonizes catecholamine secretion and exerts negative myocardial inotropism, acting via a nitric oxide-dependent mechanism. We have recently demonstrated that CST reduces ischemia/reperfusion (I/R) injury, improving post-ischemic cardiac function and cardiomyocyte survival. Aims: To define the cardioprotective signaling pathways activated by CST on isolated adult rat cardiomyocytes, 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 and phospholamban (PLN) cascade was studied by immunofluorescence. The role of PI3K-Akt pathway was investigated by using the pharmacological blocker wortmannin (Wm). Results: In isolated cardiomyocytes undergoing simulated I/R, CST increased cell viability rate by 65%. The protective effect of CST was related to its ability to maintain MMP and to increase Akt, PLN and GSK3β phosphorylation. Wm abolished CST-induced cardioprotection. Conclusions: These results give new insights into the molecular mechanisms involved in the protective role of CST, highlighting the PI3K pathway as the trigger and the MMP preservation as the end point of its action.
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