RESEARCH ARTICLE Catestatin Exerts Direct Protective Effects on Rat Cardiomyocytes Undergoing Ischemia/ Reperfusion by Stimulating PI3K-Akt-GSK3β Pathway and Preserving Mitochondrial Membrane Potential

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 sys-tem, 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 car-diomyocyte 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 phos-pholamban (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 main