Liraglutide preserves intracellular calcium handling in isolated murine myocytes exposed to oxidative stress.

摘要

In ischemic/reperfusion (I/R) injured hearts, severe oxidativestress occurs and is associated with intracellular calcium (Ca2+)overload. Glucagon-Like Peptide-1 (GLP-1) analogues have beenshown to exert cardioprotection in I/R heart. However, there islittle information regarding the effects of GLP-1 analogue on theintracellular Ca2+ regulation in the presence of oxidative stress.Therefore, we investigated the effects of GLP-1 analogue,(liraglutide, 10 μM) applied before or after hydrogen peroxide(H2O2, 50 μM) treatment on intracellular Ca2+ regulation inisolated cardiomyocytes. We hypothesized that liraglutide canattenuate intracellular Ca2+ overload in cardiomyocytes underH2O2-induced cardiomyocyte injury. Cardiomyocytes wereisolated from the hearts of male Wistar rats. Isolatedcardiomyocytes were loaded with Fura-2/AM and fluorescenceintensity was recorded. Intracellular Ca2+ transient decay rate,intracellular Ca2+ transient amplitude and intracellular diastolicCa2+ levels were recorded before and after treatment withliraglutide. In H2O2 induced severe oxidative stressedcardiomyocytes (which mimic cardiac I/R) injury, liraglutide givenprior to or after H2O2 administration effectively increased bothintracellular Ca2+ transient amplitude and intracellularCa2+ transient decay rate, without altering the intracellulardiastolic Ca2+ level. Liraglutide attenuated intracellularCa2+ overload in H2O2-induced cardiomyocyte injury and may beresponsible for cardioprotection during cardiac I/R injury bypreserving physiological levels of calcium handling during thesystolic and diastolic phases of myocyte activation.