Abstract
Atrial fibrillation (AF) is a complex disease with multiple inter-relating causes culminating in rapid atrial activation and atrial structural remodeling. The contribution of endoplasmic reticulum and mitochondria stress to AF has been highlighted. As the class III antiarrhythmic agent, ibutilide are widely used to AF. This study was designed to explore whether ibutilide could treat AF by inhibiting endoplasmic reticulum stress pathways and mitochondria stress. The neonatal rat cardiomyocytes were isolated and exposed to H2O2, ibutilide was add to the culture medium 12 h. Then the cell viability, oxidative stress levels and apoptotic rate were analyzed. In addition, endoplasmic reticulum stress related protein (GRP78, GRP94, CHOP), mitochondria-dependent protein (Bax, Bcl-2) and caspase-3/9/12 were identified by real-time PCR and western blot analysis. In our results, remarkable decreased cell viability and oxidative stress levels were detected in cardiomyocytes after treating with H2O2. The apoptotic rate and the expression of proteins involved in mitochondrial stress and endoplasmic reticulum stress pathways increased. While ibutilide significantly inhibited these changes. These data suggested that ibutilide serves a protective role against H2O2-induced apoptosis of neonatal rat cardiomyocytes, and the mechanism is related to suppression of mitochondrial stress and endoplasmic reticulum stress.
Highlights
Atrial fibrillation (AF) is the most serious cardiovascular disease in the world [1]
Production of reactive oxygen species (ROS) has been linked to endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), ROS plays a critical role in many cellular processes and can be produced in the cytosol and several organelles, including the ER and mitochondria [6]
The results showed that the effect of ibutilide on neonatal rat cardiomyocytes emerged bi-directional with the concentration increase of ibutilide
Summary
Atrial fibrillation (AF) is the most serious cardiovascular disease in the world [1]. Because of aging of the population and improved survival of patients with other cardiovascular diseases, the prevalence of AF is increasing during the past few decades. Production of ROS has been linked to ER stress and the unfolded protein response (UPR), ROS plays a critical role in many cellular processes and can be produced in the cytosol and several organelles, including the ER and mitochondria [6]. Their relationship in neonatal rat cardiomyocytes is not clear
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