Abstract
The thioredoxin (Txn) system is the most crucial antioxidant defense mechanism in the myocardium, and hampering the Txn system may compromise cell survival. Calcium (Ca) imbalance is associated with a variety of cardiomyopathies, and dysregulation of Ca2+ homeostasis is often considered a critical starting point for heart disease. However, the roles of Txn and the Txn system in maintaining Ca2+ homeostasis in cardiomyocytes have been infrequently reported. Here, we examined the expression of genes associated with Ca2+ channels using a model of Txn suppression in cardiomyocyte cultures (siRNA and Txn inhibitor) and report that Txn knockdown can cause Ca2+ overload in the myocardial cytoplasm and release of endoplasmic reticulum (ER) Ca2+, which induces ER stress. Our results showed that Txn knockdown could lead to cytosolic Ca2+ overload through upregulated gene expression of Ca2+ channel-related genes in the cytoplasmic and ER membranes. Furthermore, we find that excessive Ca2+ concentrations in the cytoplasm may increase myocardial contraction, and heat shock proteins may play a protective role throughout the process. Our present study reveals a novel model of regulation for low Txn expression in myocardial injury.