Selenoprotein Gpx3 knockdown induces myocardial damage through Ca2+ leaks in chickens†
Glutathione peroxidase 3 (Gpx3) is a pivotal selenoprotein that acts as an antioxidant. However, the role of Gpx3 in maintaining the normal metabolism of cardiomyocytes remains to be elucidated in more detail. Herein, we employed a model of Gpx3 interference in chicken embryos in vivo and Gpx3 knockdown chicken cardiomyocytes in vitro. Real-time PCR, western blotting and fluorescent staining were performed to detect reactive oxygen species (ROS), the calcium (Ca2+) concentration, endoplasmic reticulum (ER) stress, myocardial contraction, inflammation and heat shock proteins (HSPs). Our results revealed that Gpx3 suppression increased the level of ROS, which induced Ca2+ leakage in the cytoplasm by blocking the expression of Ca2+ channels. The imbalance of Ca2+ homeostasis triggered ER stress and blocked myocardial contraction. Furthermore, we found that Ca2+ imbalance in the cytoplasm induced severe inflammation, and HSPs might play a protective role throughout these processes. In conclusion, Gpx3 suppression induces myocardial damage through the activation of Ca2+-dependent ER stress.