Oxidative modification of the cardiac sodium potassium pump is worsened in the absence of FXYD1, contributing to cardiac dysfunction and fibrosis

Introduction FXYD1 is a small membrane protein that endogenously protects the cardiac Na + -K + ATPase from oxidative inhibition. Given the importance of the Na + -K + ATPase in normal cardiac function, we hypothesized that absence of FXYD1 would worsen reactive oxygen species (ROS)-induced cardiac dysfunction. Methods and Results In studies were performed using wild-type (WT) and FXYD1 knockout (KO) mice. FXYD1 KO mice are prone to exacerbated vascular superoxide generation (P + -K + ATPase β1 subunit antibody-coated magnetic beads. Immunoblotting was performed using glutathione antibody and it was found that glutathionylation of the Na + -K + ATPase β1 subunit was increased in Ang II-treated FXYD1 KO mice (P Summary This data defines a new role for FXYD1 in preventing cardiac dysfunction and fibrosis characterized by elevated ROS. Impaired oxidative inhibition of the Na + -K + ATPase β1 subunit plays a likely role in mediating this protective response.