DRm217 attenuates myocardial ischemia-reperfusion injury via stabilizing plasma membrane Na+-K+-ATPase, inhibiting Na+-K+-ATPase/ROS pathway and activating PI3K/Akt and ERK1/2

Abstract

Na+-K+-ATPase has close relationship with myocardial ischemia/reperfusion (IR) injury. Activation of Na+-K+-ATPase with its DR region specific antibody produces cardioprotective effect. In this study, we aimed to explore whether DRm217, a proved DR region specific antibody, could protect myocardial cells against IR injury and uncover the mechanisms under it. By employing H9c2 myocardial cell and SD rat, we found that DRm217 protected cardiac cells against IR-induced cell injury and apoptosis. DRm217 produced protective effect via stabilizing Na+-K+-ATPase membrane expression and inhibiting Na+-K+-ATPase/Src/NADPH oxidase dependent ROS accumulation. PI3K/Akt and ERK1/2 participated in DRm217-induced cardiomyocyte survival, but not in DRm217-related ROS reduction. Therefore, DRm217 can be used as a potential cardioprotective adjuvant in myocardial IR therapy and interference of Na+-K+-ATPase/ROS pathway will be a promising modality for clinical myocardial IR therapy.