Activation of Na+/K+-ATPase attenuates high glucose-induced H9c2 cell apoptosis via suppressing ROS accumulation and MAPKs activities by DRm217

• Published in: Acta biochimica et biophysica Sinica Vol. 48; no. 10; pp. 883 - 893
• Main Authors: Yan, Xiaofei, Xun, Meng, Li, Jing, Wu, Litao, Dou, Xiaojuan, Zheng, Jin
• Format: Journal Article
• Language: English
• Published: China 01-10-2016
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Apoptosis - drug effects; Blotting, Western; Calcium - metabolism; Cell Line; Cell Survival - drug effects; Dose-Response Relationship, Drug; Female; Glucose - pharmacology; Mice, Inbred BALB C; Microscopy, Fluorescence; Mitogen-Activated Protein Kinases - metabolism; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Phosphorylation - drug effects; Rats; Reactive Oxygen Species - metabolism; Sodium-Potassium-Exchanging ATPase - immunology; Sodium-Potassium-Exchanging ATPase - metabolism; high glucose; Na+/K+-ATPase; DRm217; ROS
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmw079

Hyperglycemia is one of the major factors responsible for the myocardial apoptosis and dysfunction in diabetes. Many studies have proved that there is a close relationship between decreased Na
/K
-ATPase activity and diabetic cardiomyopathy. However, the effect of directly activated Na
/K
-ATPase on high glucose-induced myocardial injury is still unknown. Here we found that DRm217, a Na
/K
-ATPase's DR-region specific monoclonal antibody and direct activator, could prevent high glucose-induced H9c2 cell injury, reactive oxygen species (ROS) release, and mitochondrial dysfunction. High glucose-treatment decreased Na
/K
-ATPase activity and increased intracellular Ca
level, whereas DRm217 increased Na
/K
-ATPase activity and alleviated Ca
overload. Inhibition of Ca
overload or closing sodium calcium exchanger (NCX channel) could reverse high glucose-induced ROS increasing and cell injury. In addition, DRm217 could significantly attenuate high glucose-induced p38, JNK and ERK1/2 phosphorylation, which were involved in high glucose-induced cell injury and ROS accumulation. Our findings suggest that DRm217 may protect against the deleterious effects of high glucose in the heart. Prevention of high glucose-induced myocardial cell injury by specific Na
/K
-ATPase activator may be an attractive therapeutic option.