Abstract
 
Vol 48 No. 10: 883-893 [PDF] [Full Text]
 
Activation of Na+/K+-ATPase attenuates high glucose-induced H9c2 cell apoptosis via suppressing ROS accumulation and MAPKs activities by DRm217
 
Xiaofei Yan1, Meng Xun2, Jing Li1, Litao Wu1, Xiaojuan Dou1 and Jin Zheng3,*

1Department of Biochemistry and Molecular Biology, Medical College of Xi'an Jiaotong University, Xi'an 710061, China
2Department of Immunology and Microbiology, Health Science center, Xi'an Jiaotong University, Xi'an 710061, China
3Hospital of Nephrology, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, China
 

Abstract  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 Ca2+ level, whereas DRm217 increased Na+/K+-ATPase activity and alleviated Ca2+ overload. Inhibition of Ca2+ 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.

 

Keywords   Na+/K+-ATPase; high glucose; DRm217; ROS

 

Received   2016-3-11  
Accepted  
2016-5-23

 

Funding  This work was supported by the grants from the National Natural Science Foundation of China (No. 81400232), China Postdoctoral Science Foundation (No. 2015M572571), Fundamental Research Funds for the Central Universities (No. xjtu-2015gjhz17) and the Natu

 

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