title: Activation of Na+/K+-ATPase attenuates high glucose-induced H9c2 cell apoptosis via suppressing ROS accumulation and MAPKs activities by DRm217.
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.
authors: Department of Biochemistry and Molecular Biology, Medical College of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Xiaofei
authors: X
authors: Yan
authors: Department of Immunology and Microbiology, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Meng
authors: M
authors: Xun
authors: Department of Biochemistry and Molecular Biology, Medical College of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Jing
authors: J
authors: Li
authors: Department of Biochemistry and Molecular Biology, Medical College of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Litao
authors: L
authors: Wu
authors: Department of Biochemistry and Molecular Biology, Medical College of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Xiaojuan
authors: X
authors: Dou
authors: Hospital of Nephrology, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, China jzheng@xjtu.edu.cn.
authors: Jin
authors: J
authors: Zheng
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D017382:Reactive Oxygen Species; D020928:Mitogen-Activated Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D002118:Calcium
keywords: DRm217; Na+/K+-ATPase; ROS; high glucose