학술논문
Activation of Na.sup.+-K.sup.+-ATPase with DRm217 attenuates oxidative stress-induced myocardial cell injury via closing Na.sup.+-K.sup.+-ATPase/Src/Ros amplifier
Article
Article
Document Type
Academic Journal
Author
Source
Apoptosis - An International Journal on Programmed Cell Death. April 2017, Vol. 22 Issue 4, p531, 13 p.
Subject
Language
English
ISSN
1360-8185
Abstract
Author(s): Xiaofei Yan [sup.1], Meng Xun [sup.2], Xiaojuan Dou [sup.1], Litao Wu [sup.1], Fujun Zhang [sup.1], Jin Zheng [sup.3] Author Affiliations: (1) 0000 0001 0599 1243, grid.43169.39, Department of Biochemistry [...]
Reduced Na.sup.+-K.sup.+-ATPase activity has close relationship with cardiomyocyte death. Reactive oxygen species (ROS) also plays an important role in cardiac cell damage. It has been proved that Na.sup.+-K.sup.+-ATPase and ROS form a feed-forward amplifier. The aim of this study was to explore whether DRm217, a proved Na.sup.+/K.sup.+-ATPase's DR-region specific monoclonal antibody and direct activator, could disrupt Na.sup.+-K.sup.+-ATPase/ROS amplifier and protect cardiac cells from ROS-induced injury. We found that DRm217 protected myocardial cells against hydrogen peroxide (H.sub.2O.sub.2)-induced cardiac cell injury and mitochondrial dysfunction. DRm217 also alleviated the effect of H.sub.2O.sub.2 on inhibition of Na.sup.+-K.sup.+-ATPase activity, Na.sup.+-K.sup.+-ATPase cell surface expression, and Src phosphorylation. H.sub.2O.sub.2-treatment increased intracellular ROS, mitochondrial ROS and induced intracellular Ca.sup.2+, mitochondrial Ca.sup.2+ overload. DRm217 closed Na.sup.+-K.sup.+-ATPase/ROS amplifier, alleviated Ca.sup.2+ accumulation and finally inhibited ROS and mitochondrial ROS generation. These novel results may help us to understand the important role of the Na.sup.+-K.sup.+-ATPase in oxidative stress and oxidative stress-related disease.
Reduced Na.sup.+-K.sup.+-ATPase activity has close relationship with cardiomyocyte death. Reactive oxygen species (ROS) also plays an important role in cardiac cell damage. It has been proved that Na.sup.+-K.sup.+-ATPase and ROS form a feed-forward amplifier. The aim of this study was to explore whether DRm217, a proved Na.sup.+/K.sup.+-ATPase's DR-region specific monoclonal antibody and direct activator, could disrupt Na.sup.+-K.sup.+-ATPase/ROS amplifier and protect cardiac cells from ROS-induced injury. We found that DRm217 protected myocardial cells against hydrogen peroxide (H.sub.2O.sub.2)-induced cardiac cell injury and mitochondrial dysfunction. DRm217 also alleviated the effect of H.sub.2O.sub.2 on inhibition of Na.sup.+-K.sup.+-ATPase activity, Na.sup.+-K.sup.+-ATPase cell surface expression, and Src phosphorylation. H.sub.2O.sub.2-treatment increased intracellular ROS, mitochondrial ROS and induced intracellular Ca.sup.2+, mitochondrial Ca.sup.2+ overload. DRm217 closed Na.sup.+-K.sup.+-ATPase/ROS amplifier, alleviated Ca.sup.2+ accumulation and finally inhibited ROS and mitochondrial ROS generation. These novel results may help us to understand the important role of the Na.sup.+-K.sup.+-ATPase in oxidative stress and oxidative stress-related disease.