Activation of Na+-K+-ATPase with DRm217 attenuates oxidative stress-induced myocardial cell injury via closing Na+-K+-ATPase/Src/Ros amplifier
Activation of Na+-K+-ATPase with DRm217 attenuates oxidative stress-induced myocardial cell injury via closing Na+-K+-ATPase/Src/Ros amplifier
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DRm217 激活 Na -K -ATP 酶通过关闭 Na -K -ATP 酶/Src/Ros 放大器减轻氧化应激诱导的心肌细胞损伤
DOI：
10.1007/s10495-016-1342-2
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发表时间：
2017-02
期刊：
影响因子：
7.2
通讯作者：
Zheng Jin
中科院分区：
文献类型：
--
作者：
Yan Xiaofei;Xun Meng;Dou Xiaojuan;Wu Litao;Zhang Fujun;Zheng Jin
Na+-K+-ATP酶活性降低与心肌细胞死亡密切相关。活性氧（ROS）在心肌细胞损伤中也起着重要作用。研究表明，Na ~+-K ~+-ATP酶与活性氧形成前馈放大器。本研究旨在探讨Na+/K+-ATP酶DR区特异性单克隆抗体DRm 217是否能阻断Na+-K+-ATP酶/ROS放大器，保护心肌细胞免受ROS损伤。我们发现DRm 217保护心肌细胞免受过氧化氢（H2 O2）诱导的心肌细胞损伤和线粒体功能障碍。DRm 217还可减轻H2 O2对Na+-K+-ATP酶活性、Na+-K+-ATP酶表面表达和Src磷酸化的抑制作用。H_2O_2处理增加了细胞内ROS、线粒体内ROS的含量，并导致细胞内Ca ~（2+）、线粒体内Ca ~（2+）超载。DRm 217关闭Na+-K+-ATPase/ROS放大器，减轻Ca ~（2+）积累，最终抑制ROS和线粒体ROS的产生。这些新的结果有助于我们理解Na+-K+-ATP酶在氧化应激和氧化应激相关疾病中的重要作用。
Reduced Na+-K+-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+-K+-ATPase and ROS form a feed-forward amplifier. The aim of this study was to explore whether DRm217, a proved Na+/K+-ATPase’s DR-region specific monoclonal antibody and direct activator, could disrupt Na+-K+-ATPase/ROS amplifier and protect cardiac cells from ROS-induced injury. We found that DRm217 protected myocardial cells against hydrogen peroxide (H2O2)-induced cardiac cell injury and mitochondrial dysfunction. DRm217 also alleviated the effect of H2O2on inhibition of Na+-K+-ATPase activity, Na+-K+-ATPase cell surface expression, and Src phosphorylation. H2O2-treatment increased intracellular ROS, mitochondrial ROS and induced intracellular Ca2+, mitochondrial Ca2+overload. DRm217 closed Na+-K+-ATPase/ROS amplifier, alleviated Ca2+accumulation and finally inhibited ROS and mitochondrial ROS generation. These novel results may help us to understand the important role of the Na+-K+-ATPase in oxidative stress and oxidative stress-related disease.
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影响因子：
7.4
作者：
Wang Y;Ye Q;Liu C;Xie JX;Yan Y;Lai F;Duan Q;Li X;Tian J;Xie Z
通讯作者：
Xie Z
影响因子：
4.8
作者：
Petrushanko, Irina Yu.;Yakushev, Sergej;Bogdanova, Anna
通讯作者：
Bogdanova, Anna
DOI：
10.2741/1766
发表时间：
2005-09
期刊：
Frontiers in bioscience : a journal and virtual library
影响因子：
--
作者：
Zijian Xie;Joe X. Xie
通讯作者：
Zijian Xie;Joe X. Xie
钙和ROS：相互互动。
影响因子：
11.4
作者：
Görlach A;Bertram K;Hudecova S;Krizanova O
通讯作者：
Krizanova O
影响因子：
3.7
作者：
Li Q;Pogwizd SM;Prabhu SD;Zhou L
通讯作者：
Zhou L