The STAT3 Inhibitor Stattic Impairs Cardiomyocyte Mitochondrial Function Through Increased Reactive Oxygen Species Formation
The STAT3 Inhibitor Stattic Impairs Cardiomyocyte Mitochondrial Function Through Increased Reactive Oxygen Species Formation
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DOI：
10.2174/138161281939131127115940
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发表时间：
2013-12-01
影响因子：
3.1
通讯作者：
Schulz, Rainer
中科院分区：
文献类型：
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作者：
Boengler, Kerstin;Ungefug, Elvira;Schulz, Rainer
信号转导子和转录激活子3（STAT 3）将应激信号从质膜转导到细胞核，但最近也在线粒体中被鉴定。用STAT 3特异性抑制剂Stattic抑制心肌细胞线粒体STAT 3可降低ADP刺激的呼吸并增强钙诱导的线粒体通透性转换孔（MPTP）开放。本研究的目的是分析Stattic抑制STAT 3的这些作用是否是通过活性氧簇（ROS）的形成介导的。在复合物1底物谷氨酸和苹果酸存在的情况下，连续测量了离体大鼠左心室线粒体的H2 O2形成。使用H2 O2指示剂Amplex UltraRed。Stattic剂量依赖性地增加线粒体ROS形成（Amplex UltraRed荧光斜率/时间; DMSO：0.39 +/- 0.01; 1 μ M Stattic：0.40 +/- 0.03; 10 μ M Stattic：0.71 +/- 0.04; 25 μ M Stattic：1.43 +/- 0.05; 50 μ M Stattic：3.53 +/- 0.23; 100 mu M统计：9.23 +/- 0.69，n= 5份线粒体制备物，p
The signal transducer and activator of transcription 3 (STAT3) transduces stress signals from the plasma membrane to the nucleus but has recently also been identified in mitochondria. Inhibition of cardiomyocyte mitochondrial STAT3 with the STAT3-specific inhibitor Stattic decreases ADP-stimulated respiration and enhances calcium-induced mitochondrial permeability transition pore (MPTP) opening. The aim of the present study was to analyze whether or not these effects of STAT3 inhibition by Stattic are mediated by the formation of reactive oxygen species (ROS).The H2O2 formation from isolated rat left ventricular mitochondria was measured continuously in the presence of the complex 1 substrates glutamate and malate using the H2O2 indicator Amplex UltraRed. Stattic dose-dependently increased mitochondrial ROS formation (slope of Amplex UltraRed fluorescence/ time; DMSO: 0.39 +/- 0.01; 1 mu M Stattic: 0.40 +/- 0.03; 10 mu M Stattic: 0.71 +/- 0.04; 25 mu M Stattic: 1.43 +/- 0.05; 50 mu M Stattic: 3.53 +/- 0.23; 100 mu M Stattic: 9.23 +/- 0.69, n= 5 mitochondrial preparations, p