Diao Jiayu, Wei Jin, Yan Rui, Liu Xin, Li Qing, Lin Lin, Zhu Yanhe, Li Hong
Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
Biochem Biophys Res Commun. 2016 Sep 2;477(4):1024-1030. doi: 10.1016/j.bbrc.2016.07.024. Epub 2016 Jul 8.
Mitochondrial injury characterized by intracellular reactive oxygen species (ROS) accumulation plays a critical role in hyperglycemia-induced myocardium dysfunction. Previous studies have demonstrated that Rosmarinic Acid (RA) treatment and activating Signal transducer and activator of transcription 3 (STAT3) signaling pathway have protective effects on mitochondrial dysfunction in cardiomyocyte, but there is little data regarding cardiomyocyte under condition of high-glucose. The present study was undertaken to determine the relationship between RA and STAT3 activation, as well as their effects on high glucose-induced mitochondrial injury and apoptosis in H9c2 cardiomyocyte. Our results revealed that RA pretreatment suppressed high glucose-induced apoptosis in H9c2 cells. Moreover, the effect of RA on apoptosis was related with improved mitochondrial function, which was demonstrated by that RA attenuated high glucose-induced ROS generation, inhibited mitochondrial permeability transition pore (MPTP) activation, suppressed cytochrome c release and caspase-3 activation. In addition, the phosphorylation of STAT3 in H9c2 cells was inhibited under condition of high-glucose, but RA improved STAT3 phosphorylation. Importantly, inhibition of STAT3 expression by using STAT3-siRNA partly suppressed the effect of RA on high glucose-induced apoptosis. Taken together, pretreatment with RA suppressed high glucose-induced apoptosis in cardiomyocyte by ameliorating mitochondrial function and activating STAT3.
以细胞内活性氧（ROS）积累为特征的线粒体损伤在高血糖诱导的心肌功能障碍中起关键作用。先前的研究表明，迷迭香酸（RA）治疗和激活信号转导子和转录激活子3（STAT3）信号通路对心肌细胞线粒体功能障碍具有保护作用，但关于高糖条件下心肌细胞的数据很少。本研究旨在确定RA与STAT3激活之间的关系，以及它们对高糖诱导的H9c2心肌细胞线粒体损伤和凋亡的影响。我们的结果显示，RA预处理可抑制高糖诱导的H9c2细胞凋亡。此外，RA对凋亡的影响与改善线粒体功能有关，这表现为RA减弱了高糖诱导的ROS生成，抑制了线粒体通透性转换孔（MPTP）的激活，抑制了细胞色素c的释放和caspase-3的激活。此外，在高糖条件下，H9c2细胞中STAT3的磷酸化受到抑制，但RA可改善STAT3的磷酸化。重要的是，使用STAT3-siRNA抑制STAT3表达部分抑制了RA对高糖诱导凋亡的作用。综上所述，RA预处理通过改善线粒体功能和激活STAT3来抑制高糖诱导的心肌细胞凋亡。
