The mitochondrial Na(+)/Ca(2+) exchanger may reduce high glucose-induced oxidative stress and nucleotide-binding oligomerization domain receptor 3 inflammasome activation in endothelial cells.
The mitochondrial Na(+)/Ca(2+) exchanger may reduce high glucose-induced oxidative stress and nucleotide-binding oligomerization domain receptor 3 inflammasome activation in endothelial cells.
复制标题
线粒体 Na /Ca2 交换器可能会减少高葡萄糖诱导的氧化应激和内皮细胞中核苷酸结合寡聚化结构域受体 3 炎症小体的激活
DOI：
10.11909/j.issn.1671-5411.2015.03.003
复制
发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Li CL
中科院分区：
文献类型：
--
作者：
Zu Y;Wan LJ;Cui SY;Gong YP;Li CL
线粒体Na+/Ca2+交换器NCLX在内皮细胞线粒体内膜Ca2+内流和外排平衡中起重要作用。线粒体代谢可能受到NCLX活性的影响，因为Ca2+激活了克雷布斯循环的几种酶。目前认为，线粒体不仅是能量产生的中心，也是活性氧（ROS）生成和核苷酸结合寡聚结构域受体3 （NLRP3）炎性体激活的重要位点。方法与结果研究葡萄糖诱导的NCLX在大鼠主动脉内皮细胞（RAECs）中的功能。首先，我们检测到注射链脲佐菌素诱导的糖尿病大鼠内皮中NCLX表达增加。接下来，使用共聚焦分析检测NCLX表达和线粒体的共定位。使用siRNA构建体（sinclair）抑制NCLX的表达，可增强线粒体Ca2+内流并阻断葡萄糖诱导的外排。出乎意料的是，沉默NCLX表达可诱导ROS生成增加和NLRP3炎性体活化。这些发现表明，NCLX影响葡萄糖依赖的线粒体Ca2+信号，从而调节高糖条件下ROS的产生和NLRP3炎性体的激活。在高糖刺激的早期阶段，内皮细胞中NCLX表达增加以补偿线粒体的维持、稳定和功能。
Background The mitochondrial Na+/Ca2+ exchanger, NCLX, plays an important role in the balance between Ca2+ influx and efflux across the mitochondrial inner membrane in endothelial cells. Mitochondrial metabolism is likely to be affected by the activity of NCLX because Ca2+ activates several enzymes of the Krebs cycle. It is currently believed that mitochondria are not only centers of energy production but are also important sites of reactive oxygen species (ROS) generation and nucleotide-binding oligomerization domain receptor 3 (NLRP3) inflammasome activation. Methods & Results This study focused on NCLX function, in rat aortic endothelial cells (RAECs), induced by glucose. First, we detected an increase in NCLX expression in the endothelia of rats with diabetes mellitus, which was induced by an injection of streptozotocin. Next, colocalization of NCLX expression and mitochondria was detected using confocal analysis. Suppression of NCLX expression, using an siRNA construct (siNCLX), enhanced mitochondrial Ca2+ influx and blocked efflux induced by glucose. Unexpectedly, silencing of NCLX expression induced increased ROS generation and NLRP3 inflammasome activation. Conclusions These findings suggest that NCLX affects glucose-dependent mitochondrial Ca2+ signaling, thereby regulating ROS generation and NLRP3 inflammasome activation in high glucose conditions. In the early stages of high glucose stimulation, NCLX expression increases to compensate in order to self-protect mitochondrial maintenance, stability, and function in endothelial cells.
登录
查看更多内容
影响因子：
4.3
作者：
Csordas, Gyoergy;Hajnoczky, Gyoergy
通讯作者：
Hajnoczky, Gyoergy
影响因子：
32.4
作者：
Iyer SS;He Q;Janczy JR;Elliott EI;Zhong Z;Olivier AK;Sadler JJ;Knepper-Adrian V;Han R;Qiao L;Eisenbarth SC;Nauseef WM;Cassel SL;Sutterwala FS
通讯作者：
Sutterwala FS
影响因子：
4
作者：
Kim, Kwang-Youn;Cho, Hyo-Jin;Ahn, Soon-Cheol
通讯作者：
Ahn, Soon-Cheol
影响因子：
4.8
作者：
Cai, XJ;Lytton, J
通讯作者：
Lytton, J
影响因子：
64.8
作者：
Baughman, Joshua M.;Perocchi, Fabiana;Girgis, Hany S.;Plovanich, Molly;Belcher-Timme, Casey A.;Sancak, Yasemin;Bao, X. Robert;Strittmatter, Laura;Goldberger, Olga;Bogorad, Roman L.;Koteliansky, Victor;Mootha, Vamsi K.
通讯作者：
Mootha, Vamsi K.