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

BackgroundThe mitochondrial Na +/Ca2+ exchanger， NCLX，越过 mitochondrial 处于在 Ca 2+ 流入和流出之间的平衡起一个重要作用在 endothelial 房间的内部膜。因为 Ca 2+ 激活克雷布斯周期的几酶， Mitochondrial 新陈代谢是可能的被 NCLX 的活动影响。线粒体是精力生产的中心，但是也是反应的氧的重要地点，这当前被相信不仅种类(ROS ) 产生和核苷酸绑定 oligomerization 领域受体 3 (NLRP3 ) inflammasome activation.Methods &；ResultsThis 学习集中了于 NCLX 功能，在老鼠大动脉的 endothelial 房间(RAEC ) ，由葡萄糖导致了。首先，我们与糖尿病 mellitus 在老鼠的 endothelia 在 NCLX 表示检测了增加，它被 streptozotocin 的注射导致。下次， NCLX 表示和线粒体的 colocalization 用共焦的分析被检测。用 siRNA 构造(siNCLX ) ， NCLX 表示的抑制提高了 2+ 流入和堵住的流出由葡萄糖导致了的 mitochondrial Ca。出人意料地，导致的 NCLX 表示的 silencing 增加了 ROS 产生和 NLRP3 inflammasome activation.ConclusionsThese 调查结果建议 NCLX 影响葡萄糖依赖者 mitochondrial Ca 2+ 发信号，从而在高葡萄糖调整 ROS 产生和 NLRP3 inflammasome 激活调节。在高葡萄糖刺激的早阶段， NCLX 表示增加补偿以便在 endothelial 房间的自我保护的 mitochondrial 维护，稳定性，和功能。

Background The mitochondrial Na^＋/Ca^2＋ exchanger, NCLX, plays an important role in the balance between Ca2. influx and efflux across the mitochondrial inner membrane in endothelial ceils. Mitochondrial metabolism is likely to be affected by the activity of NCLX because Ca^2＋ activates several enzymes of the Krebs cycle. It is currently believed that mitochondria are not only centers of energy produc- tion 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 Ca^2＋ 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 Ca^2＋ signaling, thereby regulating ROS generation and NLRP3 in- flammasome 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.