The mitochondrial Na+/Ca2+exchanger may reduce high glucose-induced oxidative stress and nucleotide-binding oligomerization domain receptor 3 inflammasome activation in endothelial cells
10.11909/j.issn.1671-5411.2015.03.003
- Author:
Yuan ZU
;
Lijuan WAN
;
Shaoyuan CUI
;
Yanping GONG
;
Chunlin LI
- Publication Type:Journal Article
- Keywords:
Calcium ion;
NCLX;
Mitochondria;
NLRP3 inflammasome;
Reactive oxygen species
- From:
Journal of Geriatric Cardiology
2015;(3):270-278
- CountryChina
- Language:Chinese
-
Abstract:
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 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 Ca2+influx and blocked efflux induced by glucose. Un-expectedly, 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 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.
