title: 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.
abstract: BACKGROUND
  The mitochondrial Na(+)/Ca(2+) exchanger, NCLX, plays an important role in the balance between Ca(2+) influx and efflux across the mitochondrial inner membrane in endothelial cells. 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 production but are also important sites of reactive oxygen species (ROS) generation and nucleotide-binding oligomerization domain receptor 3 (NLRP3) inflammasome activation.
  
  
  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 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.
authors.affiliation: Department of Geriatric Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zu
authors.affiliation: Department of Geriatric Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Wan
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital, Beijing, China.
authors.forename: Shao-Yuan
authors.initials: SY
authors.lastname: Cui
authors.affiliation: Department of Geriatric Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Gong
authors.affiliation: Department of Geriatric Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Li
keywords: Calcium ion; Mitochondria; NCLX; NLRP3 inflammasome; Reactive oxygen species