MCU mediated dysregulation of mitochondrial Ca²⁺ homeostasis is involved in apoptosis of cerebral arterial smooth muscle cells induced by simulated microgravity in rats

  AIM  To investigate the effects of mitochondrial Ca2+ uniporter (MCU) on the apoptosis of cerebral arterial smooth muscle cells induced by simulated microgravity.

  METHODS  Hindlimb unloading tail suspension was performed in rats to simulate the effect of weightlessness on vascular system. The experimental animals were divided into a control group (CON) and a tail suspension group (SUS). After the SUS model was successfully established, apoptosis of cerebral arterial smooth muscle cells was assessed by TUNEL staining and cytochrome cimmunofluorescence staining, and protein expressions of Bcl-2 and Bax and cleaved Caspase-3 and Caspase-9 in cerebral arteries were detected by Western blot. Rhod-2 AM and mitoSOX were used to detect the levels of mitochondrial Ca2+ and reactive oxygen species (ROS), respectively.

  RESULTS  Simulated microgravity enhanced the apoptosis of cerebral artery smooth muscle cells (P < 0.05) and the expression of MCU was down-regulated (P < 0.05). In addition, the mitochondrial Ca2+ decreased (P < 0.05) and ROS levels increased (P < 0.05) in cerebral artery smooth muscle cells isolated from SUS rats.

  CONCLUSION  Down-regulation of MCU expression in cerebral artery of rats leads to the decrease of mitochondrial Ca2+ level and the increase of ROS level, which participate in the apoptosis of cerebral artery smooth muscle cells induced by simulated weightlessness.