MitoQ protects against high glucose-induced brain microvascular endothelial cells injury via the Nrf2/HO-1 pathway

• Main Authors: Min-yan Yang (Author), Zhen Fan (Author), Zhao Zhang (Author), Jin Fan (Author)
• Format: Book
• Published: Elsevier, 2021-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1347-8613; 10.1016/j.jphs.2020.10.007
• Keywords: MitoQ; Nrf2; Mitochondrial ROS; Brain microvascular endothelial cells; Diabetes; Therapeutics. Pharmacology; RM1-950
• Source: Journal of Pharmacological Sciences, Vol 145, Iss 1, Pp 105-114 (2021)

Brain microvascular endothelial cells (BMECs) dysfunction is related to the pathogenesis of neurovascular complication of diabetes mellitus that adversely lead to various CNS disorders. Mitoquinone (MitoQ) is a mitochondria targeted antioxidant that exerts multiple protective effects in many oxidative damage-related diseases. In this study, we determined the protective effects of MitoQ on high glucose (HG)-induced BMECs injury and investigated the underlying mechanism. We found that HG significantly reduced the expression of Nrf2 and HO-1, decreased mitochondrial membrane potential, increased intracellular and mitochondrial reactive oxygen species (ROS) generation, induced cytoskeletal damage and apoptosis in BMECs. In addition, Mito tempol, a mitochondrial ROS scavenger, significantly reduced HG-induced mitochondrial ROS production and attenuated cytoskeletal damage and cell apoptosis, suggesting MtROS production was involved in HG-induced BMECs injury. Moreover, we found that MitoQ treatment significantly upregulated the expression of Nrf2 and HO-1 in HG-induced BMECs, which is accompanied by improved mitochondrial membrane potential and decreased MtROS production. Meanwhile, MitoQ treatment also remarkably attenuated HG-induced cytoskeletal damage and cell apoptosis in BMECs. However, inhibitor of Nrf2 with ML385 impaired the protective effects of MitoQ in HG-induced BMECs. In conclusion, our results suggest that MitoQ exerts protective effect on HG-induced BMECs injury via activating Nrf2/HO-1 pathway.