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

Area of Science:

• Neuroscience
• Cell Biology
• Pharmacology

Background:

• Brain microvascular endothelial cell (BMEC) dysfunction contributes to neurovascular complications in diabetes mellitus, leading to central nervous system (CNS) disorders.
• Mitoquinone (MitoQ), a mitochondria-targeted antioxidant, demonstrates protective effects in various oxidative stress-related diseases.

Purpose of the Study:

• To investigate the protective effects of MitoQ against high glucose (HG)-induced injury in BMECs.
• To elucidate the underlying molecular mechanisms of MitoQ's action in this context.

Main Methods:

• BMECs were exposed to high glucose (HG) conditions.
• MitoQ treatment was administered to assess its effects on cell viability, mitochondrial function, reactive oxygen species (ROS) production, and apoptosis.
• Expression levels of Nrf2 and HO-1 were analyzed.
• Mitochondrial ROS scavenger (Mito tempol) and Nrf2 inhibitor (ML385) were used to confirm mechanisms.

Main Results:

• HG exposure induced BMEC injury, characterized by reduced Nrf2/HO-1 expression, decreased mitochondrial membrane potential, increased intracellular and mitochondrial ROS, cytoskeletal damage, and apoptosis.
• Mito tempol mitigated HG-induced mitochondrial ROS and protected against cell damage and apoptosis.
• MitoQ treatment upregulated Nrf2/HO-1, improved mitochondrial function, reduced mitochondrial ROS, and attenuated HG-induced cytoskeletal damage and apoptosis.
• Inhibition of Nrf2 abolished the protective effects of MitoQ.

Conclusions:

• MitoQ exerts significant protective effects against high glucose-induced brain microvascular endothelial cell injury.
• The protective mechanism involves the activation of the Nrf2/HO-1 signaling pathway.
• MitoQ's ability to reduce mitochondrial ROS and cellular oxidative stress is crucial for its therapeutic potential in diabetic neurovascular complications.