Targeting Dynamin 2 as a Novel Pathway to Inhibit Cardiomyocyte Apoptosis Following Oxidative Stress

Area of Science:

• Cardiovascular Biology
• Mitochondrial Dynamics
• Cellular Stress Response

Background:

• Drp-1 inhibition mitigates ischemia/reperfusion injury in cardiomyocytes by limiting ROS and apoptosis.
• The role of Dynamin 2 in cardiomyocyte oxidative stress remains largely unexplored.

Purpose of the Study:

• To investigate the protective effects of Dynamin 2 inhibition against oxidative stress-induced apoptosis and ROS production in cardiomyocytes.
• To compare the effects of Dynamin 2 inhibition with Drp1 inhibition.

Main Methods:

• Neonatal mouse cardiomyocytes were subjected to oxidative stress.
• Dynamin 2 was inhibited using lentiviral shRNA (lv5-shRNA).
• Cells were treated with Drp1 inhibitor (mdivi-1) or Dynamin 2/Drp1 inhibitor (Dynasore). Apoptosis, mitochondrial morphology, transmembrane potential (ΔΨm), and ROS production were assessed.

Main Results:

• Inhibition of both Drp1 and Dynamin 2 attenuated mitochondrial fragmentation, preserved ΔΨm, reduced ROS, and decreased apoptosis.
• Dynamin 2 knockdown alone alleviated mitochondrial fragmentation and reduced ROS production and apoptosis.
• Combined inhibition with Dynasore enhanced the protective effects of Dynamin 2 knockdown.

Conclusions:

• Dynamin 2 inhibition, similar to Drp1 inhibition, attenuates oxidative stress-induced apoptosis and ROS production in cardiomyocytes.
• Dynamin 2 plays a significant role as a mediator of oxidative stress in the heart.