Significance of NOX2 for muscle function
Reactive oxygen species (ROS) in skeletal muscle are both suggested to be beneficial signal molecules that stimulate adaptation in the working muscles during and after exercise but are also harmful in excessive amounts where they can result in pre-diabetic insulin resistance and loss of muscle mass.
ROS formation is often described as a harmful byproduct of respiration in the cells' power plants, mitochondria. However, there are other sources of oxygen radicals in skeletal muscle, including the superoxide radical-forming enzyme NOX2. NOX2 has been shown in previous mouse studies to be a major source of oxygen radicals both during muscle contraction in isolated muscle and in various diseased conditions such as insulin resistance and muscle dystrophy.
In this project we have removed 2 regulators of NOX2 in mouse skeletal muscle. By comparison with normal mice and in combination with a new oxygen radical preservation technique and transfection with genetically encoded ROS-targeted biosensors, this enables us to tease out the importance of NOX2 for the adaptability of the muscle to various conditions, including physical activity, obesity-associated insulin resistance and various forms for muscle atrophy.
It is expected that the project will enable a detailed mapping of the role of NOX2 in ROS formation and function in skeletal muscle under various conditions. As NOX2 is expressed in many cell types in the body and a possible candidate for drug intervention, this knowledge is likely to be widely used.
Novo Nordisk Foundation.