NADPH oxidase 2 - a novel regulator of molecular responses to exercise

Publikation: Bog/antologi/afhandling/rapportPh.d.-afhandlingForskning

Physical activity plays a protective role in the development of chronic non-communicable diseases. Molecular adaptations explain the beneficial effects of exercise in diverse tissues such as skeletal muscle, adipose tissue, and heart. One of the multiple signals involved in the benefits of exercise are the oxidation-reduction reactions called redox signaling. Reversible and non-reversible posttranslational modifications of cysteine residues are capable of changing the function, localization, or stability of diverse proteins. In skeletal muscle, reactive oxygen species (ROS) are continuously produced and cleared during resting and contracting conditions. There is substantial evidence indicating that redox signaling plays a role in some of the health-benefits elicited by endurance training, however, the precise mechanism has been long unknown.
The aim of the current Ph.D. thesis was therefore to study the involvement of NOX2 and redox signals in the regulation of exercise-stimulated glucose transport and adaptive gene expression in mature skeletal muscle. A combination of harmacological inhibitors and murine NOX2-deficient models were used to address the necessity of NOX2 for glucose transport and adaptive signals induced by acute exercise.
The current Ph.D. thesis demonstrated for the first time that NOX2 is activated during moderateintensity endurance exercise in skeletal muscle and it is a major source of ROS under those conditions. Furthermore, the analyses of genetic mouse models lacking the regulatory NOX2 subunits p47phox and Rac1 revealed striking phenotypic similarities, including severely impaired exercise-stimulated glucose uptake and GLUT4 translocation, indicating that NOX2 is a requirement for this classic acute myocellular adaptation to exercise. Overall, NOX2 is thus a major ROS source regulating adaptive responses to exercise in skeletal muscle.
ForlagDepartment of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen
StatusUdgivet - 2018

ID: 202688825