Skeletal muscle and neutrophil gene responses to exercise

The overall objective of the current proposal is to explore molecular pathways underlying acute stress and recovery responses to a bout of endurance exercise in well trained, male subjects through gene expression profiling via microarray analysis along with verification by RT-PCR of selected genes. It is a major aim to verify the existence of a specific exercise-induced gene pattern and to provide indications for potential novel genes involved in the recovery from and adaptation to exercise. In particular, attention will be drawn on the comparison between circulating polymorphonuclear neutrophils, as a distinct leukocyte subpopulation that is closely related to exercise- induced muscle damage, inflammation and oxidative stress and skeletal muscle tissue for the following reasons: First, to verify the hypothesis whether exercise-induced gene expression changes in circulating immune cells are mirrored in skeletal muscle tissue; second, to explore potential common pathways in the transcriptional regulation in both this particular immune cells and muscle tissue; and third, to particularize molecular interactions between neutrophils and muscle cells. We expect transcriptional changes in both neutrophils and skeletal muscle concerning genes involved in recovery from disruptions to cellular homeostasis, cell viability/apoptosis, cellular protection from oxidative stress and redox-signalling, tissue repair/remodelling and growth/differentiation, and immune/inflammatory responses. Beyond the potential of the findings to contribute to an improved understanding of the molecular responses to exercise (e.g. how exercise mediates its health-promoting effects), the expected results can especially help to clarify whether the changes of certain genes in immune cells can be used as potential surrogate markers for systemic or local (muscular) responses to exercise. Importantly, this may, at least partly, obviate the need of highly-invasive muscle biopsies in exercise studies. Therefore, findings from the proposed study will prove and improve microarrays as a potential tool for monitoring and evaluating both health-related and performance-oriented exerciseraining strategies. Finally, we will also investigate whether expression of certain candidate genes is also reflected on the functional (protein) level. The proposed study will potentially provide novel information, which will link the previous successful FWF-funded research project "Risk Assessment of Participants of an Ironman Triathlon" with the planned follow-up project (with Dr. Neubauer as a previous and current/future co-author and co-coordinator in both projects). The proposal is of utter importance for both the further career development of the applicant as well as for the working group of A/Prof. Karl-Heinz Wagner (Emerging Field Oxidative Stress and DNA Stability, Dep. of Nutritional Sciences, Univ. of Vienna), where Dr. Neubauer holds a key position due to his expertise in the area of sports and exercise sciences. Due to its availability of infrastructure, collaboration and integration of highly experienced researchers from different relevant fields, the Griffith University (AUS) is an ideal research institution for this project.