| Summary: | Exercise is associated with a plethora of transcriptional responses preceding metabolic and cardiovascular adaptations, often attributed to ROS. The relationship between ROS and the metabolic and genomic response to exercise has not been fully defined. This thesis explored ROS generation following moderate aerobic exercise in combination with either antioxidant (lycopene) supplementation (to limit ROS formation) or hypoxia (to induce a reductive, rather than oxidative stress) in healthy males. Measures of ROS production and oxidative stress (EPR spectroscopy, LOOH, isoprostanes, SOD, LSA) and metabolism (lactate, RER) were used to quantify states of cellular stress in plasma and serum samples. These indices were considered in conjunction with microarray analysis to measure gene expression, Paxgene technique, using whole blood, post exercise. In addition, metabolomic analysis (untargeted mass spectrometry) was used to quantify differences in plasma metabolites post exercise. The results discussed within the thesis suggest that acute exercise provides stimuli for adaptations often mediated by exercise training. Lycopene supplementation may increase antioxidant capacity yet this had no measurable effect on antioxidant function, oxidative stress or gene regulation. While hypoxia appeared to increase oxidative stress this was somewhat ameliorated by exercise. Furthermore, several transcriptional responses to exercise in hypoxia were different from those in normoxia: hypoxic exercise resulted in the selective upregulation of mitochondrial transport proteins, glycolytic enzymes combined with the down regulation of AMPK suggesting an increased capacity for glycolytic metabolism and ability to withstand metabolic but not oxidative stress. Exercise caused the upregulation of genes associated with mitochondrial biogenesis, many of which were unchanged or down regulated in hypoxia. Hypoxia also appeared to reduce genome stability via the down regulation of WRN and CHAF-l. However, these changes may not be reliant upon alterations in ROS but other factors, both within and between individuals, such as insulin sensitivity, aerobic fitness or metabolic capacity.
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