Aerobic fitness levels are one of the strongest predictors of morbidity and mortality in healthy and chronic diseases population. These benefits are mediated in part by extensive metabolic and molecular remodeling of skeletal muscle. However, the mechanisms underlying this significant association are still unresolved. In the present project, we propose to further explore this association by studying the relative role of the Heme Oxygenase-1 (HO-1) and Hemopexin (HPx), which play important roles in cytoprotection. The cytoprotective effects of HO-1 and HPx rely on their ability to bind and catabolize heme and preventing heme-induced oxidative stress and programmed cell death. The contribution of HO-1 and HPx for aerobic exercise training inducing cytoprotection remains to be determined. Therefore, presently we will investigate the functional and molecular contribution of HO-1 and HPx detoxifying heme effects for accrued aerobic fitness by exercise training and its relationship with muscle cell protection, and improved oxidative metabolism. Our central hypothesis is that the increased aerobic fitness by exercise training will be linked to a better heme clearance by HO-1 and HPx. To test this hypothesis, we will perform in vivo experiments using skeletal muscle-specific HO-1-KO mice and HPx null mice submitted to aerobic exercise training. Additionally, we will investigate the contribution of heme catabolism products including bilirubin and carbon monoxide in these mice and their control groups. To further understand the relative cytoprotective role of HO-1 and HPx in muscle cells, we will perform loss and gain of function experiments in primary cultured myotubes. Thus, we propose that HO-1 and HPx may emerge as potential targets to modulate the link between aerobic fitness and health.
News published in Agência FAPESP Newsletter about the scholarship: