Exercise-induced Nrf2 activation increases antioxidant defenses in skeletal muscles

Following the discovery that exercise increases the production of reactive oxygen species in contracting skeletal muscles, evidence quickly emerged that endurance exercise training increases the abundance of key antioxidant enzymes in the trained muscles. Since these early observations, knowledge about the impact that regular exercise has on skeletal muscle antioxidant capacity has increased significantly. Importantly, in recent years, our understanding of the cell signaling pathways responsible for this exercise-induced increase in antioxidant enzymes has expanded exponentially. Therefore, the goals of this review are: 1) summarize our knowledge about the influence that exercise training has on the abundance of key antioxidant enzymes in skeletal muscles; and 2) to provide a state-of-the-art review of the nuclear factor erythroid 2-related factor (Nrf2) signaling pathway that is responsible for many of the exercise-induced changes in muscle antioxidant capacity. We begin with a discussion of the sources of reactive oxygen species in contracting muscles and then examine the exercise-induced changes in the antioxidant enzymes that eliminate both superoxide radicals and hydrogen peroxide in muscle fibers. We conclude with a discussion of the advances in our understanding of the exercise-induced control of the Nrf2 signaling pathway that is responsible for the expression of numerous antioxidant proteins. In hopes of stimulating future research, we also identify gaps in our knowledge about the signaling pathways responsible for the exercise-induced increases in muscle antioxidant enzymes.