Hancock 2018 Elife
|Hancock M, Hafstad AD, Nabeebaccus AA, Catibog N, Logan A, Smyrnias I, Hansen SS, Lanner J, Schröder K, Murphy MP, Shah AM, Zhang M (2018) Myocardial NADPH oxidase-4 regulates the physiological response to acute exercise. Elife 7:e41044.|
Abstract: Regular exercise has widespread health benefits. Fundamental to these beneficial effects is the ability of the heart to intermittently and substantially increase its performance without incurring damage, but the underlying homeostatic mechanisms are unclear. We identify the ROS-generating NADPH oxidase-4 (Nox4) as an essential regulator of exercise performance in mice. Myocardial Nox4 levels increase during acute exercise and trigger activation of the transcription factor Nrf2, with the induction of multiple endogenous antioxidants. Cardiomyocyte-specific Nox4-deficient (csNox4KO) mice display a loss of exercise-induced Nrf2 activation, cardiac oxidative stress and reduced exercise performance. Cardiomyocyte-specific Nrf2-deficient (csNrf2KO) mice exhibit similar compromised exercise capacity, with mitochondrial and cardiac dysfunction. Supplementation with an Nrf2 activator or a mitochondria-targeted antioxidant effectively restores cardiac performance and exercise capacity in csNox4KO and csNrf2KO mice respectively. The Nox4/Nrf2 axis therefore drives a hormetic response that is required for optimal cardiac mitochondrial and contractile function during physiological exercise.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Stress:Oxidative stress;RONS Organism: Mouse Tissue;cell: Heart Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, S, NS, ROX HRR: Oxygraph-2k