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.
Pubmed ID: 30589411 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis monoclonal targets CDH5
View all literature mentionsThis polyclonal targets Mouse p47-phox
View all literature mentionsThis polyclonal targets TXNRD3, TXNRD2
View all literature mentionsThis polyclonal targets Superoxide Dismutase 2
View all literature mentionsThis polyclonal targets Human Catalase
View all literature mentionsThis polyclonal targets 4 Hydroxynonenal antibody
View all literature mentionsThis polyclonal targets Nrf2 (H-300)
View all literature mentionsThis polyclonal targets PRDX3
View all literature mentionsThis polyclonal targets GSTA2 antibody produced in rabbit
View all literature mentionsThis monoclonal targets GAPDH antibody produced in mouse
View all literature mentionsMus musculus with name B6.129S4(Cg)-Myl2tm1(cre)Krc/AchakJ from IMSR.
View all literature mentions