TY  - JOUR
A1  - Hancock, Matthew
A1  - Hafstad, Anne D.
A1  - Nabeebaccus, Adam A.
A1  - Catibog, Norman
A1  - Logan, Angela
A1  - Smyrnias, Ioannis
A1  - Hansen, Synne S.
A1  - Lanner, Johanna
A1  - Schröder, Katrin
A1  - Murphy, Michael P.
A1  - Shah, Ajay M.
A1  - Zhang, Min
T1  - Myocardial NADPH oxidase-4 regulates the physiological response to acute exercise
T2  - eLife
N2  - 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.
KW  - Research article
KW  - human biology and medicine
KW  - exercise
KW  - Nox4
KW  - Nfe2l2
KW  - mitochondria
KW  - reactive oxygen species
KW  - mouse
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/48612
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-486127
SN  - 2050-084X
N1  - Copyright Hancock et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
VL  - 7
IS  - e41044
SP  - 1
EP  - 16
PB  - eLife Sciences Publications
CY  - Cambridge
ER  -