Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise
Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise
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DOI：
10.1038/s41467-019-12523-9
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发表时间：
2019-10-11
影响因子：
16.6
通讯作者：
Jensen, Thomas E.
中科院分区：
文献类型：
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作者：
Henriquez-Olguin, Carlos;Knudsen, Jonas R.;Jensen, Thomas E.
活性氧簇(ROS)作为细胞内分隔的第二信使，介导代谢应激适应。在骨骼肌纤维中，ROS被认为在人工诱发的体外收缩过程中刺激依赖于葡萄糖转运蛋白4(GLUT4)的葡萄糖运输，但体内运动是否刺激心肌细胞ROS的产生以控制代谢尚不清楚。在这里，我们将人类和小鼠的运动与荧光染料、基因编码的生物传感器和NADPH氧化酶2(NOX2)功能丧失模型相结合，以证明在中等强度运动中，NOX2是骨骼肌细胞质ROS的主要来源。此外，两个缺乏p47Phox或rac1的NOX2功能丧失小鼠模型在表型上表现出惊人的相似性，包括运动刺激的葡萄糖摄取和GLUT4移位显著减少。这些发现表明，NOX2是一个主要的心肌细胞ROS来源，在中等强度运动中调节葡萄糖的运输能力。
Reactive oxygen species (ROS) act as intracellular compartmentalized second messengers, mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo, but whether myocellular ROS production is stimulated by in vivo exercise to control metabolism is unclear. Here, we combined exercise in humans and mice with fluorescent dyes, genetically-encoded biosensors, and NADPH oxidase 2 (NOX2) loss-of-function models to demonstrate that NOX2 is the main source of cytosolic ROS during moderate-intensity exercise in skeletal muscle. Furthermore, two NOX2 loss-of-function mouse models lacking either p47phox or Rac1 presented striking phenotypic similarities, including greatly reduced exercise-stimulated glucose uptake and GLUT4 translocation. These findings indicate that NOX2 is a major myocellular ROS source, regulating glucose transport capacity during moderate-intensity exercise.