NOX2 Inhibition Impairs Early Muscle Gene Expression Induced by a Single Exercise Bout.
NOX2 Inhibition Impairs Early Muscle Gene Expression Induced by a Single Exercise Bout.
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DOI：
10.3389/fphys.2016.00282
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发表时间：
2016
影响因子：
4
通讯作者：
Valladares DM
中科院分区：
文献类型：
--
作者：
Henríquez-Olguín C;Díaz-Vegas A;Utreras-Mendoza Y;Campos C;Arias-Calderón M;Llanos P;Contreras-Ferrat A;Espinosa A;Altamirano F;Jaimovich E;Valladares DM
在骨骼肌中，活性氧(ROS)作为信号分子参与运动反应。然而，ROS的来源和参与这些现象的分子机制仍不完全清楚。本工作的目的是研究骨骼肌NADPH氧化酶亚型2(NOX2)在骨骼肌对运动的分子反应中的作用。BALB/c小鼠预先给予NOX2抑制剂apocynin(3 mg/kg)或赋形剂3d后进行游泳运动60min。运动显著上调短指屈肌(FDB)的磷酸化p47Phox水平。此外，近距离连接实验和免疫共沉淀均显示，运动显著增加了NOX2复合体的组装(p47Phox-gp91Phox相互作用)。Apocynin可完全抑制运动诱导的NOX2激活。正如预期的那样，运动增加了FDB肌肉中锰超氧化物歧化酶(MnSOD)、谷胱甘肽过氧化物酶(GPX)、柠檬酸合成酶(CS)、线粒体转录因子A(Tfam)和白细胞介素6(IL-I6)的mRNA水平。此外，apocynin治疗与单次运动后p38 MAP激酶、ERK1/2和NF-κB信号通路的激活减少有关。此外，与运动载体组相比，运动诱导的血浆IL-6增加在apocynin处理组小鼠中减少(p<；0.001)。这些结果在体外运动模型中得到了gp91-dstat的证实。综上所述，apocynin和gp91dstat对NOX2的抑制改变了骨骼肌对运动和电刺激的细胞内信号传递，提示NOX2在急性运动的分子反应中起着关键作用。
Reactive oxygen species (ROS) participate as signaling molecules in response to exercise in skeletal muscle. However, the source of ROS and the molecular mechanisms involved in these phenomena are still not completely understood. The aim of this work was to study the role of skeletal muscle NADPH oxidase isoform 2 (NOX2) in the molecular response to physical exercise in skeletal muscle. BALB/c mice, pre-treated with a NOX2 inhibitor, apocynin, (3 mg/kg) or vehicle for 3 days, were swim-exercised for 60 min. Phospho–p47phox levels were significantly upregulated by exercise in flexor digitorum brevis (FDB). Moreover, exercise significantly increased NOX2 complex assembly (p47phox–gp91phox interaction) demonstrated by both proximity ligation assay and co-immunoprecipitation. Exercise-induced NOX2 activation was completely inhibited by apocynin treatment. As expected, exercise increased the mRNA levels of manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx), citrate synthase (CS), mitochondrial transcription factor A (tfam) and interleukin-6 (IL-I6) in FDB muscles. Moreover, the apocynin treatment was associated to a reduced activation of p38 MAP kinase, ERK 1/2, and NF-κB signaling pathways after a single bout of exercise. Additionally, the increase in plasma IL-6 elicited by exercise was decreased in apocynin-treated mice compared with the exercised vehicle-group (p < 0.001). These results were corroborated using gp91-dstat in an in vitro exercise model. In conclusion, NOX2 inhibition by both apocynin and gp91dstat, alters the intracellular signaling to exercise and electrical stimuli in skeletal muscle, suggesting that NOX2 plays a critical role in molecular response to an acute exercise.