Increased SOD2 in the diaphragm contributes to exercise-induced protection against ventilator-induced diaphragm dysfunction.
Increased SOD2 in the diaphragm contributes to exercise-induced protection against ventilator-induced diaphragm dysfunction.
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DOI：
10.1016/j.redox.2018.10.005
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发表时间：
2019-01
期刊：
影响因子：
11.4
通讯作者：
Powers SK
中科院分区：
文献类型：
--
作者：
Morton AB;Smuder AJ;Wiggs MP;Hall SE;Ahn B;Hinkley JM;Ichinoseki-Sekine N;Huertas AM;Ozdemir M;Yoshihara T;Wawrzyniak NR;Powers SK
机械通气（MV）是许多危重患者的救命手段。不幸的是，长时间的MV导致膈肌快速萎缩和收缩功能障碍，统称为呼吸机诱发的膈肌功能障碍（VIDD）。最近的证据表明，在MV之前进行的耐力运动训练可以保护隔膜免受视频干扰。虽然这种运动诱导的抗VIDD保护机制尚不清楚，但可能需要增加隔膜抗氧化剂的表达。为了研究增加抗氧化剂在这种保护中的作用，我们测试了线粒体抗氧化酶超氧化物歧化酶2 （SOD2）水平升高是实现运动诱导的抗VIDD保护所必需的假设。从两方面考察了因果关系。首先，我们通过在运动后递送一种针对SOD2的反义寡核苷酸来阻止运动引起的膈肌SOD2的增加。其次，通过转基因过表达SOD2，我们确定了独立于运动训练的SOD2增加对横膈膜的影响。这些实验结果表明，预防运动诱导的膈肌SOD2增加导致运动介导的对mv诱导的膈肌萎缩的保护作用丧失，并部分丧失对mv诱导的膈肌收缩功能障碍的保护作用。相反，在独立于运动的情况下，转基因SOD2在横膈膜中的过表达并不能保护mv诱导的膈肌萎缩，只能部分保护mv诱导的膈肌收缩功能障碍。总的来说，这些结果表明，增加膈肌SOD2水平对于实现运动诱导的抗VIDD保护的全部益处是必不可少的。长时间机械通气导致膈肌无力，这被称为呼吸机诱发膈功能障碍（VIDD）。在机械通气之前进行的耐力运动训练可以保护隔膜免受VIDD的侵害。防止运动引起的隔膜超氧化物歧化酶2 （SOD2）的增加部分地消除了运动对VIDD的保护。在隔膜中转基因过表达SOD2只提供部分抗VIDD保护。我们得出结论，横膈膜中SOD2丰度的增加有助于运动诱导的对VIDD的保护。
Mechanical ventilation (MV) is a life-saving intervention for many critically ill patients. Unfortunately, prolonged MV results in rapid diaphragmatic atrophy and contractile dysfunction, collectively termed ventilator-induced diaphragm dysfunction (VIDD). Recent evidence reveals that endurance exercise training, performed prior to MV, protects the diaphragm against VIDD. While the mechanism(s) responsible for this exercise-induced protection against VIDD remain unknown, increased diaphragm antioxidant expression may be required. To investigate the role that increased antioxidants play in this protection, we tested the hypothesis that elevated levels of the mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2) is required to achieve exercise-induced protection against VIDD. Cause and effect was investigated in two ways. First, we prevented the exercise-induced increase in diaphragmatic SOD2 via delivery of an antisense oligonucleotide targeted against SOD2 post-exercise. Second, using transgene overexpression of SOD2, we determined the effects of increased SOD2 in the diaphragm independent of exercise training. Results from these experiments revealed that prevention of the exercise-induced increases in diaphragmatic SOD2 results in a loss of exercise-mediated protection against MV-induced diaphragm atrophy and a partial loss of protection against MV-induced diaphragmatic contractile dysfunction. In contrast, transgenic overexpression of SOD2 in the diaphragm, independent of exercise, did not protect against MV-induced diaphragmatic atrophy and provided only partial protection against MV-induced diaphragmatic contractile dysfunction. Collectively, these results demonstrate that increased diaphragmatic levels of SOD2 are essential to achieve the full benefit of exercise-induced protection against VIDD. Prolonged mechanical ventilation results in diaphragmatic weakness which is labeled as ventilator-induced diaphragm dysfunction (VIDD). Endurance exercise training performed prior to mechanical ventilation protects the diaphragm against VIDD. Preventing exercise-induced increases of superoxide dismutase 2 (SOD2) in the diaphragm partially abolishes exercise protection against VIDD. Transgenic overexpression of SOD2 in the diaphragm provides only partial protection against VIDD. We conclude that increases in SOD2 abundance in the diaphragm contributes to the exercise-induced protection against VIDD.
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影响因子：
3.3
作者：
Falk, D. J.;DeRuisseau, K. C.;Powers, S. K.
通讯作者：
Powers, S. K.
影响因子：
3.3
作者：
Kwon, Oh Sung;Smuder, Ashley J.;Powers, Scott K.
通讯作者：
Powers, Scott K.
影响因子：
8.8
作者：
Bruells, Christian S.;Smuder, Ashley J.;Powers, Scott K.
通讯作者：
Powers, Scott K.
DOI：
10.1097/00005768-199712000-00005
发表时间：
1997-12-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Powers, SK;Demirel, HA;Prezant, D
通讯作者：
Prezant, D
影响因子：
8.8
作者：
Nelson WB;Smuder AJ;Hudson MB;Talbert EE;Powers SK
通讯作者：
Powers SK