L-2-Oxothiazolidine-4-carboxylate reverses glutathione oxidation and delays fatigue of skeletal muscle in vitro
L-2-Oxothiazolidine-4-carboxylate reverses glutathione oxidation and delays fatigue of skeletal muscle in vitro
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DOI：
10.1152/japplphysiol.00001.2009
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发表时间：
2009-07-01
影响因子：
3.3
通讯作者：
Reid, Michael B.
中科院分区：
文献类型：
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作者：
Ferreira, Leonardo F.;Gilliam, Laura A. A.;Reid, Michael B.
Ferreira LF, Gilliam LA, Reid MB. l -2-氧噻唑烷-4-羧酸盐在体外逆转谷胱甘肽氧化和延缓骨骼肌疲劳。中国生物医学工程学报（英文版），2009。首次发表于2009年4月30日；doi: 10.1152 / japplphysiol.00001.2009。-疲劳运动促进细胞内硫醇氧化，尤其是谷胱甘肽。反对或逆转硫醇氧化的干预措施可以抑制疲劳。还原半胱氨酸供体l -2-氧噻唑烷-4-羧酸盐（OTC）支持谷胱甘肽合成，并被批准用于人类，但尚未评估其对骨骼肌的影响。我们检验了OTC会增加还原性谷胱甘肽（GSH）水平和降低氧化性谷胱甘肽水平的假设，以及2)抑制疲劳的功能指标。将成年雄性ICR小鼠膈纤维束与缓冲液（对照，C）或OTC （10 mM）在37℃下孵育1或2小时。以n -乙酰半胱氨酸（NAC, 10 mM）为阳性对照。我们测量了谷胱甘肽代谢物和疲劳特征。我们发现肌肉GSH含量在OTC或NAC孵育1小时后增加，但在孵育2小时后没有改变。OTC或NAC治疗1小时可减缓重复刺激下的肌力下降[300 s时的平均（SD）疲劳指数：OTC = 34 +/- 6% vs. C = 50 +/- 8%, P < 0.05；NAC = 55 +/- 4% vs. C = 65 +/- 8%, P < 0.05] 2 h OTC治疗组（OTC = 38 +/- 9% vs. C = 51 +/- 9%, P < 0.05）也是如此。这些结果表明，在目前的实验条件下，OTC可以调节肌肉GSH池，抗疲劳。
Ferreira LF, Gilliam LA, Reid MB. L-2-Oxothiazolidine-4-carboxylate reverses glutathione oxidation and delays fatigue of skeletal muscle in vitro. J Appl Physiol 107: 211-216, 2009. First published April 30, 2009; doi:10.1152/japplphysiol.00001.2009.-Fatiguing exercise promotes oxidation of intracellular thiols, notably glutathione. Interventions that oppose or reverse thiol oxidation can inhibit fatigue. The reduced cysteine donor L-2-oxothiazolidine-4-carboxylate (OTC) supports glutathione synthesis and is approved for use in humans but has not been evaluated for effects on skeletal muscle. We tested the hypotheses that OTC would 1) increase reduced glutathione (GSH) levels and decrease oxidized glutathione, and 2) inhibit functional indexes of fatigue. Diaphragm fiber bundles from adult male ICR mice were incubated for 1 or 2 h at 37 degrees C with buffer (control, C) or OTC (10 mM). N-acetylcysteine (NAC; 10 mM) was used as a positive control. We measured GSH metabolites and fatigue characteristics. We found that muscle GSH content was increased after 1-h incubation with OTC or NAC but was not altered after 2-h incubation. One-hour treatment with OTC or NAC slowed the decline in force with repetitive stimulation [mean (SD) fatigue index at 300 s: OTC = 34 +/- 6% vs. C = 50 +/- 8%, P < 0.05; NAC = 55 +/- 4% vs. C = 65 +/- 8%, P < 0.05] as did the 2-h OTC treatment (OTC = 38 +/- 9% vs. C = 51 +/- 9%, P < 0.05). These results demonstrate that OTC modulates the muscle GSH pool and opposes fatigue under the current experimental conditions.