Theophylline treatment improves mitochondrial function after upper cervical spinal cord hemisection.
Theophylline treatment improves mitochondrial function after upper cervical spinal cord hemisection.
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DOI：
10.1016/j.expneurol.2010.01.020
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发表时间：
2010-06
影响因子：
5.3
通讯作者：
Petrov, Theodor
中科院分区：
文献类型：
--
作者：
Huettemann, Maik;Nantwi, Kwaku D.;Lee, Icksoo;Liu, Jenney;Mohiuddin, Syed;Petrov, Theodor
关键词：
线粒体在脊髓损伤中的重要性主要归因于它们参与损伤部位的细胞凋亡。但线粒体功能的另一方面是以 ATP 形式产生 90% 以上的细胞能量，由氧化磷酸化 (OxPhos) 过程介导。细胞色素 c 氧化酶 (CcO) 是 OxPhos 的核心成分，其活性的变化反映了能量需求的变化。最近的一项研究表明，慢性阻塞性肺疾病（COPD）患者的呼吸肌功能因线粒体功能的改变而受到损害。在颈脊髓半切（C2HS）呼吸功能障碍的动物模型中，我们发现茶碱可以改善呼吸功能。在本研究中，我们测试了茶碱通过改善 C2HS 模型中的线粒体功能在细胞水平上改善呼吸功能的假设。我们证明，损伤部位 (C3-C5) 附近的脊髓中 CcO 活性显着增加 (33%)，并且与假手术动物相比，C2HS 后给予茶碱（20 mg/kg，每日 3 次，口服）导致 CcO 活性更显着增加 62%。这些结果与细胞 ATP 水平的显着增加相一致（半切同侧的半膈中 51%）。我们得出的结论是，C2HS 增加了能量需求并激活了线粒体呼吸，茶碱治疗通过激活线粒体 OxPhos 过程来提高能量水平，为 C2HS 模型瘫痪后的组织修复和功能恢复提供能量。
The importance of mitochondria in spinal cord injury has mainly been attributed to their participation in apoptosis at the site of injury. But another aspect of mitochondrial function is the generation of more than 90% of cellular energy in the form of ATP, mediated by the oxidative phosphorylation (OxPhos) process. Cytochrome c oxidase (CcO) is a central OxPhos component and changes in its activity reflect changes in energy demand. A recent study suggests that respiratory muscle function in chronic obstructive pulmonary disease (COPD) patients is compromised via alterations in mitochondrial function. In an animal model of cervical spinal cord hemisection (C2HS) respiratory dysfunction, we have shown that theophylline improves respiratory function. In the present study, we tested the hypothesis that theophylline improves respiratory function at the cellular level via improved mitochondrial function in the C2HS model. We demonstrate that CcO activity was significantly (33%) increased in the spinal cord adjacent to the site of injury (C3–C5), and that administration of theophylline (20 mg/kg 3× daily orally) after C2HS leads to an even more pronounced increase in CcO activity of 62% compared to sham-operated animals. These results are paralleled by a significant increase in cellular ATP levels (51% in the hemidiaphragm ipsilateral to the hemisection). We conclude that C2HS increases energy demand and activates mitochondrial respiration, and that theophylline treatment improves energy levels through activation of the mitochondrial OxPhos process to provide energy for tissue repair and functional recovery after paralysis in the C2HS model.
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影响因子：
4.8
作者：
Samavati, Lobelia;Lee, Icksoo;Huttemann, Maik
通讯作者：
Huttemann, Maik
影响因子：
4.1
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ITO, T;ALLEN, N;YASHON, D
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影响因子：
3.3
作者：
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通讯作者：
Bolser, DC
影响因子：
5.3
作者：
Fuller, D. D.;Doperalski, N. J.;Reier, P. J.
通讯作者：
Reier, P. J.