Mitochondria Mediate Tumor Necrosis Factor-α/NF-κB Signaling in Skeletal Muscle Myotubes
Mitochondria Mediate Tumor Necrosis Factor-α/NF-κB Signaling in Skeletal Muscle Myotubes
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DOI：
10.1089/ars.1999.1.1-97
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发表时间：
1999-03-01
影响因子：
6.6
通讯作者：
Reid, Michael B.
中科院分区：
文献类型：
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作者：
Li, Yi-Ping;Atkins, Coleen M.;Reid, Michael B.
肿瘤坏死因子-α（TNF-α）与多种慢性疾病相关的肌肉萎缩和无力有关。最近，我们报道了TNF-α直接诱导分化的骨骼肌肌管中的肌肉蛋白降解，在那里它快速激活核因子κ B（NF-κ B）。我们还发现TNF-α诱导的蛋白质丢失是NF-κ B依赖性的。在本研究中，我们分析了TNF-α激活C2 C12和大鼠原代成肌细胞分化的肌管中NF-κ B的信号通路。我们发现TNF-α激活NF-κ B可被线粒体呼吸链复合物I抑制剂鱼藤酮或amytal阻断。另一方面，复合物III的抑制剂抗霉素A增强了NK-κ B的TNF-α活化。这些结果表明，在介导肌肉中NF-κ B B活化的过程中，源自于肌肉的活性氧（ROS）起着关键作用。此外，我们发现TNF-α刺激蛋白激酶C（PKC）的活性。然而，其他信号转导介质，包括神经酰胺、Ca 2+、磷脂酶A2（PLA（2））和一氧化氮（NO）似乎不参与NF-κ B的激活。抗氧化剂氧化还原信号。1，97-104。
Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappa B (NF-kappa B). W e also have found that protein loss induced by TNF-alpha is NF-kappa B dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappa B in myotubes differentiated from C2C12 and rat primary myoblasts. W e found that activation of NF-kappa B by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappa B. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappa B activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA(2)), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappa B. Antiox. Redox Signal. 1, 97-104.