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首页> 外文期刊>Cytokine >Tumor necrosis factor alpha (TNF-alpha) inactivates the PI3-kinase/PKB pathway and induces atrophy and apoptosis in L6 myotubes.
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Tumor necrosis factor alpha (TNF-alpha) inactivates the PI3-kinase/PKB pathway and induces atrophy and apoptosis in L6 myotubes.

机译：肿瘤坏死因子α（TNF-alpha）使PI3激酶/ PKB通路失活，并诱导L6肌管萎缩和凋亡。

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摘要

Muscle atrophy poses a serious concern to patients inflicted with inflammatory diseases. An increasing body of evidence implies that TNF-alpha plays a critical role in muscle atrophy in a number of these clinical settings. The mechanisms mediating its effects are not completely understood and conflicting data regarding its anabolic and catabolic actions exists. To examine the functional significance and detailed morphological characteristics of TNF-alpha-induced muscle proteolysis, differentiated L6 myotubes were subjected to increasing concentrations of recombinant TNF-alpha for 24 and 48 h. Data analysis of cell death showed that TNF-alpha induced a combination of apoptosis and necrosis in high concentrations. TNF-R1, rather than TNF-R2, was significantly upregulated. In addition, the transcription factors, NF-kappaB and FKHR were rapidly activated thus leading to increased expression of ubiquitin ligases, MuRF-1 and MAFbx. Muscle fiber diameter decreased with increasing TNF-alpha concentrations and was associated with attenuation of the PI3-K/Akt pathway as well as significant reductions in differentiation markers. Furthermore, treatment of L6 myotubes with exogenous TNF-alpha strongly potentiates its proteolytic effects through certain MAPKs that are activated. These observations suggest that TNF-alpha induces muscle proteolysis in a dose-dependent manner via various signal transduction pathways.
机译：肌肉萎缩引起患有炎性疾病的患者严重关注。越来越多的证据表明，TNF-α在许多临床情况下在肌肉萎缩中起关键作用。尚未完全了解介导其作用的机制，并且存在有关其同化和分解代谢作用的相互矛盾的数据。为了检查TNF-α诱导的肌肉蛋白水解的功能意义和详细的形态学特征，对分化的L6肌管进行递增浓度的重组TNF-α处理24小时和48小时。细胞死亡的数据分析表明，TNF-α在高浓度时诱导凋亡和坏死的组合。 TNF-R1而不是TNF-R2被显着上调。此外，转录因子NF-κB和FKHR被迅速激活，从而导致泛素连接酶MuRF-1和MAFbx的表达增加。肌肉纤维直径随着TNF-α浓度的增加而减小，并且与PI3-K / Akt通路的衰减以及分化标志物的显着降低有关。此外，用外源性TNF-α处理L6肌管可通过某些被激活的MAPK强烈增强其蛋白水解作用。这些观察结果表明，TNF-α通过各种信号转导途径以剂量依赖的方式诱导肌肉蛋白水解。

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