Nuclear factor κB and activating protein 1 are involved in differentiation-related resistance to oxidative stress in skeletal muscle cells
Nuclear factor κB and activating protein 1 are involved in differentiation-related resistance to oxidative stress in skeletal muscle cells
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DOI：
10.1016/j.freeradbiomed.2004.06.021
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发表时间：
2004-10-01
影响因子：
7.4
通讯作者：
Avigliano, L
中科院分区：
文献类型：
--
作者：
Catani, MV;Savini, I;Avigliano, L
骨骼肌细胞持续暴露于氧化应激。因此，它们通过增加适应性反应来补偿环境挑战，其特征在于激活蛋白1（AP-1）和核因子κ B（NF-κ B）介导的内源性酶和非酶抗氧化剂的转录上调。我们研究了串扰的分子参与氧化还原信号在肌肉细胞中，通过使用大鼠L 6C 5和小鼠C2 C12细胞系，这是一个有用的实验模型，用于研究肌肉代谢。我们分析了特定的抗氧化系统，包括谷胱甘肽，硫氧还蛋白还原酶，抗氧化酶，和氧化还原敏感的转录因子AP-1和NF-κ B，在成肌细胞和肌管。我们发现，高水平的NF-κ B DNA结合活性和硫氧还蛋白还原酶，以及抑制AP-1复合物，允许增加的抗氧化酶的表达和C2 C12细胞的生存氧化剂暴露后。相反，L 6C 5成肌细胞具有敏感的表型，与较低水平的硫氧还蛋白还原酶、过氧化氢酶和NF-κ B活性以及较高水平的GSSG和活化AP-1复合物相关。有趣的是，该细胞系获得了抗肿瘤的表型，伴随着氧化剂/抗氧化剂平衡的急剧变化，诱导分化时。总之，这两种细胞系，虽然在生长和分化方面相似，但在氧化还原稳态方面表现出显着的异质性。(C)2004年爱思唯尔公司All rights reserved.
Skeletal muscle cells are continuously exposed to oxidative stress. Thus, they compensate environmental challenges by increasing adaptive responses, characterized by activating protein 1 (AP-1)- and nuclear factor kappaB (NF-kappaB)-mediated transcriptional upregulation of endogenous enzymatic and nonenzymatic antioxidants. We investigated the crosstalk of molecules involved in redox signaling in muscle cells, by using the rat L6C5 and mouse C2C12 cell lines, which represent a useful experimental model for studying muscle metabolism. We analyzed specific antioxidant systems, including glutathione, thioredoxin reductase, and antioxidant enzymes, and the redox-sensitive transcription factors AP-1 and NF-kappaB, in both myoblasts and myotubes. We found that the high levels of NF-kappaB DNA binding activity and thioredoxin reductase, together with inhibitory AP-1 complexes, allowed increased expression of antioxidant enzymes and survival of C2C12 cells after oxidant exposure. On the contrary, L6C5 myoblasts had a sensitive phenotype, correlated with lower levels of thioredoxin reductase, catalase, and NF-kappaB activity and higher levels of GSSG and activating AP-1 complexes. Interestingly, this cell line acquired an apoptosis-resistant phenotype, accompanied by drastic changes in the oxidant/antioxidant balance, when induced to differentiate. In conclusion, the two cell lines, although similar in terms of growth and differentiation, displayed significant heterogeneity in terms of redox homeostasis. (C) 2004 Elsevier Inc. All rights reserved.