INK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species
INK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species
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DOI：
10.1101/gad.1223004
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发表时间：
2004-12-01
影响因子：
10.5
通讯作者：
Davis, RJ
中科院分区：
文献类型：
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作者：
Ventura, JJ;Cogswell, P;Davis, RJ
C-jun氨基末端激酶(INK)参与了细胞对不同刺激的死亡和存活反应。在这里，我们使用从野生型、MKK4(-/-)MKK7(-/-)和JNK1(-/-)JNK2(-/-)小鼠分离的成纤维细胞，重新研究了墨水在肿瘤坏死因子(TNF)刺激的细胞死亡中的作用。我们证明了墨水可以抑制肿瘤坏死因子刺激的细胞凋亡。然而，我们发现，墨水也可以通过增加活性氧物种(ROS)的产生来加强肿瘤坏死因子刺激的坏死。总之，这些数据表明，墨水可以将肿瘤坏死因子刺激的细胞死亡的平衡从凋亡转移到坏死。坏死增加可能是墨汁介导的应激诱导炎症反应的一个促成因素。
The c-Jun NH2-terminal kinase (INK) has been implicated in both cell death and survival responses to different stimuli. Here we reexamine the function of INK in tumor necrosis factor (TNF)-stimulated cell death using fibroblasts isolated from wild-type, Mkk4(-/-) Mkk7(-/-), and Jnk1(-/-) Jnk2(-/-) mice. We demonstrate that INK can act to suppress TNF-stimulated apoptosis. However, we find that INK can also potentiate TNF-stimulated necrosis by increasing the production of reactive oxygen species (ROS). Together, these data indicate that INK can shift the balance of TNF-stimulated cell death from apoptosis to necrosis. increased necrosis may represent a contributing factor in stress-induced inflammatory responses mediated by INK.