ERK and JNK mediate TNFα-induced p53 activation in apoptotic and autophagic L929 cell death
ERK and JNK mediate TNFα-induced p53 activation in apoptotic and autophagic L929 cell death
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DOI：
10.1016/j.bbrc.2008.09.018
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发表时间：
2008-11-21
影响因子：
3.1
通讯作者：
Ikejima, Takashi
中科院分区：
文献类型：
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作者：
Cheng, Yan;Qiu, Feng;Ikejima, Takashi
本研究旨在探讨肿瘤坏死因子α诱导L929细胞凋亡和自噬的分子机制。在此，我们发现，用肿瘤坏死因子α处理L929细胞后，P53活性呈时间依赖性增加。抑制P53活化可减少肿瘤坏死因子α诱导的细胞凋亡和自噬，并伴随A1F、Beclin1和Lc3水平的降低。随后，肿瘤坏死因子α在细胞凋亡和自噬中激活ERK、JNK和p38，其中ERK/JNK起促进作用，而p38起抑制作用。此外，ERK或ERK可降低肿瘤坏死因子α诱导的P53激活，但不受p38抑制的影响。进一步数据显示，抑制JNK抑制、自噬减少了肿瘤坏死因子α诱导的L929细胞的凋亡。综上所述，这些结果表明，TnFa诱导的MAPKs在凋亡和自噬细胞死亡中介导了P53的激活，而自噬可能在与死亡信号通路相关的情况下放大了细胞的凋亡。(C)2008 Elsevier Inc.保留所有权利。
The object of this study was to investigate the molecular mechanisms mediating TNF alpha-induced apoptosis and autophagy in L929 cells. Herein, we found that the treatment of L929 cells with TNF alpha caused a time-dependent increase in p53 activity. The inhibition of p53 activation reduced TNF alpha-induced apoptosis and autophagy that were accompanied by the decrease in the levels of A1F, Beclin1 and LC3. Subsequently, TNF alpha activated ERK, JNK and p38 in apoptosis and autopahgy, in which ERK/JNK played a promoting role whereas p38 played an inhibiting one. In addition, TNF alpha-induced p53 activation was reduced by ERK or but it was not affected by p38 inhibition. Further data showed that the inhibition of JNK inhibition, autophagy reduced TNF alpha-induced apoptosis in L929 cells. In conclusion, these results demonstrate that TNFa-induced MAPKs mediate p53 activation in apoptotic and autophagic cell death, as well as autophagy may amplify apoptosis when associated with a death signaling pathway. (c) 2008 Elsevier Inc. All rights reserved.