Constitutive activation of AKT pathway inhibits TNF-induced apoptosis in mitochondrial DNA-deficient human myelogenous leukemia ML-1a.
Constitutive activation of AKT pathway inhibits TNF-induced apoptosis in mitochondrial DNA-deficient human myelogenous leukemia ML-1a.
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DOI：
10.1016/j.canlet.2008.03.020
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发表时间：
2008-09
期刊：
影响因子：
9.7
通讯作者：
Seigo Suzuki;A. Naito;Takayuki Asano;T. Evans;S. Reddy;M. Higuchi
中科院分区：
文献类型：
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作者：
Seigo Suzuki;A. Naito;Takayuki Asano;T. Evans;S. Reddy;M. Higuchi
TNF加蛋白质合成抑制剂环己酰亚胺诱导人髓性白血病ML-1a细胞凋亡，但不诱导C19细胞凋亡，C19细胞来源于ML-1a，呼吸缺失线粒体DNA缺陷。为了研究线粒体DNA耗竭如何抑制细胞凋亡，我们研究了AKT。AKT及其磷酸化形式仅在C19中观察到，表明mtDNA的缺失增加了蛋白质和AKT的活性形式。用抑制PI-3激酶和抑制AKT的LY 294002处理C19，显著增加TNF加放线菌酮的凋亡诱导，并消除AKT的磷酸化。这些结果表明，AKT激活诱导的线粒体DNA的消耗和抑制TNF诱导的细胞凋亡。
TNF plus protein synthesis inhibitor cycloheximide-induced apoptosis in human myelogenous leukemia ML-1a but not in C19, respiration minus mitochondrial DNA-deficient C19 cells, derived from ML-1a. To investigate how mitochondrial DNA depletion inhibits apoptosis, we investigated AKT. Both AKT and its phosphorylated form were observed only in C19, indicating that depletion of mtDNA increased protein and the active form of AKT. Treatment of C19 with LY294002, which inhibits PI-3 kinase and inhibits AKT, significantly increased apoptosis induction by TNF plus cycloheximide and eliminated phosphorylation of AKT. These results indicate that AKT activation was induced by the depletion of mtDNA and inhibited TNF-induced apoptosis.