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首页> 外文期刊>The European Journal of Neuroscience >Differential regulation of the mitochondrial and death receptor pathways in neural stem cells.
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Differential regulation of the mitochondrial and death receptor pathways in neural stem cells.

机译:神经干细胞中线粒体和死亡受体途径的差异调节。

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Abstract Despite an increasing interest in neural stem cell (NSC) research, relatively little is known about the biochemical regulation of cell death pathways in these cells. We demonstrate here, using murine-derived multipotent C17.2 NSCs, that cells undergo mitochondria-mediated cell death in response to apoptotic stimuli such as oxidative stress induced by 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). In particular, treated cells exhibited apoptotic features, including Bax translocation, cytochrome c release, activation of caspase-9 and -3, chromatin condensation and DNA fragmentation. Although C17.2 cells possess the Fas receptor and express procaspase-8, agonistic Fas mAb treatment failed to induce apoptosis. Fas treatment activated the extracellular signal-regulated protein kinase (ERK) pathway, which may have an antiapoptotic as well as a growth stimulating role. Combined, our findings indicate that while NSCs are sensitive to cytotoxic stimuli that involve an engagement of mitochondria, Fas treatment does not induce death and may have an alternative role.
机译:摘要尽管人们对神经干细胞(NSC)的研究兴趣日益浓厚,但对这些细胞中细胞死亡途径的生化调节知之甚少。我们在这里证明,使用小鼠衍生的多能C17.2 NSC,细胞经历线粒体介导的细胞死亡,以响应凋亡刺激,例如由2,3-二甲氧基-1,4-萘醌(DMNQ)引起的氧化应激。特别地,处理的细胞表现出凋亡特征,包括Bax易位,细胞色素c释放,caspase-9和-3的活化,染色质浓缩和DNA片段化。尽管C17.2细胞具有Fas受体并表达procaspase-8,但是激动性Fas mAb处理无法诱导细胞凋亡。 Fas治疗激活了细胞外信号调节蛋白激酶(ERK)途径,该途径可能具有抗凋亡以及促进生长的作用。综合起来,我们的发现表明,尽管NSC对涉及线粒体参与的细胞毒性刺激敏感,但Fas治疗不会诱发死亡,并且可能具有替代作用。

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