Differential regulation of the mitochondrial and death receptor pathways in neural stem cells
Differential regulation of the mitochondrial and death receptor pathways in neural stem cells
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DOI：
10.1111/j.0953-816x.2004.03391.x
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发表时间：
2004-05-01
影响因子：
3.4
通讯作者：
Ceccatelli, S
中科院分区：
文献类型：
--
作者：
Tamm, C;Robertson, JD;Ceccatelli, S
尽管对神经干细胞（NSC）研究的兴趣越来越大，但对这些细胞中细胞死亡途径的生化调控知之甚少。在这里，我们证明，使用鼠源性多能C17.2神经干细胞，细胞发生凋亡的刺激，如氧化应激诱导的2，3-二甲氧基-1，4-萘醌（DMNQ）的细胞死亡。特别是，处理后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，但激动性Fas mAb处理未能诱导凋亡。Fas处理激活细胞外信号调节蛋白激酶（ERK）途径，这可能具有抗凋亡以及生长刺激作用。结合，我们的研究结果表明，虽然神经干细胞是敏感的细胞毒性刺激，涉及参与线粒体，Fas治疗不诱导死亡，并可能有一个替代的作用。
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.