Transforming growth factor‐β and tumor necrosis factor‐α cooperate to induce apoptosis in the oligodendroglial cell line OLI‐neu
Transforming growth factor‐β and tumor necrosis factor‐α cooperate to induce apoptosis in the oligodendroglial cell line OLI‐neu
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DOI：
10.1002/jnr.10666
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发表时间：
2003-08
影响因子：
4.2
通讯作者：
N. Schuster;Herdis Bender;O. G. Rössler;A. Philippi;N. Dünker;G. Thiel;K. Krieglstein
中科院分区：
文献类型：
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作者：
N. Schuster;Herdis Bender;O. G. Rössler;A. Philippi;N. Dünker;G. Thiel;K. Krieglstein
如前所述，转化生长因子- β (TGF - β)在神经系统发育细胞死亡过程中起重要作用。与神经元一样，少突胶质细胞产生过多，并通过凋亡消除。本研究旨在探讨TGF - β与肿瘤坏死因子α (TNF - α)在调节少突胶质前体细胞死亡中的可能相互作用，并分析其潜在的信号传导机制。我们发现这两种因子分别诱导细胞凋亡，但当它们共同作用时却相互配合。对信号事件的研究揭示了JNK通路在诱导细胞凋亡过程中的重要作用。TGF‐β在诱导线粒体释放细胞色素c方面似乎比TNF‐α更有效。这可能是在TGF - β处理的细胞中观察到的Bcl - xL水平下降的结果，而TNF - α没有。这两种因素均刺激caspase‐3活性，而caspase‐8或caspase‐9抑制剂可抑制caspase‐3活性。因此，我们得出结论，TNF - α和TGF - β部分影响共同的途径，但也调节凋亡级联的不同步骤。©2003 Wiley‐Liss, Inc。
As shown previously, transforming growth factor‐β (TGF‐β) plays an important role during the period of developmental cell death in the nervous system. As with neurons, oligodendrocytes are generated in excess and eliminated by apoptosis. The present study was aimed at investigating the possible interaction of TGF‐β with tumor necrosis factor‐α (TNF‐α) in the regulation of cell death in oligodendroglial precursor cells and analyzing the underlying signaling mechanisms. We show that both factors induce apoptosis independently, but cooperate when applied together. The investigation of the signaling events revealed an important role of the JNK pathway during induction of apoptosis. TGF‐β seemed to be more efficient at inducing a release in cytochrome c from mitochondria than TNF‐α. This might be the consequence of decreased Bcl‐xL levels observed in cells treated with TGF‐β but not with TNF‐α. Both factors stimulated caspase‐3 activity, which could be inhibited by caspase‐8 or caspase‐9 inhibitors. Therefore, we conclude that TNF‐α and TGF‐β affect partially common pathways but also regulate different steps in the apoptotic cascade. © 2003 Wiley‐Liss, Inc.