Schuster Norbert, Bender Herdis, Rössler Oliver G, Philippi Anja, Dünker Nicole, Thiel Gerald, Krieglstein Kerstin
Department of Anatomy and Cell Biology, Medical Faculty, University of Saarland, Homburg/Saar, Germany.
J Neurosci Res. 2003 Aug 1;73(3):324-33. doi: 10.1002/jnr.10666.
As shown previously, transforming growth factor-beta (TGF-beta) 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-beta with tumor necrosis factor-alpha (TNF-alpha) 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-beta seemed to be more efficient at inducing a release in cytochrome c from mitochondria than TNF-alpha. This might be the consequence of decreased Bcl-xL levels observed in cells treated with TGF-beta but not with TNF-alpha. Both factors stimulated caspase-3 activity, which could be inhibited by caspase-8 or caspase-9 inhibitors. Therefore, we conclude that TNF-alpha and TGF-beta affect partially common pathways but also regulate different steps in the apoptotic cascade.
如前所示，转化生长因子-β（TGF-β）在神经系统发育性细胞死亡期间发挥重要作用。与神经元一样，少突胶质细胞过量生成并通过凋亡被清除。本研究旨在探讨TGF-β与肿瘤坏死因子-α（TNF-α）在少突胶质前体细胞死亡调控中的可能相互作用，并分析潜在的信号传导机制。我们发现这两种因子均可独立诱导凋亡，但共同应用时会协同作用。对信号事件的研究揭示了JNK途径在凋亡诱导过程中的重要作用。TGF-β似乎比TNF-α更有效地诱导细胞色素c从线粒体中释放。这可能是在用TGF-β而非TNF-α处理的细胞中观察到Bcl-xL水平降低的结果。两种因子均刺激了caspase-3活性，这可被caspase-8或caspase-9抑制剂抑制。因此，我们得出结论，TNF-α和TGF-β部分影响共同途径，但也调节凋亡级联反应中的不同步骤。
