Bender Herdis, Wang Ziyuan, Schuster Norbert, Krieglstein Kerstin
Center of Anatomy, University of Goettingen, Goettingen, Germany.
J Neurosci Res. 2004 Feb 1;75(3):344-52. doi: 10.1002/jnr.10856.
Transforming growth factor-beta (TGF-beta) plays an important role during the period of developmental cell death in the nervous system. Using the oligodendroglial precursor cell line OLI-neu, we have previously established an in vitro system to analyze TGF-beta-mediated cell death on the molecular level. We could show that the Krüppel-like Zn-finger transcription factor TIEG1 was up-regulated after TGF-beta stimulation of OLI-neu cells and mimicked TGF-beta effects in these cells; i.e., overexpression of TIEG1 in OLI-neu cells induced apoptosis as shown by apoptosis ELISA, DNA fragmentation, and caspases-3 activation. The apoptotic pathway seemed to be initiated by repressing the expression of the antiapoptotic protein Bcl-XL. In contrast, the reporter activity of a SMAD consensus promoter was induced, whereas the promoter activity of the inhibitory SMAD7 was reduced, suggesting that SMAD-dependent TGF-beta responses, such as TGF-beta-induced apoptosis, are enhanced in the presence of TIEG1.
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。利用少突胶质前体细胞系OLI-neu，我们先前建立了一个体外系统，用于在分子水平分析TGF-β介导的细胞死亡。我们发现，在TGF-β刺激OLI-neu细胞后，类Krüppel锌指转录因子TIEG1上调，并在这些细胞中模拟了TGF-β的作用；即，如凋亡ELISA、DNA片段化和半胱天冬酶-3激活所示，TIEG1在OLI-neu细胞中的过表达诱导了细胞凋亡。凋亡途径似乎是通过抑制抗凋亡蛋白Bcl-XL的表达而启动的。相反，SMAD共有启动子的报告基因活性被诱导，而抑制性SMAD7的启动子活性降低，这表明在存在TIEG1的情况下，SMAD依赖的TGF-β反应，如TGF-β诱导的细胞凋亡，会增强。
