Bessette Barbara, Durand Karine, Giraud Stéphanie, Bégaud Gaëlle, Mathonnet Muriel, Lalloué Fabrice
University of Limoges, EA3842, 'Cellular Homeostasis and Pathology', Faculty of Medicine, 87025 Limoges Cedex;
Exp Ther Med. 2012 May;3(5):873-877. doi: 10.3892/etm.2012.480. Epub 2012 Feb 13.
p75(NTR), a member of the tumor necrosis factor superfamily, plays a key role in numerous physiological processes, including cell survival or apoptosis. Yet, the associated signaling pathways remain poorly understood. Similar to Notch, γ-secretase cleavage is implicated in the p75(NTR) signaling pathway leading to nuclear translocation of the intracellular domain and cell death. Fas receptor activation was found to promote cell death apoptosis in several cell lines. The goal of this study was to determine the respective role of p75(NTR) and Notch in the resistance to Fas-induced apoptosis in the U-87 MG glioblastoma cell line. Using the γ-secretase inhibitor, we investigated the modulation of Fas-induced apoptosis dependent on p75(NTR)-Fas receptor interaction. Whereas the U-87 MG cells expressed the Fas receptor at the cell membrane, apoptosis induced by Fas activation was decreased by the γ-secretase inhibitor. These data suggest that γ-secretase is implicated in p75(NTR) and Fas interaction leading to cell death signaling.
p75神经营养因子受体（p75(NTR)）是肿瘤坏死因子超家族的成员之一，在包括细胞存活或凋亡在内的众多生理过程中发挥关键作用。然而，与之相关的信号通路仍未被充分了解。与Notch类似，γ-分泌酶切割参与p75(NTR)信号通路，导致细胞内结构域的核转位和细胞死亡。研究发现Fas受体激活在几种细胞系中可促进细胞凋亡。本研究的目的是确定p75(NTR)和Notch在U-87 MG胶质母细胞瘤细胞系对Fas诱导凋亡的抗性中各自的作用。使用γ-分泌酶抑制剂，我们研究了依赖p75(NTR)-Fas受体相互作用的Fas诱导凋亡的调节。虽然U-87 MG细胞在细胞膜上表达Fas受体，但γ-分泌酶抑制剂可降低Fas激活诱导的凋亡。这些数据表明，γ-分泌酶参与p75(NTR)与Fas的相互作用，从而导致细胞死亡信号传导。
