TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death (Mol Cell, 2007, 26:675-687)

報告日期: 2008/05/27
報告時間: 16:05/16:55
報告學生: 黃怡璇
講評老師: 陳麗玉

TNF-Induced activation of the Nox1 NADPH oxidase and its role in the Induction of necrotic cell death

Molecular Cell 26, 675–687 (2007)


Commentator:陳麗玉 老師

Date2008/05/27 , 16:10~17:00 pm

PlaceRoom 602



Tumor necrosis factor (TNF) is a pleiotropic inflammatory cytokine and plays a critical role in diverse cellular events, including cell proliferation, differentiation, apoptosis, and necrosis. Necrotic cell death has been proposed to involve in reactive oxygen species (ROS), ROS-mediated JNK activation, and Nox1 activation to produce caspase-independent cell death. However, the mechanism of TNF-initiated caspase-independent necrotic cell death is largely unknown. Here, the authors report that Nox1 NADPH oxidase is activated during TNF-induced necrotic cell death by forming a complex with TRADD, RIP1, and Rac1. Which of them, RIP1 is essential for recruiting Nox1 to the complex and interactions of NOXO1 with TRADD and RIP1 are critical for the activation of Nox1. Additionally, the phenomena that blocks Nox1 activation and significant increase of cell survival are observed when block TRADD or Rac1 via different dominant-negative factors (TRADD P-A or N17Rac1). Surprisingly, the N17Rac1 (a dominant-negative molecule) significantly reduced the amount of O2- produced in response to TNF. These data imply that Nox1 activation induces ROS to stimulate sustained JNK activation and result in eventual cell death. Sustained JNK activation occurs in response to the production of O2- generated downstream of TNF and that prolonged JNK activation contributes to caspase independent necrotic cell death induced by TNF.



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