TNF-receptor associated factor 6-deficient fibroblast is sensitive to the TNF-α-induced cell death: Involvement of reactive oxygen species

Daiju Ichikawa, Megumi Funakoshi-Tago, Eriko Aizu-Yokota, Yoshiko Sonoda, Jun ichiro Inoue, Tadashi Kasahara

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) has mainly been involved in signaling from CD40 and IL-1 receptor family. While TNF-α exerts various biological effects including cell death, the role of TRAF6 in the TNF-α signaling remains to be unclear. Here, we demonstrated that murine embryonic fibroblasts (MEFs) derived from TRAF6 knockout (TRAF6KO) mice have increased sensitivity to actinomycin D plus TNF-α-induced cell death compared with wild-type MEF. Reactive oxygen species (ROS) were accumulated more in TRAF6KO MEF than in wild-type MEF. An antioxidant, butylated hydroxyanisole (BHA) completely inhibited TNF-α-induced cell death and DNA fragmentation. Thus, the TNF-α-induced cell death in TRAF6KO MEF was ROS-dependent. Reconstitution of full-length TRAF6 but not N-terminal-deleted TRAF6 constructs in TRAF6KO MEF reversed TNF-α-induced cell death, ROS accumulation, and DNA fragmentation completely. Thus, we concluded that resistance against TNF-α-induced cell death is rendered by TRAF6, which regulates ROS accumulation.

Original languageEnglish
Pages (from-to)93-98
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume351
Issue number1
DOIs
Publication statusPublished - 2006 Dec 8

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Keywords

  • Actinomycin D
  • Antioxidant
  • BHA
  • Cell death
  • MEF
  • ROS
  • TNF-α
  • TRAF6
  • TRAF6KO

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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