N‐Acetylcysteine suppresses TNF‐induced NF‐κB activation through inhibition of IκB kinases

FEBS Letters

Kamata, Keiko¹  Kamata, Hideaki¹  Hirata, Hajime¹  Yagisawa, Hitoshi¹  Oka, Shin-ichi¹ 

[1] Department of Life Science, Faculty of Science, Himeji Institute of Technology, Kamigori-chou, Akoh-gun, Hyogo 678-1297, Japan

关键词: N-Acetyl-L-cysteine;    Tumor necrosis factor;    Nuclear factor κB;    IκB kinase;    Redox;    BSO;    L-buthionine-(S;    R)-sulfoximine;    DTNB;    5-dithiobis(2-nitrobenzoic acid);    DTT;    dithiothreitol;    GSH;    glutathione;    IKK;    IκB kinase;    NAA;    N-acetylalanine;    NAC;    N-acetyl-L-cysteine;    NF-κB;    nuclear factor κB;    NIK;    NF-κB-inducing kinase;    ROS;    reactive oxygen species;    SDS–PAGE;    sodium dodecyl sulfate–polyacrylamide gel electrophoresis;    TNF;    tumor necrosis factor;    TRADD;    TNF receptor-associated death domain protein;    TRAF2;    TNF receptor-associated factor 2;   

DOI  :  10.1016/S0014-5793(00)01464-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Here, we used a reductant, N-acetyl-L-cysteine (NAC), to investigate the redox-sensitive step(s) in the signalling pathway from the tumor necrosis factor (TNF) receptor to nuclear factor κB (NF-κB). We found that NAC suppressed NF-κB activation triggered by TNF or by overexpression of either the TNF receptor-associated death domain protein, TNF receptor-associated factor 2, NF-κB-inducing kinase (NIK), or IκB kinases (IKKα and IKKβ). NAC also suppressed the TNF-induced activation of IKKα and IKKβ, phosphorylation and degradation of IκB, and nuclear translocation of NF-κB. Furthermore, NAC suppressed the activation of IKKα and IKKβ triggered by the overexpression of NIK. These results indicate that IKKα and IKKβ are subject to redox regulation in the cells, and that NAC inhibits NF-κB activation through the suppression of these kinases.

【 授权许可】

Unknown