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N ‐Acetylcysteine suppresses TNF‐induced NF‐κB activation through inhibition of IκB kinases
Author(s) -
Oka Shin-ichi,
Kamata Hideaki,
Kamata Keiko,
Yagisawa Hitoshi,
Hirata Hajime
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01464-2
Subject(s) - iκb kinase , kinase , phosphorylation , nf κb , tumor necrosis factor alpha , chemistry , iκbα , microbiology and biotechnology , signal transduction , receptor , acetylcysteine , cancer research , biochemistry , biology , endocrinology , antioxidant
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.