N-acetylcysteine suppresses TNF-induced NF-κB activation through inhibition of IκB kinases

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 kappa B (NF-kappa B). We found that NAC suppressed NF-kappa B activation triggered by TNF or by overexpression of either the TSF receptor-associated death domain protein, TNF receptor-associated factor 2, NF-kappa B-inducing kinase (NIK), or I kappa B kinases (IKK alpha and IKK beta). NAC also suppressed the TNF-induced activation of IKK alpha and IKK beta, phosphorylation and degradation of I kappa B, and nuclear translocation of NF-kappa B. Furthermore, NAC suppressed the activation of IKK alpha and IKK beta triggered by the overexpression of NIK, These results indicate that IKK alpha and IKK beta are subject to redox regulation in the cells, and that NAC inhibits NF-kappa B activation through the suppression of these kinases. (C) 2000 Federation of European Biochemical Societies.