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

• Published in: FEBS letters Vol. 472; no. 2-3; pp. 196 - 202
• Main Authors: Oka, Shin-ichi, Kamata, Hideaki, Kamata, Keiko, Yagisawa, Hitoshi, Hirata, Hajime
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 28.04.2000
• Subjects: BSO, L-buthionine-(S,R)-sulfoximine; DTNB, 5-dithiobis(2-nitrobenzoic acid); DTT, dithiothreitol; GSH, glutathione; IKK, IκB kinase; IκB kinase; N-Acetyl-L-cysteine; NAA, N-acetylalanine; NAC, N-acetyl-L-cysteine; NF-κB, nuclear factor κB; NIK, NF-κB-inducing kinase; Nuclear factor κB; Redox; 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; Tumor necrosis factor; NAC, N-acetyl-L-cysteine; GSH, glutathione; IKK, IκB kinase; TNF, tumor necrosis factor; BSO, L-buthionine-(S,R)-sulfoximine; DTNB, 5-dithiobis(2-nitrobenzoic acid); NAA, N-acetylalanine; NF-κB, nuclear factor κB; Redox; IκB kinase; DTT, dithiothreitol; TRAF2, TNF receptor-associated factor 2; SDS–PAGE, sodium dodecyl sulfate–polyacrylamide gel electrophoresis; Tumor necrosis factor; TRADD, TNF receptor-associated death domain protein; N-Acetyl-L-cysteine; ROS, reactive oxygen species; NIK, NF-κB-inducing kinase; Nuclear factor κB
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(00)01464-2

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.