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

TY - JOUR

T1 - N-Acetylcysteine suppresses TNF-induced NF-κB activation through inhibition of IκB kinases

AU - Oka, Shin Ichi

AU - Kamata, Hideaki

AU - Kamata, Keiko

AU - Yagisawa, Hitoshi

AU - Hirata, Hajime

N1 - Funding Information: We are grateful to Dr. David Goeddel for the gift of plasmids expressing TRADD, TRAF2, NIK, IKKα and IKKβ, and to Dr. Makoto Nakanishi for the gift of plasmid expressing p65. This work was supported by Grant-in-Aid for Encouragement of Young Scientists 08780746 from the Ministry of Education, Science, Sports and Culture of Japan, and grants from the Tokyo Biochemical Research Foundation and the Brain Science Foundation.

PY - 2000/4/28

Y1 - 2000/4/28

N2 - 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.

AB - 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.

KW - IκB kinase

KW - N-Acetyl-L-cysteine

KW - Nuclear factor κB

KW - Redox

KW - Tumor necrosis factor

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U2 - https://doi.org/10.1016/S0014-5793(00)01464-2

DO - https://doi.org/10.1016/S0014-5793(00)01464-2

M3 - Article

C2 - 10788610

SN - 0014-5793

VL - 472

SP - 196

EP - 202

JO - FEBS Letters

JF - FEBS Letters

IS - 2-3

ER -