N-acetylcysteine suppresses TNF-induced NF-kappaB activation through inhibition of IkappaB kinases.

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Oka S, Kamata H, Kamata K, Yagisawa H, Hirata H

N-acetylcysteine suppresses TNF-induced NF-kappaB activation through inhibition of IkappaB kinases.

FEBS Lett. 2000 Apr 28;472(2-3):196-202.

PubMed ID

10788610 [ View in PubMed

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Abstract

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 kappaB (NF-kappaB). We found that NAC suppressed NF-kappaB activation triggered by TNF or by overexpression of either the TNF receptor-associated death domain protein, TNF receptor-associated factor 2, NF-kappaB-inducing kinase (NIK), or IkappaB kinases (IKKalpha and IKKbeta). NAC also suppressed the TNF-induced activation of IKKalpha and IKKbeta, phosphorylation and degradation of IkappaB, and nuclear translocation of NF-kappaB. Furthermore, NAC suppressed the activation of IKKalpha and IKKbeta triggered by the overexpression of NIK. These results indicate that IKKalpha and IKKbeta are subject to redox regulation in the cells, and that NAC inhibits NF-kappaB activation through the suppression of these kinases.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Acetylcysteine	Inhibitor of nuclear factor kappa-B kinase subunit alpha	Protein	Humans	Unknown	Inhibitor	Details
Acetylcysteine	Inhibitor of nuclear factor kappa-B kinase subunit beta	Protein	Humans	Unknown	Inhibitor	Details