Acetaldehyde inhibits NF-kappaB activation through IkappaBalpha preservation in rat Kupffer cells.

Authors: Jokelainen, K  Thomas, P  Lindros, K  Nanji, AA 
Citation: Jokelainen K, etal., Biochem Biophys Res Commun. 1998 Dec 30;253(3):834-6.
Pubmed: (View Article at PubMed) PMID:9918814
DOI: Full-text: DOI:10.1006/bbrc.1998.9863

BACKGROUND AND AIMS: Treatment with acetaldehyde dehydrogenase inhibitors leads to increased liver acetaldehyde levels and prevents hepatic inflammation and necrosis in ethanol-fed rats. This is accompanied by IkappaBa preservation and decreased activation of nuclear factor (NF)-kappaB. The present in vitro study was aimed to clarify whether acetaldehyde has an effect on degradation of IkappaBalpha and activation of NF-kappaB in LPS-stimulated rat Kupffer cells. METHODS: Kupffer cells were isolated from male Sprague-Dawley rats and preincubated with various concentrations of acetaldehyde (25-100 microM). Thereafter the cells were stimulated with LPS, and cytosolic and nuclear fractions were prepared. IkappaBalpha and p65 proteins and activation of NF-kappaB were evaluated. RESULTS: In LPS-stimulated rat Kupffer cells, acetaldehyde diminished proteolytic degradation of IkappaBalpha, inhibited nuclear translocation of cytosolic p65 protein, and, accordingly, markedly decreased NF-kappaB activation. CONCLUSIONS: Acetaldehyde is clearly involved in the stabilization of IkappaBalpha protein and suppression of NF-kappaB activation in rat Kupffer cells. Acetaldehyde may form an adduct with IkappaBalpha, thus making the protein less susceptible to degradation.

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CRRD ID: 2298880
Created: 2008-07-30
Species: All species
Last Modified: 2008-07-30
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.