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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."xsd:string
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http://purl.uniprot.org/citations/9918814http://purl.uniprot.org/core/author"Thomas P."xsd:string
http://purl.uniprot.org/citations/9918814http://purl.uniprot.org/core/author"Nanji A.A."xsd:string
http://purl.uniprot.org/citations/9918814http://purl.uniprot.org/core/author"Jokelainen K."xsd:string
http://purl.uniprot.org/citations/9918814http://purl.uniprot.org/core/author"Lindros K."xsd:string
http://purl.uniprot.org/citations/9918814http://purl.uniprot.org/core/date"1998"xsd:gYear
http://purl.uniprot.org/citations/9918814http://purl.uniprot.org/core/name"Biochem Biophys Res Commun"xsd:string
http://purl.uniprot.org/citations/9918814http://purl.uniprot.org/core/pages"834-836"xsd:string
http://purl.uniprot.org/citations/9918814http://purl.uniprot.org/core/title"Acetaldehyde inhibits NF-kappaB activation through IkappaBalpha preservation in rat Kupffer cells."xsd:string
http://purl.uniprot.org/citations/9918814http://purl.uniprot.org/core/volume"253"xsd:string
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