RGD Reference Report - Acetaldehyde inhibits NF-kappaB activation through IkappaBalpha preservation in rat Kupffer cells. - Rat Genome Database

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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.
RGD ID: 2298880
Pubmed: PMID:9918814   (View Abstract at PubMed)
DOI: DOI:10.1006/bbrc.1998.9863   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
acetaldehyde metabolic process  IEP 2298880 RGD 
cellular response to lipopolysaccharide  IEP 2298880 RGD 
cytoplasmic sequestering of NF-kappaB  IMP 2298880 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
NF-kappaB binding  ICGO:00072532298880 RGD 
sequence-specific DNA binding  IDA 2298880 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nfkbia  (NFKB inhibitor alpha)
Rela  (RELA proto-oncogene, NF-kB subunit)


Additional Information