Linked Life Data

9886984

Source:http://linkedlifedata.com/resource/pubmed/id/9886984

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1 Pt 1
pubmed:dateCreated
1999-3-9
pubmed:abstractText
Ethanol impairs hormone-stimulated cAMP production in a number of cell types, yet the effects of ethanol on downstream responses mediated by cAMP-dependent protein kinase (PKA) are not understood. Here we have investigated the effects of ethanol feeding on cAMP-mediated inhibition of tumor necrosis factor-alpha (TNF-alpha) synthesis in rat Kupffer cells. Male Wistar rats were fed liquid diets containing 36% of calories as ethanol for 4 wk or were pair fed a control diet. Stimulation of cAMP production by the adenosine A2 receptor agonist 5'-(N-ethylcarboxamido)-adenosine (NECA), prostaglandin E2, or forskolin was decreased to 25% of control values in Kupffer cells isolated from ethanol-fed rats. This decrease was associated with a reduction in the quantity of immunoreactive Gsalpha protein in ethanol-fed rats, with no changes observed in Gialpha or Gbeta. TNF-alpha production was higher in ethanol-fed rats in response to stimulation with lipopolysaccharide or latex beads. Despite the profound reduction in the ability of hormone to increase cAMP production, NECA and prostaglandin E2 inhibited TNF-alpha production to an equivalent degree in Kupffer cells from ethanol- and pair-fed rats. Total activity and immuoreactive protein quantity of PKA did not differ between groups. Activation of PKA in response to a 15-min treatment with 1 microM NECA was reduced by 50% in ethanol-fed rats compared with control. Despite this reduction in activation, translocation of the catalytic subunit of PKA to the nucleus and phosphorylation of cAMP response element binding protein in response to activation were observed in Kupffer cells from both ethanol- and pair-fed rats. These data demonstrate that there is a dissociation between ethanol-induced desensitization of hormone-stimulated cAMP production in rat Kupffer cells and the downstream inhibition of TNF-alpha production mediated by cAMP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G98-G106
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9886984-Adenosine-5'-(N-ethylcarboxamide), pubmed-meshheading:9886984-Animals, pubmed-meshheading:9886984-Cell Separation, pubmed-meshheading:9886984-Cells, Cultured, pubmed-meshheading:9886984-Cyclic AMP, pubmed-meshheading:9886984-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:9886984-Dinoprostone, pubmed-meshheading:9886984-Ethanol, pubmed-meshheading:9886984-Forskolin, pubmed-meshheading:9886984-GTP-Binding Proteins, pubmed-meshheading:9886984-Hormones, pubmed-meshheading:9886984-Kupffer Cells, pubmed-meshheading:9886984-Male, pubmed-meshheading:9886984-Rats, pubmed-meshheading:9886984-Rats, Wistar, pubmed-meshheading:9886984-Receptors, Prostaglandin E, pubmed-meshheading:9886984-Receptors, Purinergic P1, pubmed-meshheading:9886984-Tumor Necrosis Factor-alpha
pubmed:year
1999
pubmed:articleTitle
Ethanol dissociates hormone-stimulated cAMP production from inhibition of TNF-alpha production in rat Kupffer cells.
pubmed:affiliation
Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't