Linked Life Data

12958018

Source:http://linkedlifedata.com/resource/pubmed/id/12958018

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-1-12
pubmed:abstractText
Mechanisms of alcoholic pancreatitis remain unknown. Previously, we showed that ethanol feeding sensitizes rats to pancreatitis caused by CCK-8, at least in part, by augmenting activation of the proinflammatory transcription factor NF-kappaB. To elucidate the mechanism of sensitization, here we investigate the effect of ethanol on Ca(2+)- and PKC-mediated pathways of CCK-induced NF-kappaB activation using an in vitro system of rat pancreatic acini incubated with ethanol. Ethanol augmented CCK-8-induced activation of NF-kappaB, similar to our in vivo findings with ethanol-fed rats. In contrast, ethanol prevented NF-kappaB activation caused by thapsigargin, an agent that mobilizes intracellular Ca(2+) bypassing the receptor. Pharmacological analysis showed that NF-kappaB activation by thapsigargin but not by CCK-8 is mediated through the calcineurin pathway and that the inhibitory effect of ethanol on the thapsigargin-induced NF-kappaB activation could be through inhibiting this pathway. Ethanol augmented NF-kappaB activation induced by the phorbol ester PMA, a direct activator of PKC. Inhibitory analysis demonstrated that Ca(2+)-independent (novel and/or atypical) PKC isoforms are involved in NF-kappaB activation induced by both CCK-8 and PMA in cells treated and not treated with ethanol. The results indicate that ethanol differentially affects the Ca(2+)/calcineurin- and PKC-mediated pathways of NF-kappaB activation in pancreatic acinar cells. These effects may play a role in the ability of ethanol to sensitize pancreas to the inflammatory response and pancreatitis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G204-13
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Ethanol differentially regulates NF-kappaB activation in pancreatic acinar cells through calcium and protein kinase C pathways.
pubmed:affiliation
UCLA/VA Greater Los Angeles Healthcare System, West Los Angeles Center, Los Angeles, CA 90073, USA. agukovsk@ucla.edu
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.