Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-8-23
pubmed:abstractText
Using monolayers of human intestinal (Caco-2) cells, we found that oxidants and ethanol damage the cytoskeleton and disrupt barrier integrity; epidermal growth factor (EGF) prevents damage by enhancement of protein kinase C (PKC) activity and translocation of the PKC-beta1 isoform. To see if PKC-beta1 mediates EGF protection, cells were transfected to stably over- or underexpress PKC-beta1. Transfected monolayers were preincubated with low or high doses of EGF (1 or 10 ng/ml) or 1-oleoyl-2-acetyl-sn-glycerol [OAG; a PKC activator (0.01 or 50 microM)] before treatment with oxidant (0.5 mM H(2)O(2)). Only in monolayers overexpressing PKC-beta1 (3.1-fold) did low doses of EGF or OAG initiate protection, increase tubulin polymerization (assessed by quantitative immunoblotting) and microtubule architectural integrity (laser scanning confocal microscopy), maintain normal barrier permeability (fluorescein sulfonic acid clearance), and cause redistribution of PKC-beta1 from cytosolic pools into membrane and/or cytoskeletal fractions (assessed by immunoblotting), thus indicating PKC-beta1 activation. Antisense inhibition of PKC-beta1 expression (-90%) prevented these changes and abolished EGF protection. We conclude that EGF protection against oxidants requires PKC-beta1 isoform activation. This mechanism may be useful for development of novel therapies for the treatment of inflammatory gastrointestinal disorders including inflammatory bowel disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G833-47
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
PKC-beta1 mediates EGF protection of microtubules and barrier of intestinal monolayers against oxidants.
pubmed:affiliation
Division of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois 60612, USA. ali_banan@rush.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't