Linked Life Data

10865997

Source:http://linkedlifedata.com/resource/pubmed/id/10865997

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-7-7
pubmed:abstractText
Defects in apoptosis have been noted in signal transducer and activator of transcription (Stat) 1-null cells in vitro. The purpose of this study was to analyse the keratocyte apoptosis response that occurs in vivo in response to corneal epithelial injury in Stat 1null compared with control mice and to determine whether Stat 1null corneal fibroblasts have a defective response to death receptor activation in vitro. Corneal epithelial scrape injuries were performed in Stat 1-null and wild-type mice. Keratocyte apoptosis was monitored with the quantitative TUNEL assay and confirmed using transmission electron microscopy. Corneal fibroblast apoptosis in response to tumor necrosis factor (TNF) alpha, with and without inhibitors of nuclear factor kappa B (NF-kappaB) activation, was monitored using DNA laddering and the methylene blue assay. Significantly less keratocyte apoptosis was noted in Stat 1-null mice compared with wild-type controls. TNF alpha-induced apoptosis only occurred in wild-type mice in the presence of inhibitors of NF-kappaB activation. Corneal fibroblast TNF alpha-induced apoptosis was defective in Stat 1null corneal fibroblasts whether NF-kappaB activation was blocked or not. Stat 1 has an important role in the keratocyte apoptosis that occurs in response to corneal epithelial injury. Previous studies suggest that the defect is due to a lack of constitutive expression of caspases. This study demonstrates that this defect in apoptosis in Stat 1-null mice is present in vivo in Stat 1-null mice and suggests that Stat 1 could be a therapeutic target for transient inhibition of keratocyte apoptosis to modulate corneal wound healing.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0014-4835
pubmed:author
pubmed:issnType
Print
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
485-91
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Defective keratocyte apoptosis in response to epithelial injury in stat 1 null mice.
pubmed:affiliation
The Department of Ophthalmology, University of Washington School of Medicine, Seattle 98195-6485, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't