Linked Life Data

12665479

Source:http://linkedlifedata.com/resource/pubmed/id/12665479

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-3-31
pubmed:abstractText
There is increasing evidence that apoptotic and necrotic hepatocyte death following endotoxin-induced liver injury act as signals for leukocyte sequestration in the liver vasculature. p53 has been implicated to promote apoptosis through trans-activation and down-regulation of specific pro- and anti-apoptotic genes. Here, we report that inhibition of p53 decreases apoptotic and necrotic tissue injury as well as inflammatory cell response. Sprague-Dawley rats were injected intraperitoneally with 2.2 mg/kg pifithrin-alpha (PFT), a p53-inactivating agent, or the vehicle DMSO 30 min before intravenous exposure to lipopolysaccharide (LPS). In vehicle-pretreated animals, LPS induced significant apoptosis and necrosis of hepatocytes, which was associated with intrahepatic leukocyte recruitment, microvascular dysfunction, and enzyme release. Inhibition of p53 effectively attenuated (P<0.05) hepatocellular apoptosis and necrosis, but also reduced leukocyte recruitment and microvascular dysfunction. Western blot analysis revealed that PFT lowered the nuclear-to-cytoplasmic p53 ratio and reduced both activation of NF-kappaB and cleavage of procaspase 3 (P<0.05). In parallel, immunohistochemistry of PFT-pretreated, but not vehicle-pretreated, endotoxic animals exhibited nuclear p53 exclusion and reduced NF-kappaB p65 staining. This indicates that p53 mediates, at least in part, LPS-associated apoptosis and contributes to inflammatory endotoxic tissue injury through leukocyte activation and intraorgan sequestration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
660-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12665479-Animals, pubmed-meshheading:12665479-Apoptosis, pubmed-meshheading:12665479-Benzothiazoles, pubmed-meshheading:12665479-Blotting, Western, pubmed-meshheading:12665479-Caspase 3, pubmed-meshheading:12665479-Caspases, pubmed-meshheading:12665479-Cell Nucleus, pubmed-meshheading:12665479-Cytoplasm, pubmed-meshheading:12665479-Female, pubmed-meshheading:12665479-Immunohistochemistry, pubmed-meshheading:12665479-Lipopolysaccharides, pubmed-meshheading:12665479-Liver, pubmed-meshheading:12665479-Male, pubmed-meshheading:12665479-Microscopy, Fluorescence, pubmed-meshheading:12665479-NF-kappa B, pubmed-meshheading:12665479-Necrosis, pubmed-meshheading:12665479-Rats, pubmed-meshheading:12665479-Rats, Sprague-Dawley, pubmed-meshheading:12665479-Thiazoles, pubmed-meshheading:12665479-Toluene, pubmed-meshheading:12665479-Transaminases, pubmed-meshheading:12665479-Tumor Suppressor Protein p53
pubmed:year
2003
pubmed:articleTitle
Inhibition of p53 protects liver tissue against endotoxin-induced apoptotic and necrotic cell death.
pubmed:affiliation
Institute for Clinical and Experimental Surgery, University of Saarland, D-66421 Homburg/Saar, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't