Linked Life Data

15579512

Source:http://linkedlifedata.com/resource/pubmed/id/15579512

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-12-6
pubmed:abstractText
In previous work, it was demonstrated that apoptosis occurs in the kidney during LPS-induced acute renal failure (ARF). However, the relative importance of apoptosis in LPS-induced ARF remained unproven. Because the caspase enzyme cascade is responsible for carrying out apoptosis, it was hypothesized that treatment with a caspase inhibitor would protect mice from LPS-induced ARF. C57BL/6 mice received an injection of LPS and were treated with either the broad-spectrum caspase inhibitor z-VAD-fmk or vehicle and compared with unmanipulated mice. LPS induced a significant increase in caspase-3 activity in vehicle-treated mice, which was significantly inhibited by z-VAD. Mice that were treated with z-VAD were protected from ARF and demonstrated significantly less apoptosis as measured by both terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and DNA laddering. Although apoptosis is classically described as a noninflammatory process, z-VAD treatment significantly attenuated multiple markers of inflammation, such as renal neutrophil infiltration and renal expression of the neutrophil chemotactic factor macrophage inflammatory protein-2. Thus, caspase inhibition may protect against LPS-induced ARF not only by preventing apoptotic cell death but also by inhibiting inflammation. These data raise the possibility that apoptotic kidney cells may actually be a source of this local inflammation, contributing to subsequent nonapoptotic renal injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1046-6673
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3093-102
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Acute renal failure in endotoxemia is dependent on caspase activation.
pubmed:affiliation
Section of Nephrology, University of Chicago, MC5100, Room S511, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.