|Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation.|
|PMID: 10487768 Owner: NLM Status: MEDLINE|
|Ischemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered to be the most important cause of tissue injury in organs subjected to ischemia. The mechanism that triggers inflammation and organ injury after ischemia remains to be elucidated, although different causes have been postulated. We investigated the role of apoptosis in the induction of inflammation and organ damage after renal ischemia. Using a murine model, we demonstrate a relationship between apoptosis and subsequent inflammation. At the time of reperfusion, administration of the antiapoptotic agents IGF-1 and ZVAD-fmk (a caspase inactivator) prevented the early onset of not only renal apoptosis, but also inflammation and tissue injury. Conversely, when the antiapoptotic agents were administered after onset of apoptosis, these protective effects were completely abrogated. The presence of apoptosis was directly correlated with posttranslational processing of the endothelial monocyte-activating polypeptide II (EMAP-II), which may explain apoptosis-induced influx and sequestration of leukocytes in the reperfused kidney. These results strongly suggest that apoptosis is a crucial event that can initiate reperfusion-induced inflammation and subsequent tissue injury. The newly described pathophysiological insights provide important opportunities to effectively prevent clinical manifestations of reperfusion injury in the kidney, and potentially in other organs.|
|M A Daemen; C van 't Veer; G Denecker; V H Heemskerk; T G Wolfs; M Clauss; P Vandenabeele; W A Buurman|
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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: The Journal of clinical investigation Volume: 104 ISSN: 0021-9738 ISO Abbreviation: J. Clin. Invest. Publication Date: 1999 Sep|
|Created Date: 1999-10-04 Completed Date: 1999-10-04 Revised Date: 2013-04-18|
Medline Journal Info:
|Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: UNITED STATES|
|Languages: eng Pagination: 541-9 Citation Subset: AIM; IM|
|Department of General Surgery, University of Maastricht, 6200 MD Maastricht, The Netherlands.|
|APA/MLA Format Download EndNote Download BibTex|
Amino Acid Chloromethyl Ketones
administration & dosage,
Apoptosis / drug effects*
Blood Urea Nitrogen
Caspases / metabolism
Cysteine Proteinase Inhibitors / administration & dosage, pharmacology, therapeutic use*
Drug Administration Schedule
Epidermal Growth Factor / pharmacology
In Situ Nick-End Labeling
Insulin-Like Growth Factor I / administration & dosage, pharmacology, therapeutic use*
Ischemia / complications, pathology*
Kidney / blood supply*, pathology
Neoplasm Proteins / metabolism
Nephritis / etiology, prevention & control*
Peroxidase / blood
Protein Processing, Post-Translational
RNA-Binding Proteins / metabolism
Recombinant Proteins / pharmacology
Reperfusion Injury / pathology, prevention & control*
|0/Amino Acid Chloromethyl Ketones; 0/Cysteine Proteinase Inhibitors; 0/Cytokines; 0/Neoplasm Proteins; 0/RNA-Binding Proteins; 0/Recombinant Proteins; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 0/small inducible cytokine subfamily E, member 1; 62229-50-9/Epidermal Growth Factor; 67763-96-6/Insulin-Like Growth Factor I; EC 18.104.22.168/Peroxidase; EC 3.4.22.-/Caspases|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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