Document Detail


Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation.
MedLine Citation:
PMID:  10487768     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  104     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1999 Sep 
Date Detail:
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    
Other Details:
Languages:  eng     Pagination:  541-9     Citation Subset:  AIM; IM    
Affiliation:
Department of General Surgery, University of Maastricht, 6200 MD Maastricht, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Chloromethyl Ketones / administration & dosage,  pharmacology,  therapeutic use*
Animals
Apoptosis / drug effects*
Blood Urea Nitrogen
Caspases / metabolism
Chemotaxis, Leukocyte
Cysteine Proteinase Inhibitors / administration & dosage,  pharmacology,  therapeutic use*
Cytokines*
Depression, Chemical
Drug Administration Schedule
Epidermal Growth Factor / pharmacology
Humans
In Situ Nick-End Labeling
Insulin-Like Growth Factor I / administration & dosage,  pharmacology,  therapeutic use*
Ischemia / complications,  pathology*
Kidney / blood supply*,  pathology
Male
Mice
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*
Chemical
Reg. No./Substance:
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 1.11.1.7/Peroxidase; EC 3.4.22.-/Caspases
Comments/Corrections

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