Document Detail


Activation of the ubiquitin proteolytic pathway in human septic heart and diaphragm.
MedLine Citation:
PMID:  19375358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Mechanisms of sepsis-induced myocardial and diaphragmatic alteration are multiple and remain largely unknown, particularly in humans. In the present study, we compared the inducible nitric oxide synthase (NOS-2) expression, the peroxynitrite production and the expression and activation of the ubiquitin proteolytic pathway in the wall of the 4 cardiac chambers, in the diaphragm, and in the rectus abdominis.
PATIENTS: Seven patients who died from septic shock associated with a myocardial depression and 5 nonseptic (control) patients.
MEASUREMENTS AND RESULTS: We evaluated protein expression by Western blot. Nitrotyrosin and ubiquitin residues were localized by immunofluorescence. NOS-2, nitrated proteins, free ubiquitin, and ubiquitinated proteins are overexpressed in the wall of the four cardiac cavities, in the diaphragm and in the rectus abdominis of septic patients at a similar level. Ubiquitinated proteins with a molecular mass of 50, 35, 30, and 25 kD were consistently detected in heart, diaphragm, and rectus abdominis of septic shock patients but lacking in nonseptic patients. In situ immunolabelling of ubiquitin showed a colocalisation with nitrotyrosine residues at the sarcomeric level of cardiac myocytes in septic patients.
CONCLUSIONS: This study showed the first evidence for the activation of the proteolytic ubiquitin-proteasome pathway in human heart and diaphragm in septic shock.
Authors:
Christophe Rabuel; Jane-Lise Samuel; Brice Lortat-Jacob; Françoise Marotte; Sophie Lanone; Christine Keyser; Arrigo Lessana; Didier Payen; Alexandre Mebazaa
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Publication Detail:
Type:  Journal Article     Date:  2009-04-16
Journal Detail:
Title:  Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology     Volume:  19     ISSN:  1879-1336     ISO Abbreviation:  Cardiovasc. Pathol.     Publication Date:    2010 May-Jun
Date Detail:
Created Date:  2010-05-10     Completed Date:  2010-08-13     Revised Date:  2011-10-27    
Medline Journal Info:
Nlm Unique ID:  9212060     Medline TA:  Cardiovasc Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  158-64     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Anesthesiology and Critical Care Medicine, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Blotting, Western
Diaphragm / metabolism*,  pathology
Female
Fluorescent Antibody Technique
Humans
Male
Middle Aged
Myocardium / metabolism*,  pathology
Nitric Oxide Synthase Type II / metabolism
Peroxynitrous Acid / metabolism
Rectus Abdominis / metabolism,  pathology
Shock, Septic / metabolism*,  pathology
Signal Transduction
Ubiquitin / metabolism*
Ubiquitinated Proteins / metabolism*
Ubiquitination
Chemical
Reg. No./Substance:
0/Ubiquitin; 0/Ubiquitinated Proteins; 14691-52-2/Peroxynitrous Acid; EC 1.14.13.39/NOS2 protein, human; EC 1.14.13.39/Nitric Oxide Synthase Type II

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