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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3 Pt 1
pubmed:dateCreated
2001-3-20
pubmed:abstractText
Reactive oxygen species are strongly implicated in diaphragmatic dysfunction during sepsis. We investigated whether the heme oxygenase (HO) pathway, which is a powerful protective cellular system, protects the diaphragm against oxidative stress and contractile failure during sepsis. A basal expression of both the inducible and constitutive HO protein isoforms (HO-1 and HO-2, respectively) was found in the diaphragm. Enhanced HO-1 expression in diaphragmatic myocytes was observed 24 h after Escherichia coli endotoxin (lipopolysaccharide, LPS) inoculation and remained elevated for at least 96 h. Enhanced HO-1 expression was also observed in the rectus abdominis and soleus muscles and in the left ventricular myocardium of endotoxemic animals. Diaphragmatic HO-2 expression was not modified by endotoxin. Diaphragmatic HO activity exhibited a biphasic time course characterized by a transient decrease during the first 12 h followed by a significant increase at 24 h, corresponding to HO-1 induction. Diaphragmatic force was significantly reduced 24 h after LPS, concomitantly with muscular oxidative stress. Administation of an inhibitor of heme oxygenase activity, zinc protoporphyrin IX (ZnPP-IX), further impaired muscular oxidative stress and contractile failure. By contrast, increased levels of HO-1 expression obtained by pretreatment of rats with hemin, a powerful inducer of HO-1, completely prevented LPS-mediated diaphragmatic oxidative stress and contractile failure. This protective effect was reversed by ZnPP-IX. These results show an important protective role for the HO pathway against sepsis-induced diaphragmatic dysfunction, which could be related to its antioxidant properties.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1073-449X
pubmed:author
pubmed:issnType
Print
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
753-61
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Protective role of heme oxygenases against endotoxin-induced diaphragmatic dysfunction in rats.
pubmed:affiliation
Institut National de la Santé et de la Recherche Médicale U408, Faculté Xavier Bichat, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't