Linked Life Data

10463956

Source:http://linkedlifedata.com/resource/pubmed/id/10463956

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-9-17
pubmed:abstractText
It has been shown that nitric oxide (NO), synthesized by the inducible NO synthase (iNOS) expressed in the diaphragm during endotoxemia, participates in the development of muscular contractile failure. The aim of the present study was to investigate whether this deleterious action of NO was related to its effects on cellular oxidative pathways. Rats were inoculated with E. coli lipopolysaccharide (LPS) or sterile saline solution (controls) and studied at 3 and 6 h after inoculation. iNOS protein and activity could be detected in the rat diaphragm as early as 3 h after LPS, with a sustained steady-state concentration of 0.5 microM NO in the muscle associated with increased detection of hydrogen peroxide (H(2)O(2)). In vitro, the same NO concentration produced a marked increase in H(2)O(2) production by isolated control diaphragm mitochondria, thus reflecting a higher intramitochondrial concentration of nondiffusible superoxide anion (O(2)(-.)). In a similar way, whole diaphragmatic muscle and diaphragm mitochondria from endotoxemic rats showed a progressive increase in H(2)O(2) production associated with uncoupling and decreased phosphorylating capacity. Simultaneous with the maximal impairment in respiration (6 h after LPS), nitration of mitochondrial proteins (a peroxynitrite footprint) was detected and diaphragmatic force was reduced. Functional mitochondrial abnormalities, nitration of mitochondrial proteins, and the decrease in force were significantly attenuated by administration of the NOS inhibitor L-NMMA. These results show that increased and sustained NO levels lead to a consecutive formation of O(2)(-.) that reacts with NO to form peroxynitrite, which in turn impairs mitochondrial function, which probably contributes to the impairment of muscle contractility. during endotoxemia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0892-6638
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1637-46
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10463956-Animals, pubmed-meshheading:10463956-Diaphragm, pubmed-meshheading:10463956-Endotoxemia, pubmed-meshheading:10463956-Escherichia coli, pubmed-meshheading:10463956-Hydrogen Peroxide, pubmed-meshheading:10463956-Kinetics, pubmed-meshheading:10463956-Lipopolysaccharides, pubmed-meshheading:10463956-Male, pubmed-meshheading:10463956-Mitochondria, Muscle, pubmed-meshheading:10463956-Muscle Contraction, pubmed-meshheading:10463956-Nitrates, pubmed-meshheading:10463956-Nitric Oxide, pubmed-meshheading:10463956-Nitric Oxide Synthase, pubmed-meshheading:10463956-Nitric Oxide Synthase Type II, pubmed-meshheading:10463956-Oxygen Consumption, pubmed-meshheading:10463956-Rats, pubmed-meshheading:10463956-Rats, Sprague-Dawley, pubmed-meshheading:10463956-Superoxide Dismutase, pubmed-meshheading:10463956-Superoxides, pubmed-meshheading:10463956-omega-N-Methylarginine
pubmed:year
1999
pubmed:articleTitle
Endogenous peroxynitrite mediates mitochondrial dysfunction in rat diaphragm during endotoxemia.
pubmed:affiliation
Institut National de la Santé et de la Recherche Médicale (INSERM) U408 and IFR 02, Faculté X. Bichat, Paris, France. jbb2@bichat.inserm.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't