Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-10-29
pubmed:abstractText
Nitric oxide (NO) is hypothesized to play a role in the immunopathogenesis of multiple sclerosis (MS). Increased levels of NO metabolites have been found in patients with MS. Peroxynitrite, generated by the reaction of NO with superoxide at sites of inflammation, is a strong oxidant capable of damaging tissues and cells. Inducible NO synthase (iNOS) is up-regulated in the CNS of animals with experimental allergic encephalomyelitis (EAE) and in patients with MS. In this study, Western blots of cerebrospinal fluid (CSF) from patients with MS demonstrated the presence of iNOS, which was absent in CSF from control subjects. There was also NOS activity present in both MS and control CSF. Total NOS activity was increased (by 24%) in the CSF from MS patients compared with matched controls. The addition of 0.1 mM ITU (a specific iNOS inhibitor) to the samples did not change the activity of the control samples but decreased the NOS activity in the MS samples to almost control levels. The addition of 1 mM L-NMMA (a nonisoform specific NOS inhibitor), completely inhibited NOS activity in CSF from control and MS subjects. Nitrotyrosine immunostaining of CSF proteins was detectable in controls but was greatly increased in MS samples. There were also significant increases in CSF nitrate + nitrite and oxidant-enhanced luminescence in MS samples compared with controls. Additionally, a significant decrease in reduced glutathione and significant increases in oxidized glutathione and S-nitrosothiols were found in MS samples compared with controls. Parallel changes in NO metabolites were observed in the plasma of MS patients, compared with controls, and accompanied a significant increase of reduced glutathione. These data strongly support a role for nitrosative stress in the pathogenesis of MS and indicate that therapeutic strategies focussed on decreasing production of NO by iNOS and/or scavenging peroxynitrite may be useful in alleviating the neurological impairments that occur during MS relapse.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/3-nitrotyrosine, http://linkedlifedata.com/resource/pubmed/chemical/Catalase, http://linkedlifedata.com/resource/pubmed/chemical/Cerebrospinal Fluid Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Disulfide, http://linkedlifedata.com/resource/pubmed/chemical/NOS2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nitrates, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II, http://linkedlifedata.com/resource/pubmed/chemical/Nitrites, http://linkedlifedata.com/resource/pubmed/chemical/Peroxynitrous Acid, http://linkedlifedata.com/resource/pubmed/chemical/S-Nitrosothiols, http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0360-4012
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
580-7
pubmed:dateRevised
2011-10-27
pubmed:meshHeading
pubmed-meshheading:12404512-Adult, pubmed-meshheading:12404512-Blotting, Western, pubmed-meshheading:12404512-Catalase, pubmed-meshheading:12404512-Cerebrospinal Fluid Proteins, pubmed-meshheading:12404512-Female, pubmed-meshheading:12404512-Glutathione, pubmed-meshheading:12404512-Glutathione Disulfide, pubmed-meshheading:12404512-Humans, pubmed-meshheading:12404512-Male, pubmed-meshheading:12404512-Middle Aged, pubmed-meshheading:12404512-Multiple Sclerosis, pubmed-meshheading:12404512-Nitrates, pubmed-meshheading:12404512-Nitric Oxide Synthase, pubmed-meshheading:12404512-Nitric Oxide Synthase Type II, pubmed-meshheading:12404512-Nitrites, pubmed-meshheading:12404512-Peroxynitrous Acid, pubmed-meshheading:12404512-Recurrence, pubmed-meshheading:12404512-Reference Values, pubmed-meshheading:12404512-S-Nitrosothiols, pubmed-meshheading:12404512-Tyrosine
pubmed:year
2002
pubmed:articleTitle
Nitric oxide synthase is present in the cerebrospinal fluid of patients with active multiple sclerosis and is associated with increases in cerebrospinal fluid protein nitrotyrosine and S-nitrosothiols and with changes in glutathione levels.
pubmed:affiliation
Biochemistry and Molecular Biology Section, Department of Chemistry, Faculty of Medicine, University of Catania, Catania, Italy.
pubmed:publicationType
Journal Article, Clinical Trial, Controlled Clinical Trial, Research Support, Non-U.S. Gov't