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

Calabrese, Vittorio and Scapagnini, Giovanni and Ravagna, Agrippino and Bella, Rita and Foresti, Roberta and Bates, Timothy E. and Giuffrida Stella, Anna-Maria and Pennisi, Giovanni (2002) 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. Journal of Neuroscience Research, 70 (4). pp. 580-7. ISSN 0360-4012

Full text not available from this repository.

Item Type:Article
Item Status:Live Archive

Abstract

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.

Keywords:NO, NOS, Nitric oxide synthase, Nitric oxide, peroxynitrite, multiple sclerosis, nitrotyrosine, S-nitrosothiols, Glutathione
Subjects:B Subjects allied to Medicine > B131 Cellular Pathology
A Medicine and Dentistry > A100 Pre-clinical Medicine
B Subjects allied to Medicine > B140 Neuroscience
B Subjects allied to Medicine > B132 Pathobiology
A Medicine and Dentistry > A300 Clinical Medicine
B Subjects allied to Medicine > B130 Pathology
Divisions:College of Science > School of Life Sciences
Related URLs:
ID Code:5257
Deposited On:08 Jun 2013 12:43

Repository Staff Only: item control page