PMID: 9422392Jan 9, 1998Paper

Pretreatment of astrocytes with interferon-alpha/beta prevents neuronal mitochondrial respiratory chain damage

Journal of Neurochemistry
V C StewartS J Heales

Abstract

Excessive nitric oxide/peroxynitrite generation has been implicated in the pathogenesis of multiple sclerosis, and the demonstration of increased astrocytic nitric oxide synthase activity in the postmortem brain of multiple sclerosis patients supports this hypothesis. Interferon-beta is used for the treatment of multiple sclerosis, but currently little is known regarding its mode of action. Exposure of astrocytes in culture to interferon-gamma plus lipopolysaccharide results in stimulation of nitric oxide release. Using a coculture system, we have been able to use astrocytes as a source of nitric oxide/peroxynitrite in an attempt to "model" the effects of raised cytokine levels observed in multiple sclerosis and to monitor the effect on neurones. Our results indicate that stimulation of astrocytic nitric oxide synthase activity causes significant damage to the mitochondrial activities of complexes II/III and IV of neighbouring neurones. This damage was prevented by a nitric oxide synthase inhibitor, suggesting that the damage was nitric oxide-mediated. Furthermore, interferon-alpha/beta also prevented this damage. In view of these results, we suggest that a possible mechanism of action of interferon-beta in the treatment of mul...Continue Reading

Citations

Feb 16, 1999·Brain Pathology·K J SmithP A Felts
Feb 15, 2000·Annals of the New York Academy of Sciences·R StoneS J Heales
May 20, 2017·Neurochemical Research·Yoshiki Koriyama, Ayako Furukawa
Jun 15, 2006·Antioxidants & Redox Signaling·Joann M Gensert, Rajiv R Ratan
Jun 15, 2006·Antioxidants & Redox Signaling·Juan P Bolaños, Angeles Almeida
Oct 1, 2010·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Marcelo R Vargas, Jeffrey A Johnson
Mar 6, 2002·The European Journal of Neuroscience·V C StewartS J R Heales
Oct 22, 2008·The International Journal of Neuroscience·Münire Kilinç ToprakMuhtesem Ağildere
Oct 17, 2009·Nanotechnology·Daniele VergaraRoss Rinaldi
Sep 24, 2008·Journal of Neurochemistry·Lynsey G BilslandMichael R Duchen
Oct 3, 2012·Journal of the Neurological Sciences·Ivana StojanovicMaja Stukalov
May 13, 1999·Biochimica Et Biophysica Acta·G C Brown
Jan 25, 2003·Free Radical Biology & Medicine·Victoria C Stewart, Simon J R Heales

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