Increased oxidative stress brought on by pro-inflammatory cytokines in neurodegenerative processes and the protective role of nitrone-based free radical traps

Citation
Ra. Floyd et al., Increased oxidative stress brought on by pro-inflammatory cytokines in neurodegenerative processes and the protective role of nitrone-based free radical traps, LIFE SCI, 65(18-19), 1999, pp. 1893-1899
Citations number
18
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
LIFE SCIENCES
ISSN journal
0024-3205 → ACNP
Volume
65
Issue
18-19
Year of publication
1999
Pages
1893 - 1899
Database
ISI
SICI code
0024-3205(19991001)65:18-19<1893:IOSBOB>2.0.ZU;2-4
Abstract
Nitrone-based free radical traps (NFTs) have been shown to be protective in several neurodegenerative models. Our research has strongly implicated tha t: A) several neurodegenerative conditions exhibit increased levels of pro- inflammatory cytokines which consequently result in increased levels of oxi dative stress and B) that NFTs act in part by suppressing oxidative stress through suppression of the action of the cytokine cascade. Acquired Immune Deficiency Syndrome (AIDS) dementia complex (ADC) is one of several conditi ons where the data collected helped to develop these concepts. Novel observ ations include demonstration that IL-1 beta acts on cultured brain glia cel ls to invoke protein nitration and oxidative stress and that low levels of PBN (alpha-phenyl tert-butyl nitrone) inhibit this effect. We interpret the se data as indicating that PEN prevents IL-1 beta mediated peroxynitrite fo rmation. Additionally, we have found that the AIDS viral envelope protein g p120 upregulates mRNA for the cytokines TNF alpha and TNF beta in rat neona tal brain, and that PEN prevents this. Western blots of protein extracts sh owed upregulation of inducible nitric oxide synthase (iNOS) in gp120 treate d neonatal rat brains, and that PEN prevented induction of this enzyme as w ell. These observations underscore the general concept that PEN inhibits th e induction of genes which produce neurotoxic products, one of which is per oxynitrite formed by the reaction of nitric oxide with superoxide, and may act also by inhibiting the induction of cytokines which mediate pro-inflamm atory conditions in the brain.