Oxidative stress has been implicated in several neurodegenerative diseases affecting both neuronal and glial cells. The aim of this study was to investigate the involvement of reactive oxygen species in glutamate-evoked activation of NF-κB in primary astrocytes. A prolonged exposure to glutamate (24 h) caused a depletion of intracellular glutathione that, in astroglial cells, has been considered a biochemical change typical of early astrocyte dysfunction, leading to cell alterations occurring in the gliosis. These effects were initiated by AMPA/KA receptor activation and almost completely blocked by anti-oxidants. Indeed, we provide evidence that the incubation of primary astrocytes with a hydrophilic derivative of tocopherol, such as IRFI 016, was useful to reduce glutamate-induced oxidative effects. This agent also reduced in a dose-dependent manner the nuclear translocation of both p50 and p65 subunits of NF-κB. Altogether, these data confirm that GSH content plays a pivotal role to determine oxidative response to glutamate injury in primary astrocyte cultures and that NF-κB pathway is involved in this response. Furthermore, the positive effects obtained by IRFI 016 to prevent nuclear translocation of NF- κB may suggest new pharmacological strategies for antioxidant therapy and neuroprotection.

Glutamate promotes NF-kappa B pathway in primary astrocytes: Protective effects of IRFI 016, a synthetic vitamin E analogue

CACCAMO, Daniela;MARINI, Herbert Ryan;ADAMO, Elena Bianca;SQUADRITO, Francesco;IENTILE, Riccardo
2005-01-01

Abstract

Oxidative stress has been implicated in several neurodegenerative diseases affecting both neuronal and glial cells. The aim of this study was to investigate the involvement of reactive oxygen species in glutamate-evoked activation of NF-κB in primary astrocytes. A prolonged exposure to glutamate (24 h) caused a depletion of intracellular glutathione that, in astroglial cells, has been considered a biochemical change typical of early astrocyte dysfunction, leading to cell alterations occurring in the gliosis. These effects were initiated by AMPA/KA receptor activation and almost completely blocked by anti-oxidants. Indeed, we provide evidence that the incubation of primary astrocytes with a hydrophilic derivative of tocopherol, such as IRFI 016, was useful to reduce glutamate-induced oxidative effects. This agent also reduced in a dose-dependent manner the nuclear translocation of both p50 and p65 subunits of NF-κB. Altogether, these data confirm that GSH content plays a pivotal role to determine oxidative response to glutamate injury in primary astrocyte cultures and that NF-κB pathway is involved in this response. Furthermore, the positive effects obtained by IRFI 016 to prevent nuclear translocation of NF- κB may suggest new pharmacological strategies for antioxidant therapy and neuroprotection.
2005
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/1890059
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact