Activation of the Nuclear Factor-κB Is a Key Event in Brain Tolerance - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Neuroscience Année : 2001

Activation of the Nuclear Factor-κB Is a Key Event in Brain Tolerance

Résumé

The transcription factor nuclear factor-κB (NFκB) is an ubiquitously expressed inducible regulator of a broad range of genes and plays a pivotal role in cell death and survival pathways. Three models of brain tolerance (ischemic, epileptic, and polyunsaturated fatty acid-induced preconditioning), known to confer resistance to neurons against ischemia or status epilepticus, were used to determine whether NFκB mediated the late preconditioning. A sublethal 3 min ischemia, a dose of 5 mg/kg kainic acid (KA5) or 500 nmol of linolenic acid (LIN500) led to a rapid increase of NFκB DNA-binding activity and nuclear translocation of p65 and p50 subunits of NFκB in neurons. Pretreatment with the NFκB inhibitor diethyldithiocarbamate or κB decoy DNA blocked the increased DNA-binding activity and the nuclear translocation of NFκB and abolished the neuroprotective effects of different delayed preconditionings against severe ischemia or epilepsy. The inhibition of NFκB observed in rats preconditioned with 3 min ischemia, KA5 or LIN500 treatments compared with ischemic or epileptic controls was correlated with the prevention of the inducible degradation of the inhibitory protein IκBα. Preconditioning probably inhibits the activation of NFκB by interfering with a pathway that leads to the direct transcriptional activation of IκBα by NFκB itself. The present work provides evidence that activation of NFκB is a crucial step in the signal transduction pathway that underlies the development of brain tolerance and may open new strategies in the prevention of cerebral diseases, such as ischemia or epilepsy.
Fichier principal
Vignette du fichier
2001-JNeuro.PDF (741.9 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-02266280 , version 1 (13-08-2019)

Identifiants

Citer

Nicolas Blondeau, Catherine Widmann, Michel Lazdunski, Catherine Heurteaux. Activation of the Nuclear Factor-κB Is a Key Event in Brain Tolerance. Journal of Neuroscience, 2001, 21 (13), pp.4668-4677. ⟨10.1523/JNEUROSCI.21-13-04668.2001⟩. ⟨hal-02266280⟩
53 Consultations
47 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More