The inhibitor of I kappa B alpha phosphorylation BAY 11-7082 prevents NMDA neurotoxicity in mouse hippocampal slices.
NF-kappaB is a nuclear transcription factor involved in the control of fundamental cellular functions including cell survival. Among the many target genes of this factor, both pro- and anti-apoptotic genes have been described. To evaluate the contribution of NF-kappaB activation to excitotoxic insult, we analysed the effect of IkappaBalpha (IkappaBalpha) phosphorylation blockade on glutamate-induced toxicity in adult mouse hippocampal slices. By using immunocytochemical and EMSA techniques, we found that (i) acute exposure of hippocampal slices to NMDA induced nuclear translocation of NF-kappaB, (ii) NMDA-mediated activation of NF-kappaB was prevented by BAY 11-7082, an inhibitor of IkappaBalpha phosphorylation and degradation, and (iii) BAY 11-7082-mediated inhibition of NF-kappaB activation was associated with neuroprotection.
Goffi
F
F
Division of Pharmacology, Department of Biomedical Sciences and Biotechnologies, Viale Europa, 11, 25123 Brescia, Italy.
Boroni
F
F
Benarese
M
M
Sarnico
I
I
Benetti
A
A
Spano
P F
PF
Pizzi
M
M
D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000072000:NF-KappaB Inhibitor alpha; D009570:Nitriles / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology*
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D020672:I-kappa B Proteins; C000606205:Nfkbia protein, mouse; D009570:Nitriles; D013450:Sulfones; D000072000:NF-KappaB Inhibitor alpha; D016202:N-Methylaspartate