HIGH CONSTITUTIVE NF-KAPPA-B ACTIVITY MEDIATES RESISTANCE TO OXIDATIVE STRESS IN NEURONAL CELLS

Citation
F. Lezoualch et al., HIGH CONSTITUTIVE NF-KAPPA-B ACTIVITY MEDIATES RESISTANCE TO OXIDATIVE STRESS IN NEURONAL CELLS, The Journal of neuroscience, 18(9), 1998, pp. 3224-3232
Citations number
55
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
0270-6474
Volume
18
Issue
9
Year of publication
1998
Pages
3224 - 3232
Database
ISI
SICI code
0270-6474(1998)18:9<3224:HCNAMR>2.0.ZU;2-7
Abstract
Selected clones of the sympathetic precursor-like cell line PC12 (rCl8 ) are resistant to oxidative cell death induced by the Alzheimer's dis ease-associated amyloid beta protein (A beta) and hydrogen peroxide (H 2O2). Here, we show that the transcriptional activity and DNA binding activity of the redox-sensitive transcription factor NF-kappa B and it s nuclear expression are constitutively increased in rCl8 cells compar ed with their nonresistant parental PC12 cell (PC12p) counterpart. Sup pression of the transcriptional activity of NF-kappa B in rCl8 cells w ith the synthetic glucocorticoid dexamethasone or by direct overexpres sion of a super-repressor mutant form of I kappa B alpha, a specific i nhibitor of NF-kappa B, reversed the oxidative stress resistance pheno type of these cells and ultimately led to increased cell death after t he challenge with H2O2. Dexamethasone treatment also caused an increas e in the protein level of I kappa B alpha. Our data show that an incre ased baseline of NF-kappa B activity may mediate the resistance of the se cells of neuronal origin to oxidative stress. Therefore, the presen ted model may help to identify possible neuronal target genes of NF-ka ppa B and to further elucidate the molecular basis of the differential sensitivity of neurons in neurodegenerative conditions associated wit h an increased oxidative burden, such as in Alzheimer's disease.