PMID: 9547231May 9, 1998Paper

High constitutive NF-kappaB activity mediates resistance to oxidative stress in neuronal cells

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
F Lezoualc'hC Behl

Abstract

Selected clones of the sympathetic precursor-like cell line PC12 (rCl8) are resistant to oxidative cell death induced by the Alzheimer's disease-associated amyloid beta protein (Abeta) and hydrogen peroxide (H2O2). Here, we show that the transcriptional activity and DNA binding activity of the redox-sensitive transcription factor NF-kappaB and its nuclear expression are constitutively increased in rCl8 cells compared with their nonresistant parental PC12 cell (PC12p) counterpart. Suppression of the transcriptional activity of NF-kappaB in rCl8 cells with the synthetic glucocorticoid dexamethasone or by direct overexpression of a super-repressor mutant form of IkappaBalpha, a specific inhibitor of NF-kappaB, reversed the oxidative stress resistance phenotype of these cells and ultimately led to increased cell death after the challenge with H2O2. Dexamethasone treatment also caused an increase in the protein level of IkappaBalpha. Our data show that an increased baseline of NF-kappaB activity may mediate the resistance of these cells of neuronal origin to oxidative stress. Therefore, the presented model may help to identify possible neuronal target genes of NF-kappaB and to further elucidate the molecular basis of the differentia...Continue Reading

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