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PMID: 9547231 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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 ·Vol. 18 ·No. 9 ·1998-05-01 ·Pages 3224-32

Lezoualc'h F, Sagara Y, Holsboer F, Behl C

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 differential sensitivity of neurons in neurodegenerative conditions associated with an increased oxidative burden, such as in Alzheimer's disease.

MeSH Terms
Animals Calcium-Binding Proteins Cell Death/drug effects Cell Nucleus/metabolism Cytoplasm/metabolism DNA-Binding Proteins/metabolism Dexamethasone/pharmacology Glucocorticoids/pharmacology Hydrogen Peroxide/pharmacology I-kappa B Proteins Membrane Glycoproteins/biosynthesis NF-KappaB Inhibitor alpha NF-kappa B/antagonists & inhibitors,physiology Nerve Tissue Proteins/biosynthesis Neurons/physiology Oxidative Stress/physiology PC12 Cells Phenotype Rats Synaptotagmins Transcription, Genetic
Chemicals
Calcium-Binding Proteins DNA-Binding Proteins Glucocorticoids I-kappa B Proteins Membrane Glycoproteins NF-kappa B Nerve Tissue Proteins Nfkbia protein, rat Synaptotagmins NF-KappaB Inhibitor alpha Dexamethasone Hydrogen Peroxide
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lezoualc'h F
Max-Planck-Institute of Psychiatry, 80804 Munich, Germany.
Sagara Y
Holsboer F
Behl C
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1998-05-01
Pages
3224-32
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6792651
Subset
IM
Grants
NINDS NIH HHS · 1 F32 NS10032 · United States
External Links
PubMed source PMC Full Text View journal details
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