High Constitutive NF-κB Activity Mediates Resistance to Oxidative Stress in Neuronal Cells
書誌事項
- 公開日
- 1998-05-01
- 権利情報
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- https://creativecommons.org/licenses/by-nc-sa/4.0/
- DOI
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- 10.1523/jneurosci.18-09-03224.1998
- 公開者
- Society for Neuroscience
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説明
<jats:p>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 β protein (Aβ) and hydrogen peroxide (H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>). Here, we show that the transcriptional activity and DNA binding activity of the redox-sensitive transcription factor NF-κB 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-κB in rCl8 cells with the synthetic glucocorticoid dexamethasone or by direct overexpression of a super-repressor mutant form of IκBα, a specific inhibitor of NF-κB, reversed the oxidative stress resistance phenotype of these cells and ultimately led to increased cell death after the challenge with H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>. Dexamethasone treatment also caused an increase in the protein level of IκBα. Our data show that an increased baseline of NF-κB 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-κB 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.</jats:p>
収録刊行物
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- The Journal of Neuroscience
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The Journal of Neuroscience 18 (9), 3224-3232, 1998-05-01
Society for Neuroscience