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Calcium signal-initiated early activation of NF-κB in neurons is a neuroprotective event in response to kainic acid-induced excitotoxicity

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Abstract

We demonstrate that activation of nuclear factor κB (NF-κB) in neurons is neuroprotective in response to kainic acid (KA)-induced excitotoxicity. Combination of Western blotting, immunocytochemistry, and electrophoresis mobility shift assay showed that KA exposure induced a fast but transient nuclear translocation of the NF-κB p65 subunit and increased DNA-binding activity of NF-κB in primary cultured cortical neurons. The transient NF-κB activity was associated with upregulation of antiapoptotic Bcl-xL and XIAP gene products revealed by real-time PCR. Knockdown of p65 decreased neuronal viability and antiapoptotic gene expression. In addition, we showed that KA-stimulated DNA-binding activity of NF-κB was associated with reactive oxygen species and calcium signals, using AMPA/KA receptor antagonist, calcium chelator, and antioxidant. These results suggest that the fast and transient activation of NF-κB initiated by calcium signals is one of the important proximal events in response to KA-induced excitotoxicity, which has neuroprotective effect against KA-induced apoptosis.

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Abbreviations

AMPA:

α-aminomethylisoxazole-propionic acid

CTZ:

cyclothiazide

DTT:

dithiothreitol

EMSA:

electrophoretic mobility shift assay

KA:

kainic acid

MTT:

3(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide

NF-κB:

nuclear factor κB

PMSF:

phenylmethylsulfonyl fluoride

RNAi:

RNA interference

ROS:

reactive oxygen species

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, Beijing, 100191, PR China

    Shu-Yan Li, Yu-Hong Jia, Guo-Sheng Wu, Guo-Shun An, Ju-Hua Ni & Hong-Ti Jia

  2. Department of Biochemistry, Medical School of Chifeng College, Chi Feng, 024001, PR China

    Wen-Ge Sun

  3. Department of Biochemistry and Molecular Biology, Capital University of Medical Sciences, You An Men Xitoutiao 8, Beijing, 100054, PR China

    Hong-Ti Jia

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  1. Shu-Yan Li
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  2. Wen-Ge Sun
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Correspondence to Shu-Yan Li.

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Published in Russian in Biokhimiya, 2010, Vol. 75, No. 1, pp. 125–135.

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Li, SY., Sun, WG., Jia, YH. et al. Calcium signal-initiated early activation of NF-κB in neurons is a neuroprotective event in response to kainic acid-induced excitotoxicity. Biochemistry Moscow 75, 101–110 (2010). https://doi.org/10.1134/S000629791001013X

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  • DOI: https://doi.org/10.1134/S000629791001013X

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