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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

Shu-Yan Li1*, Wen-Ge Sun2, Yu-Hong Jia1, Guo-Sheng Wu1, Guo-Shun An1, Ju-Hua Ni1, and Hong-Ti Jia1,3

1Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Xue Yuan Road 38, Beijing 100191, PR China; fax: +86-010-8280-1434; E-mail: shuyanli@bjmu.edu.cn

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

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

* To whom correspondence should be addressed.

Received February 16, 2009; Revision received June 19, 2009
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.
KEY WORDS: NF-κB, kainic acid, ROS, calcium, AMPA/KA receptor, neuronal survival/death

DOI: 10.1134/S000629791001013X