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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Shu-Yan Li^1*, Wen-Ge Sun², Yu-Hong Jia¹, Guo-Sheng Wu¹, Guo-Shun An¹, Ju-Hua Ni¹, and Hong-Ti Jia^1,3

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

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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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KEY WORDS: NF-κB, kainic acid, ROS, calcium, AMPA/KA receptor, neuronal survival/death

DOI: 10.1134/S000629791001013X

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