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Dephosphorelation of Bad and upregulation of Bcl-2 in hippocampus of rats following limbic seizure induced by kainic acid injection into amygdaloid nucleus

Li Tianfu, Lu Chuanzhen, Xia Zuoli, Niu Jingzhong, Yang Mingfeng, Luo Yumin, Hong Zhen

Department of Neurology, Affiliated Hospital of Taishan Medical College. Taian 271000, Shandong, China；Department of Neurology, Huashan Hospital, Fudan University. Shanghai 200040, China

Abstract

The purpose of the present study was to explore the seizure-induced changes in Bad (Bcl-2-associated death protein), 14-3-3, phosphoBad, Bcl-2 and Bcl-XL expression in the rat model of focal limbic seizure. Unilateral intra-amygdaloid injection of kainic acid (KA) was made to induce seizure. Electroencephalogram (EEG) and regional cerebral flow (r-CBF) were monitored continuously. Diazepam (30 mg/kg) was administered to terminate the seizure. The apoptotic and surviving neurons in the hippocampus were observed by terminal deoxynucleotidyl transferrase-mediated dUTP nick end labeling (TUNEL) and cresyl violet staining, the expression of Bad, 14-3-3, phosphoBad, Bcl-2 and Bcl-XL were detected with immunofluoresence, Western blot and immunoprecipitation. The results showed that TUNEL-positive neurons appeared at 8 h and reached maximum at 24 h following seizure cessation within the ipsilateral CA3 subfield of the hippocampus. Seizure induced the dephosphorylation of Bad and the dissociation of Bad from its chaperone protein 14-3-3 and subsequent dimerization of Bad with Bcl-XL. The expression of phosphoBad decreased and Bcl-2 increased. There was little change in r-CBF after the seizure. These results suggest that seizure leads to a dephosphorylation of Bad and an upregulation of Bcl-2. Dephosphorylation of Bad may be injurious while the upregulation of Bcl-2 may be protective to the brain damage induced by seizures, but not related with r-CBF.

Key words: Kainic acid;;;;;;;;

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Citing This Article：

Li Tianfu, Lu Chuanzhen, Xia Zuoli, Niu Jingzhong, Yang Mingfeng, Luo Yumin, Hong Zhen. Dephosphorelation of Bad and upregulation of Bcl-2 in hippocampus of rats following limbic seizure induced by kainic acid injection into amygdaloid nucleus. Acta Physiol Sin 2005; 57 (3): (in Chinese with English abstract).