Seizure-like activity leads to the release of BAD from 14-3-3 protein and cell death in hippocampal neurons in vitro
Seizure-like activity leads to the release of BAD from 14-3-3 protein and cell death in hippocampal neurons in vitro
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DOI：
10.1038/sj.cdd.4401206
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发表时间：
2003-05-01
影响因子：
12.4
通讯作者：
Henshall, DC
中科院分区：
文献类型：
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作者：
Meller, R;Schindler, CK;Henshall, DC
癫痫诱发的神经元死亡可能涉及凋亡调节蛋白BCL-2家族的参与。在本研究中，我们检测了在慢性谷氨酸传递阻滞解除引起癫痫发作后，培养海马神经元中促凋亡BAD的激活。犬尿酸戒断引起癫痫样电活动的增加，这被AMPA （CNOX）和NMDA （MK801和AP5）受体功能阻滞剂抑制。然而，只有NMDA受体拮抗剂抑制钙进入，通过fura-2和海马神经元细胞死亡来评估。癫痫发作增加了细胞的caspase-3蛋白水解和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）。癫痫样活性诱导BAD去磷酸化并破坏其与14-3-3蛋白的结构相互作用。反过来，癫痫发作后BAD与抗凋亡BCL-XI二聚。然而，通路干预缺乏神经保护作用表明BAD可能在体外癫痫发作后的细胞死亡中起强化作用而不是促动作用。
Seizure-induced neuronal death may involve engagement of the BCL-2 family of apoptosis-regulating proteins. In the present study we examined the activation of proapoptotic BAD in cultured hippocampal neurons following seizures induced by removal of chronic glutamatergic transmission blockade. Kynurenic acid withdrawal elicited an increase in seizure-like electrical activity, which was inhibited by blockers of AMPA (CNOX) and NMDA (MK801 and AP5) receptor function. However, only NMDA receptor antagonists inhibited calcium entry as assessed by fura-2, and cell death of hippocampal neurons. Seizures increased proteolysis of caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) of cells. Seizure-like activity induced dephosphorylation of BAD and the disruption of its constitutive interaction with 14-3-3 proteins. In turn, BAD dimerized with antiapoptotic BCL-XI after seizures. However, the absence of neuroprotective effects of pathway intervention suggests that BAD may perform a reinforcement rather than instigator role in cell death following seizures in vitro.