The proapoptotic member of the Bcl‐2 family Bcl‐2 / E1B‐19K‐interacting protein 3 is a mediator of caspase‐independent neuronal death in excitotoxicity
The proapoptotic member of the Bcl‐2 family Bcl‐2 / E1B‐19K‐interacting protein 3 is a mediator of caspase‐independent neuronal death in excitotoxicity
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DOI：
10.1111/j.1742-4658.2010.07939.x
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发表时间：
2011-01
期刊：
影响因子：
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通讯作者：
Zhengfeng Zhang;Ruoyang Shi;Jiequn Weng;Xingshun Xu;Xin-min Li;T. Gao;J. Kong
中科院分区：
文献类型：
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作者：
Zhengfeng Zhang;Ruoyang Shi;Jiequn Weng;Xingshun Xu;Xin-min Li;T. Gao;J. Kong
已证明非半胱天冬酶依赖性神经元死亡发生在神经兴奋性毒性中。在这里，我们测试了编码Bcl-2/E1 B-19 K相互作用蛋白3（BNIP 3）的基因介导兴奋性毒性中的caspase非依赖性神经元死亡的假设。在正常情况下，BNIP 3在神经元中检测不到。在兴奋性毒性的体内和体外模型中，BNIP 3表达在神经元中显著增加。原代海马神经元中全长BNIP 3的表达诱导非典型细胞死亡，这需要蛋白质合成，但在很大程度上不依赖于caspase活性。通过RNA干扰抑制BNIP 3表达可防止谷氨酸诱导的神经元细胞死亡。因此，BNIP 3的激活和表达似乎是必要的和足够的兴奋性毒性神经元凋亡。这些结果表明，BNIP 3可能是神经元拯救策略的新靶点。
Caspase‐independent neuronal death has been shown to occur in neuroexcitotoxicity. Here, we tested the hypothesis that the gene encoding Bcl‐2/E1B‐19K‐interacting protein 3 (BNIP3) mediates caspase‐independent neuronal death in excitotoxicity. BNIP3 was not detectable in neurons under normal condition. BNIP3 expression was increased dramatically in neurons in both in vivo and in vitro models of excitotoxicity. Expression of full‐length BNIP3 in primary hippocampal neurons induced atypical cell death that required protein synthesis but was largely independent of caspase activities. Inhibition of BNIP3 expression by RNA interference protected against glutamate‐induced neuronal cell death. Thus, BNIP3 activation and expression appears to be both necessary and sufficient for neuronal apoptosis in excitotoxicity. These results suggest that BNIP3 may be a new target for neuronal rescue strategies.