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首页> 外文期刊>The European Journal of Neuroscience >Glutamate activates NF-kappaB through calpain in neurons.
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Glutamate activates NF-kappaB through calpain in neurons.

机译：谷氨酸通过神经元中的钙蛋白酶激活NF-κB。

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摘要

Glutamate induces gene transcription in numerous physiological and pathological conditions. Among the glutamate-responsive transcription factors, NF-kappaB has been mainly implicated in neuronal survival and death. Recent data also suggest a role of NF-kappaB in neural development and memory formation. In non-neuronal cells, degradation of the inhibitor IkappaBalpha represents a key step in NF-kappaB activation. However, little is known of how glutamate activates NF-kappaB in neurons. To investigate the signalling cascade involved we used primary murine cerebellar granule cells. Glutamate induced a rapid reduction of IkappaBalpha levels and nuclear translocation of the NF-kappaB subunit p65. The glutamate-induced reduction of IkappaBalpha levels was blocked by the N-methyl-d-aspartate inhibitor MK801. Specific inhibitors of the proteasome, caspase 3, and the phosphoinositide 3-kinase had no effect on glutamate-induced IkappaBalpha degradation. However, inhibition of the glutamate-activated Ca2+-dependent protease calpain by calpeptin completely blocked IkappaBalpha degradation and reduced the nuclear translocation of p65. Calpeptin also partially blocked glutamate-induced cell death. Our data indicate that the Ca2+-dependent protease calpain is involved in the NF-kappaB activation in neurons in response to N-methyl-d-aspartate receptor occupancy by glutamate. NF-kappaB activation by calpain may mediate the long-term effects of glutamate on neuron survival or memory formation.
机译：谷氨酸在许多生理和病理条件下诱导基因转录。在谷氨酸应答的转录因子中，NF-κB主要与神经元的存活和死亡有关。最近的数据还表明NF-κB在神经发育和记忆形成中的作用。在非神经元细胞中，抑制剂IkappaBalpha的降解代表了NF-kappaB激活的关键步骤。然而，关于谷氨酸如何激活神经元中的NF-κB知之甚少。为了研究涉及的信号传导级联，我们使用了原代鼠小脑颗粒细胞。谷氨酸诱导了IkappaBalpha水平的快速降低和NF-kappaB亚基p65的核易位。谷氨酸诱导的IkappaBalpha水平降低被N-甲基-d-天冬氨酸抑制剂MK801阻断。蛋白酶体，caspase 3和磷酸肌醇3激酶的特定抑制剂对谷氨酸诱导的IkappaBalpha降解没有影响。但是，钙蛋白酶抑制谷氨酸激活的Ca2 +依赖性蛋白酶钙蛋白酶可以完全阻断IkappaBalpha降解并减少p65的核易位。钙蛋白酶肽还部分阻止谷氨酸诱导的细胞死亡。我们的数据表明，Ca2 +依赖性蛋白酶钙蛋白酶参与了神经元对谷氨酸的N-甲基-d-天冬氨酸受体占据的响应中的NF-κB活化。钙蛋白酶激活NF-κB可能介导谷氨酸对神经元存活或记忆形成的长期影响。

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