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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Expression of the activating transcription factor 3 prevents c-Jun N-terminal kinase-induced neuronal death by promoting heat shock protein 27 expression and Akt activation.
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Expression of the activating transcription factor 3 prevents c-Jun N-terminal kinase-induced neuronal death by promoting heat shock protein 27 expression and Akt activation.

机译:活化转录因子3的表达通过促进热休克蛋白27的表达和Akt活化来防止c-Jun N末端激酶诱导的神经元死亡。

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摘要

Activating transcription factor 3 (ATF3) is induced and functions both as a cellular response to stress and to stimulate proliferation in multiple tissues. However, in the nervous system ATF3 is expressed only in injured neurons. Here we reveal a function of ATF3 in neurons under death stress. Overexpression of ATF3 by adenovirus inhibits the mitogen-activated kinase kinase kinase 1 (MEKK1)-c-Jun N-Terminal Kinase (JNK)-induced apoptosis and induces neurite elongation via Akt activation in PC12 cells and superior nerve ganglion neurons. A DNA microarray study reveals that ATF3 expression and JNK activation induce expression of the heat shock protein 27 (Hsp27). Immunoprecipitation analysis and promoter assay for Hsp27 expression suggest that both ATF3 and c-Jun are necessary for transcriptional activation of Hsp27. Hsp27 expression significantly inhibits JNK-induced apoptosis as well as Akt activation in PC12 cells and superior cervical ganglion neurons. We conclude that the combination of ATF3 and c-Jun induces the anti-apoptotic factor Hsp27, which directly or indirectly activates Akt, and thereby possibly inhibits apoptosis and induces nerve elongation. Our results suggest that ATF3- and c-Jun-induced Hsp27 expression is a novel survival response in neurons under death stress such as nerve injury.
机译:激活转录因子3(ATF3)被诱导,既可以作为细胞对应激的反应,又可以刺激多种组织的增殖。但是,在神经系统中,ATF3仅在受损的神经元中表达。在这里,我们揭示了在死亡压力下神经元中ATF3的功能。腺病毒过量表达ATF3会抑制丝裂原活化的激酶激酶激酶1(MEKK1)-c-Jun N末端激酶(JNK)诱导的凋亡,并通过PC12细胞和上神经节神经元神经元的Akt激活诱导神经突伸长。 DNA微阵列研究表明,ATF3表达和JNK激活诱导了热激蛋白27(Hsp27)的表达。 Hsp27表达的免疫沉淀分析和启动子测定表明,ATF3和c-Jun都是Hsp27转录激活所必需的。 Hsp27表达显着抑制PC12细胞和上颈神经节神经元中JNK诱导的凋亡以及Akt激活。我们得出的结论是,ATF3和c-Jun的组合可诱导抗凋亡因子Hsp27,后者直接或间接激活Akt,从而可能抑制细胞凋亡并诱导神经伸长。我们的结果表明,ATF3和c-Jun诱导的Hsp27表达是在死亡应激(例如神经损伤)下神经元中的新型存活反应。

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