Activating Transcription Factor 4 Modulates BDNF Release from Microglial Cells

Activating Transcription Factor 4 Modulates BDNF Release from Microglial Cells
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激活转录因子 4 调节小胶质细胞释放 BDNF

DOI:
10.1007/s12031-013-0126-1
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发表时间:
2014-02
影响因子:
3.1
通讯作者:
Yuan, Hongbin
Yuan, Hongbin
中科院分区:
医学4区
文献类型:
--
作者:
Ouyang, Qing;Liu, Fangting;Xiang, Zhenghua;Yuan, Hongbin

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病理性疼痛是许多疾病的常见症状。其机制尚不清楚。转录激活因子4(Activating transcription factor 4,ATF4)在细胞活化过程中起着重要作用。脑源性神经营养因子(BDNF)是致病性疼痛的重要分子。本研究旨在探讨ATF4在诱导小胶质细胞释放BDNF中的作用。本研究培养小鼠小胶质细胞。采用酶联免疫吸附法测定培养液中BDNF的含量。通过基因转染在小胶质细胞中过表达ATF4。流式细胞仪检测小胶质细胞凋亡情况。结果表明,小胶质细胞表达ATF 4和蛋白酶激活受体2(PAR 2)。BDNF在小胶质细胞的培养液中可检测到,其在ATF4过表达的小胶质细胞中显著增加。ATF4过表达的小胶质细胞显示出高频率的凋亡细胞,这可以通过暴露于培养物中的PAR2激动剂类胰蛋白酶来抑制。类胰蛋白酶处理过的过表达ATF4的小胶质细胞保持较高的BDNF分泌。我们的结论是,ATF4的激活可以增加BDNF从小胶质细胞的释放。
Pathogenic pain is a common sign of many diseases. The mechanism is unclear. Activating transcription factor 4 (ATF4) plays a critical role in cell activation. Brain-derived neurotrophic factor (BDNF) is an important molecule in pathogenic pain. This study aims to investigate the role of ATF4 in inducing BDNF release from microglial cells. In this study, mouse microglial cells were cultured. The levels of BDNF in the culture medium were determined by enzyme-linked immunosorbent assay. Overexpression of ATF4 in microglial cells was performed by gene transfection. The apoptosis of microglial cells was assessed by flow cytometry. The results showed that microglial cells expressed ATF4 and protease-activated receptor-2 (PAR2). BDNF was detectable in the culture medium of microglial cells, which was significantly increased in the ATF4-overexpressing microglial cells. The ATF4-overexpressing microglial cells showed a high frequency of apoptotic cells, which could be inhibited by exposure to the PAR2 agonist tryptase in the culture. The tryptase-treated ATF4-overexpressing microglial cells kept higher secretion of BDNF. We conclude that the activation of ATF4 can increase BDNF release from microglial cells.
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