[d-Ala2, d-Leu5] encephalin (DADLE) reversibly inhibits cellular transcription in neurons without causing cell injury
[d-Ala2, d-Leu5] encephalin (DADLE) reversibly inhibits cellular transcription in neurons without causing cell injury
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DOI：
10.1016/j.brainres.2014.04.007
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发表时间：
2014-05
期刊：
影响因子：
2.9
通讯作者：
Jie Tian;Yang Gu;Keyang Sun;Beilei Wang;Jie Chen;Xiangrui Wang;D. Su
中科院分区：
文献类型：
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作者：
Jie Tian;Yang Gu;Keyang Sun;Beilei Wang;Jie Chen;Xiangrui Wang;D. Su
[d-丙氨酸(2)-d-亮氨酸(5)]-脑啡肽(DADLE)在保护神经元免受损伤方面显示出良好的效果。然而，这种保护的机制仍在调查中。目前的研究是为了验证DADLE可能调节神经元细胞转录的假设。用不同剂量的DADLE处理SH-SY5Y细胞和原代皮层神经元24-72小时，结果表明，在所有剂量和时间点，DADLE显著抑制两种细胞的细胞转录，而不引起细胞损伤。在没有DADLE的情况下，原代神经元恢复72小时后，转录活动完全恢复。Delta阿片受体不参与此过程，因为纳曲哚不能消除DADLE׳S的转录抑制作用。对原代皮质神经元的进一步研究表明，DADLE显著抑制了RNA聚合酶II C末端结构域(CTD)的Ser2和Ser5的磷酸化。这些数据表明，DADLE能够通过抑制神经元中RNA聚合酶II的磷酸化来降低细胞转录，这可能为了解其已报道的神经保护作用提供了机制上的见解，并表明DADLE作为一种潜在的神经保护治疗策略值得进一步探索。
[d-Ala(2)-d-Leu(5)]-Enkephalin (DADLE) has shown promising results in protecting neurons from damages. However, the mechanism for this protection is still under investigation. The current study was carried out to test the hypothesis that DADLE may regulate cellular transcription in neurons. SH-SY5Y cells and primary cortical neurons were treated with various doses of DADLE for 24–72 h. Results demonstrated that DADLE, at all doses and time points examined, significantly inhibited cellular transcription in both cells without causing cell injury. Following recovery for 72 h without DADLE in primary neurons, the transcriptional activity fully resumed. Delta opioid receptor (DOR) is not involved in this process, as Naltrindole could not abolish DADLE׳s transcriptional inhibitory effects. Further studies in primary cortical neurons show that DADLE significantly inhibited phosphorylation of Ser2 and Ser5 of the C-terminal domain (CTD) of RNA polymerase II. These data indicate that DADLE is able to decrease cellular transcription through inhibiting phosphorylation of RNA polymerase II in neurons, which may provide mechanistic insight into its reported neuroprotective effects, and suggests that it warrants further exploration as a potential therapeutic strategy for neuroprotection.