Tian Jie, Gu Yang, Sun Ke, Wang Beilei, Chen Jie, Wang Xiangrui, Su Diansan
Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian road, Shanghai 200127, China.
Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian road, Shanghai 200127, China.
Brain Res. 2014 May 27;1565:1-7. doi: 10.1016/j.brainres.2014.04.007. Epub 2014 Apr 13.
[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 24-72h. 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 72h 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.
[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已显示出有前景的结果。然而，这种保护机制仍在研究中。当前的研究旨在检验DADLE可能调节神经元细胞转录的假说。用不同剂量的DADLE处理SH - SY5Y细胞和原代皮质神经元24 - 72小时。结果表明，在所检测的所有剂量和时间点，DADLE均显著抑制两种细胞中的细胞转录，且未造成细胞损伤。在原代神经元中去除DADLE恢复72小时后，转录活性完全恢复。δ阿片受体（DOR）不参与此过程，因为纳曲吲哚不能消除DADLE的转录抑制作用。在原代皮质神经元中的进一步研究表明，DADLE显著抑制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，这可能为其报道的神经保护作用提供机制性见解，并表明它作为神经保护的潜在治疗策略值得进一步探索。
