G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury.
G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury.
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DOI：
10.1177/1744806916682242
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Tao YX
中科院分区：
文献类型：
--
作者：
Liang L;Zhao JY;Gu X;Wu S;Mo K;Xiong M;Marie Lutz B;Bekker A;Tao YX
神经病理性疼痛是一种令人痛苦和衰弱的疾病，临床上仍然管理不善。阿片类药物，如吗啡，仍然是治疗这种疾病的主要处方药物，但其镇痛效果非常不令人满意，部分原因是神经损伤诱导的背根神经节的一级感觉神经元中阿片受体的减少。G9a是基因表达的阻遏物。我们发现，神经损伤诱导的G9a及其催化的抑制性标记物H3K9m2的增加负责Oprm1，Oprk1和Oprd1基因在受伤的背根神经节的表观遗传沉默。阻断这些增加拯救背根神经节Oprm1，Oprk1和Oprd1基因表达和吗啡或洛哌丁胺镇痛，并防止神经病理性疼痛条件下吗啡或洛哌丁胺诱导的镇痛耐受的发展。相反，模仿这些增加减少了三种阿片受体的表达，并促进了初级传入神经递质的μ阿片受体门控释放。从机制上讲，神经损伤诱导的G9a和H3K9me2与Oprm1基因结合活性的增加与环AMP反应元件结合蛋白与Oprm1基因的结合减少有关。这些研究结果表明，G9 a参与了神经损伤诱导的Oprm 1基因减少，这可能是通过G9 a触发的环AMP反应元件结合蛋白与该基因的接触的阻断来实现的。
Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of dorsal root ganglia. G9a is a repressor of gene expression. We found that nerve injury-induced increases in G9a and its catalyzed repressive marker H3K9m2 are responsible for epigenetic silencing of Oprm1, Oprk1, and Oprd1 genes in the injured dorsal root ganglia. Blocking these increases rescued dorsal root ganglia Oprm1, Oprk1, and Oprd1 gene expression and morphine or loperamide analgesia and prevented the development of morphine or loperamide-induced analgesic tolerance under neuropathic pain conditions. Conversely, mimicking these increases reduced the expression of three opioid receptors and promoted the mu opioid receptor-gated release of primary afferent neurotransmitters. Mechanistically, nerve injury-induced increases in the binding activity of G9a and H3K9me2 to the Oprm1 gene were associated with the reduced binding of cyclic AMP response element binding protein to the Oprm1 gene. These findings suggest that G9a participates in the nerve injury-induced reduction of the Oprm1 gene likely through G9a-triggered blockage in the access of cyclic AMP response element binding protein to this gene.
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影响因子：
4
作者：
Liang, Lingli;Fan, Longchang;Tao, Bo;Yaster, Myron;Tao, Yuan-Xiang
通讯作者：
Tao, Yuan-Xiang
影响因子：
7.4
作者：
Obara, Ilona;Parkitna, Jan Rodriguez;Przewlocki, Ryszard
通讯作者：
Przewlocki, Ryszard
影响因子：
7.4
作者：
Guan, Yun;Johanek, Lisa M.;Raja, Srinivasa N.
通讯作者：
Raja, Srinivasa N.
影响因子：
10.5
作者：
Esteve, Pierre-Olivier;Chin, Hang Gyeong;Pradhan, Sriharsa
通讯作者：
Pradhan, Sriharsa
DOI：
10.1523/jneurosci.1357-12.2012
发表时间：
2012-11-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Sun H;Maze I;Dietz DM;Scobie KN;Kennedy PJ;Damez-Werno D;Neve RL;Zachariou V;Shen L;Nestler EJ
通讯作者：
Nestler EJ