Morphine reverses the effects of 1-methyl-4-phenylpyridinium in PC12 cells through activating PI3K/Akt.
Morphine reverses the effects of 1-methyl-4-phenylpyridinium in PC12 cells through activating PI3K/Akt.
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吗啡通过激活 PI3K/Akt 逆转 1-甲基-4-苯基吡啶鎓对 PC12 细胞的影响。
DOI：
10.1080/00207454.2018.1492575
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发表时间：
2018
影响因子：
2.2
通讯作者：
Bai Jie
中科院分区：
文献类型：
--
作者：
Fan Yuan;Chen Yan;Zhang Se;Huang Mengbing;Wang Shengdong;Li Ye;Bai Jie
研究目的：帕金森病（PD）是一种神经退行性疾病。它是由黑质背侧部（substantia nigra pars rectuata，SNpc）多巴胺能神经元变性和多巴胺（dopamine，DA）缺失引起的。吗啡提高中脑边缘多巴胺系统中的多巴胺水平，并在缓解PD症状中发挥作用。然而，其分子机制尚不清楚。材料与方法：采用MTT比色法测定PC 12细胞活力。Western Blot检测酪氨酸羟化酶（TH）、硫氧还蛋白-1（Trx-1）、细胞周期蛋白D1（CyclinD 1）和细胞周期蛋白依赖性激酶5（Cdk 5）的表达。1-甲基-4-苯基吡啶（MPP+）可降低细胞活力和TH表达，吗啡可逆转MPP+的作用。MPP+使Trx-1、CyclinD 1、Cdk 5表达降低，吗啡可使其恢复。结论：吗啡通过激活磷脂酰肌醇-3-激酶（PI 3 K）/Akt通路，逆转MPP+诱导的Trx-1、CyclinD 1和Cdk 5表达的抑制作用。
Aim of the study:Parkinson’s disease (PD) is a neurodegenerative disorder. It is caused by the degeneration of dopaminergic neurons and the dopamine (DA) deletion in the substantia nigra pars compacta (SNpc). Morphine elevates the level of dopamine in the mesolimbic dopamine system and plays a role in alleviating PD symptoms. However, the molecular mechanism is still unclear. The aim of the study is to investigate the mechanism on morphine alleviating PD symptoms.Materials and methods:The viability of PC12 cells was measured by using MTT assay. The expressions of tyrosine hydroxylase (TH), thioredoxin-1 (Trx-1), CyclinD1 and Cyclin-dependent kinase5 (Cdk5) were detected by Western Blot.Results:In present study, we found that morphine increased the cell viability in PC12 cells. 1-methyl-4-phenylpyridi-nium (MPP+) reduced the cell viability and TH expression, which were reversed by morphine. MPP+ decreased the expressions of Trx-1, CyclinD1, Cdk5, which were restored by morphine. Moreover, the role of morphine in restoring the expressions of Trx-1, CyclinD1 and Cdk5 decreased by MPP+ was abolished by LY294002, phosphatidylinositol-3-kinase (PI3K)/Akt inhibitor.Conclusions:These results suggest that morphine reverses effects induced by MPP þ through activating PI3K/Akt pathway.