Neuroprotective effects of pramipexole against tunicamycin-induced cell death in PC12 cells
Neuroprotective effects of pramipexole against tunicamycin-induced cell death in PC12 cells
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DOI：
10.1111/j.1440-1681.2009.05224.x
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发表时间：
2009-12-01
影响因子：
2.9
通讯作者：
Yoshizumi, Masanori
中科院分区：
文献类型：
--
作者：
Nakayama, Hitoshi;Zhao, Jing;Yoshizumi, Masanori
pripexole （PPX）是一种多巴胺D2和D3受体激动剂，通过多巴胺受体介导和非多巴胺能机制发挥神经保护作用。在本研究中，我们证明PPX降低了tunicamycin的毒性，tunicamycin是一种典型的内质网（ER）应激源，在PC12细胞的一个亚系PC12h中。用300 μ mol / L PPX在0.5 μ mol / L tunicamycin的作用下处理PC12h细胞24 h，采用3-（4,5-二甲基-2噻唑基）-2,5-二苯基-2 h -溴化四唑（MTT）和乳酸脱氢酶（LDH）释放法、Hoechst 33258染色和western blot分析PPX对tunicamycin诱导的细胞死亡的神经保护作用。Tunicamycin（0.2、0.3和0.5 μ g / mL）剂量依赖性地降低了PC12h细胞的MTT活性，增加了LDH释放。300 μ mol / L PPX处理可恢复tunicamycin诱导的细胞活力下降。多巴胺D2和D4受体拮抗剂Spiperone （10 μ mol / L）对PPX对tunicamycin的神经保护作用无影响。已知内质网应激和凋亡的标记蛋白被tunicamycin上调，但我们未检测到PPX对这些因子的显著影响。总之，我们推测ppx诱导的神经保护可能涉及几种机制的组合。
P>Pramipexole (PPX), a dopamine D2 and D3 receptor agonist, exerts neuroprotective effects via both dopamine receptor-mediated and non-dopaminergic mechanisms. In the present study, we demonstrate that PPX reduces the toxicity of tunicamycin, a typical endoplasmic reticulum (ER) stressor, in PC12h cells, a subline of PC12 cells.The PC12h cells were treated with 300 mu mol / L PPX in the presence of 0.5 mu mol / L tunicamycin for 24 h. The neuroprotective effects of PPX against tunicamycin-induced cell death were evaluated using 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays, Hoechst 33258 staining and western blot analysis.Tunicamycin (0.2, 0.3 and 0.5 mu g / mL) dose-dependently decreased MTT activity and increased LDH release from PC12h cells. Treatment with 300 mu mol / L PPX rescued the tunicamycin-induced decrease in cell viability.Spiperone (10 mu mol / L), a dopamine D2 and D4 receptor antagonist, had no effect on PPX neuroprotection against tunicamycin in these cells. Marker proteins of ER stress and apoptosis are known to be upregulated by tunicamycin, but we detected no significant effects of PPX on these factors.In conclusion, we speculate that a combination of several mechanisms may be involved in PPX-induced neuroprotection.