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首页> 外文学位 >Neuroprotective effects of dopamine agonists in terminally differentiated SH-SY5Y neuroblastoma cells.
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Neuroprotective effects of dopamine agonists in terminally differentiated SH-SY5Y neuroblastoma cells.

机译：多巴胺激动剂在终末分化的SH-SY5Y神经母细胞瘤细胞中的神经保护作用。

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摘要

Recent studies have demonstrated that the D3 preferring agonist pramipexole (PPX) can prevent neurotoxicity produced by levo-dopa in mesencephalic cultures and by MPP+ in the neuroblastoma SH-SY5Y cell line. However, the neuroprotective effects of PPX were not dopamine receptor mediated in the undifferentiated SH-SY5Y cells. We characterized differentiation conditions for the SH-SY5Y neuroblastoma cell line, cells differentiated with RA and TPA exhibited the high levels of expression TH, D2R, D3R and DAT but low levels of VMAT. Characterization of the kinetics of [3H]DA uptake and [3H]MPP+ uptake to DAT in RA/TPA differentiated cells was similar to that of rat and mouse caudate-putamen synaptosomes. RA/TPA differentiated cells evidenced high sensitivity to the neurotoxic effects of MPP+ (LD50 of 100 muM), and the neurotoxic effects of MPP+ were blocked with the DAT inhibitor GBR12909. The neuroprotective effect of PPX was dose-dependent (EC50 = 41 mum) and was completely antagonized by D2-like antagonists spiperone and U99194A but not by the D1 antagonist SCH23390.; To test if D3 receptor preferring agonists S32504 and pramipexole act through D2 and/or D3 receptors, we utilized the RA/TPA differentiated SH-SY5Y cell line. The cytotoxic effects of MPP+ were antagonized only by S32504 (EC50 = 2.0 muM) and pramipexole (EC 50 = 64.3 muM) at all time points. Neuroprotection afforded by EC 50 doses of S32504 and pramipexole were antagonized by D3 antagonists; S33084, U99194A, SB269652, D2/D3 antagonist raclopride, and D2 antagonist LY741626. Raclopride and L741626 provided complete anatagonism and U99194A, S33084 and SB269652 produced nearly maximal antagonism; and the neuroprotection by pramipexole and S32504 was ineffectively antagonized by SCH23390, haloperidol and spiperone. Thus, S32504 and pramipexole partly act through D3 receptor to protect against MPP+-induced toxicity in terminally differentiated SH-SY5Y neurons.
机译：最近的研究表明，首选D3激动剂普拉克索（PPX）可以预防中脑培养物中左旋多巴和成神经细胞瘤SH-SY5Y细胞系中的MPP +产生的神经毒性。然而，PPX的神经保护作用不是未分化的SH-SY5Y细胞中介导的多巴胺受体。我们表征了SH-SY5Y神经母细胞瘤细胞系的分化条件，用RA和TPA分化的细胞表现出高水平的TH，D2R，D3R和DAT表达，但VMAT水平低。 RA / TPA分化的细胞中DAT吸收[3H] DA和[3H] MPP +吸收的动力学特性与大鼠和小鼠尾状-丘脑突触小体相似。 RA / TPA分化的细胞对MPP +的神经毒性作用（LD50为100μM）具有高度敏感性，并且DAT抑制剂GBR12909阻断了MPP +的神经毒性作用。 PPX的神经保护作用是剂量依赖性的（EC50 = 41毫米），并被D2样拮抗剂spiperone和U99194A完全拮抗，但不被D1拮抗剂SCH23390拮抗。为了测试优选激动剂S32504和普拉克索的D3受体是否通过D2和/或D3受体起作用，我们利用了RA / TPA分化的SH-SY5Y细胞系。在所有时间点，仅S32504（EC50 = 2.0μM）和普拉克索（EC 50 = 64.3μM）拮抗MPP +的细胞毒性作用。 EC 3剂量的S32504和普拉克索所提供的神经保护作用被D3拮抗剂拮抗。 S33084，U99194A，SB269652，D2 / D3拮抗剂雷洛必利和D2拮抗剂LY741626。 Raclopride和L741626提供了完全的拮抗作用，而U99194A，S33084和SB269652产生了最大的拮抗作用。 SCH23390，氟哌啶醇和哌啶酮对普拉克索和S32504的神经保护作用无效。因此，S32504和普拉克索部分地通过D3受体起作用，以保护MPP +诱导的终分化SH-SY5Y神经元毒性。

著录项

  • 作者

    Presgraves, Steven Preston.;

  • 作者单位

    Arizona State University.;

  • 授予单位 Arizona State University.;
  • 学科 Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2004
  • 页码 120 p.
  • 总页数 120
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经科学;
  • 关键词

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