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Differential effects of hypoxia on untreated and NGF treated PC12 cells.

机译:缺氧对未经处理和经NGF处理的PC12细胞的差异作用。

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Perinatal hypoxia is known to induce long-lasting changes in the central dopaminergic system. In order to understand the cellular mechanism of these changes, we studied the effects of hypoxia on the levels of dopamine (DA) and tyrosine hydroxylase (TH) mRNA in untreated and NGF treated PC12 cells. On the second day after plating (DAP), cells were exposed to a hypoxic episode (pO2 = 10-20 mm Hg, 24 h), and the levels of DA and TH mRNA were examined on DAP 4 and DAP 8. In untreated cells, hypoxia induced a two fold increase both in DA and TH mRNA levels on DAP 4 which normalized up to DAP 8. This increase correlated with an activation of the hypoxia inducible factor (HIF-1alpha), measured with a reporter gene. In contrast, NGF treated cells responded to hypoxia with an increase of DA level on DAP 8. In these cells neither an increase of the HIF-1alpha activity measured immediately after hypoxia nor a significant increase of the TH mRNA level on DAP 8 were found. The findings indicate that NGF shifts the hypoxia induced changes of DA levels from a short-term to a long-term mode. The long-term increase of dopamine levels is the most likely result of changes connected with cell growth and differentiation and not the result of a long-term TH mRNA level increase.
机译:围产期缺氧会引起中枢多巴胺能系统的长期变化。为了了解这些变化的细胞机制,我们研究了缺氧对未经处理和经NGF处理的PC12细胞中多巴胺(DA)和酪氨酸羟化酶(TH)mRNA水平的影响。接种后第二天(DAP),将细胞暴露于低氧事件(pO2 = 10-20 mm Hg,24小时),并在DAP 4和DAP 8上检测DA和TH mRNA的水平。 ,低氧诱导DAP 4的DA和TH mRNA水平均增加了两倍,最高达到DAP 8的水平。这种增加与用报道基因测量的低氧诱导因子(HIF-1alpha)的激活有关。相反,NGF处理的细胞对缺氧有反应,DAP 8上的DA水平升高。在这些细胞中,既没有发现缺氧后立即测定的HIF-1alpha活性升高,也没有发现DAP 8上TH mRNA水平显着升高。研究结果表明,NGF将缺氧引起的DA水平改变从短期模式转变为长期模式。多巴胺水平的长期升高是与细胞生长和分化有关的变化的最可能结果,而不是长期TH mRNA水平升高的结果。

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