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Posttranscriptional regulation of neuronal nitric oxide synthase expression by IFN-gamma.

机译:转录后神经元一氧化氮合酶表达的调节。

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摘要

In this report, the mechanism through which interferon-gamma (IFN-gamma) regulates the expression of nitric oxide synthase (NOS-1) in neurons was examined. We have shown previously that IFN-gamma treatment of cells results in a two log inhibition of vesicular stomatitis virus (VSV) production. This inhibition of VSV replication is dependent both in vitro and in vivo on nitric oxide (NO) production by NOS-1. Furthermore, this effect is associated with the increased expression and activity of NOS-1 following IFN-gamma treatment. In vitro, exposure to IFN-gamma prior to infection with VSV is a prerequisite to establish an effective antiviral state, indicating the necessity for a priming event. Neuroblastoma cells (NB41A3) were treated with IFN-gamma or medium and examined for changes in NOS-1 protein and mRNA expression. NOS-1 protein expression was found to be increased after IFN-gamma treatment, and this was associated with increases in both neosynthesis and NOS-1 protein stability. NOS-1 transcription and mRNA levels were unaffected by IFN-gamma treatment. These data demonstrate that IFN-gamma regulates NOS-1 expression through posttranscriptional and posttranslational mechanisms.
机译:在此报告中,研究了干扰素-γ(IFN-γ)调节神经元中一氧化氮合酶(NOS-1)表达的机制。以前我们已经表明,IFN-γ处理细胞会导致水泡性口炎病毒(VSV)产生两个对数抑制。 VSV复制的这种抑制作用在体外和体内都依赖于NOS-1产生的一氧化氮(NO)。此外,这种作用与IFN-γ治疗后NOS-1的表达和活性增加有关。在体外,在感染VSV之前先接触IFN-γ是建立有效抗病毒状态的先决条件,这表明需要引发事件。神经母细胞瘤细胞(NB41A3)用IFN-γ或培养基处理,并检查NOS-1蛋白和mRNA表达的变化。发现在IFN-γ处理后NOS-1蛋白表达增加,这与新合成和NOS-1蛋白稳定性的增加有关。干扰素-γ处理不影响NOS-1转录和mRNA水平。这些数据表明,IFN-γ通过转录后和翻译后机制调节NOS-1的表达。

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