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首页> 外文期刊>Journal of psychopharmacology >Interferon-alpha-induced serotonin uptake in Jurkat T cells via mitogen-activated protein kinase and transcriptional regulation of the serotonin transporter.
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Interferon-alpha-induced serotonin uptake in Jurkat T cells via mitogen-activated protein kinase and transcriptional regulation of the serotonin transporter.

机译:干扰素α通过有丝分裂原激活的蛋白激酶和5-羟色胺转运蛋白的转录调控在Jurkat T细胞中吸收5-羟色胺。

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摘要

Interferon (IFN)-alpha upregulates serotonin (5-HT) uptake and serotonin transporter (5-HTT) messenger ribonucleic acid (mRNA) expression in immune cells, which implies the mechanism underlying IFN-alpha-induced depression. However, the signal transduction of this effect remains unclear. We investigated whether the effects of IFN-alpha on the functions of 5-HTT were related to mitogen-activated protein kinase (MAPK). By performing Western blotting, real-time reverse transcriptase-polymerase chain reaction and [3H]5-HT labelling, we examined MAPK phosphorylation, 5-HTT mRNA expression and 5-HT uptake in Jurkat T cells. The cells had been cultured for different time periods (1) with IFN-alpha alone and (2) preincubated with either MAPK inhibitors or with the selective serotonin reuptake inhibitor, fluoxetine, and subsequently cultured along with IFN-alpha. The levels of MAPK phosphorylation, 5-HTT mRNA expression and 5-HT uptake all increased in the IFN-alpha-treated cells but were blocked in those that were pretreated with MAPK inhibitors and fluoxetine. These results appear to clarify the association of depression with IFN-alpha-induced 5-HT uptake that reduces the 5-HT levels and IFN-alpha-regulated transcription of 5-HTT; further, the results suggest the involvement of MAPK in this process.
机译:干扰素(IFN)-α上调免疫细胞中5-羟色胺(5-HT)的摄取和5-羟色胺转运蛋白(5-HTT)信使核糖核酸(mRNA)的表达,这暗示了IFN-α诱导的抑郁症的潜在机制。但是,这种作用的信号转导仍不清楚。我们调查了IFN-α对5-HTT功能的影响是否与有丝分裂原激活的蛋白激酶(MAPK)相关。通过执行蛋白质印迹,实时逆转录聚合酶链反应和[3H] 5-HT标记,我们检查了Jurkat T细胞中的MAPK磷酸化,5-HTT mRNA表达和5-HT摄取。将细胞培养了不同的时间段(1)仅使用IFN-α,并且(2)与MAPK抑制剂或选择性5-羟色胺再摄取抑制剂氟西汀预孵育,然后与IFN-α一起培养。 MAPK磷酸化,5-HTT mRNA表达和5-HT摄取水平在IFN-α处理的细胞中均增加,但在用MAPK抑制剂和氟西汀预处理的细胞中被阻断。这些结果似乎澄清了抑郁症与IFN-α诱导的5-HT摄取的相关性,后者降低了5-HT的水平和IFN-α调节的5-HTT转录。进一步地,结果表明MAPK参与了该过程。

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