Suppression of ribosomal protein synthesis and protein translation factors by Peg-interferon alpha/ribavirin in HCV patients blood mononuclear cells (PBMC).

Suppression of ribosomal protein synthesis and protein translation factors by Peg-interferon alpha/ribavirin in HCV patients blood mononuclear cells (PBMC).
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HCV患者血液单核细胞(PBMC)抑制核糖体蛋白合成和蛋白质翻译因子。

DOI:
10.1186/1479-5876-10-54
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发表时间:
2012-03-22
影响因子:
7.4
通讯作者:
Taylor MW
Taylor MW
中科院分区:
医学2区
文献类型:
--
作者:
Gupta R;Kim S;Taylor MW

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我们以前曾报道过许多干扰素刺激的基因(ISG)的诱导PBMC中收集的HCV感染患者在不同的时间开始干扰素-利巴韦林治疗后,使用DNA微阵列,以确定基因表达随时间的变化。在干扰素-利巴韦林治疗期间,几乎与上调的基因一样多的基因被下调(抑制)。通过不同的软件分析DNA微阵列,包括MAS 5(Affymetrix-Kegg)和GSEA(基因集富集分析)以鉴定上调和下调的特异性途径。数据是从一项临床试验中评估的,该试验是对68名患者的微阵列分析。上调的基因包括与NF-κ B、Toll样受体细胞因子-细胞因子相互作用以及补体和粘附途径相关的基因。最显著的下调途径是核糖体结构蛋白和真核翻译因子。核糖体蛋白基因的下调持续通过治疗直至最后一次测量,其在第28天。这种蛋白质合成装置的抑制可能解释干扰素-利巴韦林的长期副作用,并解释干扰素-利巴韦林对病毒蛋白质合成的非特异性作用。没有证据表明独特的转录因子或微小RNA参与。
We have previously reported the induction of many interferon stimulated genes (ISGs) in PBMC collected from patients infected with HCV at various times after initiation of interferon-ribavirin treatment using DNA microarrays to identify changes in gene expression with time. Almost as many genes are down regulated (suppressed) during interferon-ribavirin treatment as are up regulated. DNA microarrays were analyzed by different software, including MAS5 (Affymetrix-Kegg) and GSEA (gene set enrichment analysis) to identify specific pathways both up regulated and down regulated. Data was assessed from a clinical trial, which was a microarray analysis from 68 patients. Up regulated genes included genes associated with NF-kb, toll like receptor cytokine -cytokine interaction, and complement and adhesion pathways. The most prominent pathway down regulated was that for ribosomal structural proteins, and eukaryotic translational factors. Down regulation of ribosomal protein genes continued through the treatment up to the last measurement, which was at day 28. This suppression of the protein synthetic apparatus might explain the long-term side effects of interferon-ribavirin, and explain a non-specific effect of interferon-ribavirin on viral protein synthesis. There was no evidence for unique transcription factors or micro RNA involvement.
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影响因子: 7.7
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DOI: 10.1371/journal.pone.0000584
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