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阿司匹林对BV-2小胶质细胞中铁转运和储存蛋白表达的影响。

Effects of aspirin on expression of iron transport and storage proteins in BV-2 microglial cells.

作者信息

Xu Yan Xin, Du Fang, Jiang Li Rong, Gong Jing, Zhou Yu-Fu, Luo Qian Qian, Qian Zhong Ming, Ke Ya

机构信息

Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, PR China.

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.

出版信息

Neurochem Int. 2015 Dec;91:72-7. doi: 10.1016/j.neuint.2015.10.014. Epub 2015 Oct 30.

Abstract

In the light of recent studies, we hypothesized that aspirin might have the functions to regulate the expression of iron transport proteins and then affect cellular iron levels. To test this hypothesis, we investigated the effects of aspirin on expression of iron uptake protein transferrin receptor 1 (TfR1), iron release protein ferroportin 1 (Fpn1) and iron storage protein ferritin using Western blot analysis and on tumor necrosis factor (TNF)-αlpha, interleukin (IL)-6, interleukin (IL)-10 and hepcidin using quantitative real-time PCR in BV-2 microglial cells treated with lipopolysaccharides (LPS). We found that aspirin significantly down-regulated TfR1, while also up-regulated Fpn1 and ferritin expressions in BV-2 microglial cells in vitro. We also showed that TfR1 and Fpn1 expressions were significantly higher, while ferritin contents, IL-6, TNF-alpha and hepcidin mRNA levels were lower in cells treated with aspirin plus LPS than those in cells treated with LPS only. We concluded that aspirin has a negative effect on cell iron contents under 'normal' conditions and could partly reverse LPS-induced-disruption in cell iron balance under in vitro inflammatory conditions. Our findings also suggested that hepcidin might play a dominant role in the control of TfR1 expression by aspirin in the cells treated with LPS.

摘要

鉴于最近的研究,我们推测阿司匹林可能具有调节铁转运蛋白表达的功能,进而影响细胞内铁水平。为了验证这一假设,我们利用蛋白质免疫印迹分析研究了阿司匹林对铁摄取蛋白转铁蛋白受体1(TfR1)、铁释放蛋白铁转运蛋白1(Fpn1)和铁储存蛋白铁蛋白表达的影响,并利用定量实时聚合酶链反应研究了阿司匹林对脂多糖(LPS)处理的BV-2小胶质细胞中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、白细胞介素(IL)-10和铁调素表达的影响。我们发现,阿司匹林在体外显著下调BV-2小胶质细胞中TfR1的表达,同时上调Fpn1和铁蛋白的表达。我们还发现,与仅用LPS处理的细胞相比,用阿司匹林加LPS处理的细胞中TfR1和Fpn1的表达显著更高,而铁蛋白含量、IL-6、TNF-α和铁调素mRNA水平更低。我们得出结论,在“正常”条件下,阿司匹林对细胞铁含量有负面影响,并且在体外炎症条件下可以部分逆转LPS诱导的细胞铁平衡破坏。我们的研究结果还表明,在LPS处理的细胞中,铁调素可能在阿司匹林对TfR1表达的调控中起主导作用。

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