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脂多糖和出血对参与铁和血红素转运的肠道蛋白表达的影响。

Effect of lipopolysaccharide and bleeding on the expression of intestinal proteins involved in iron and haem transport.

作者信息

Krijt J, Vokurka M, Sefc L, Duricová D, Necas E

机构信息

Institute of Pathophysiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.

出版信息

Folia Biol (Praha). 2006;52(1-2):1-5.

PMID:17007103
Abstract

Haem carrier protein 1 (Hcpl) is a component of the haem-iron uptake pathway in the small intestine. Using quantitative real-time PCR, we examined the expression of Hcp1 and other intestinal iron-transporting proteins in male C57BL/6 mice with experimentally altered iron homeostasis. Intestinal Hcp1 mRNA content was not significantly changed by iron overload (600 mg/kg); however, it was increased to 170 % of controls 72 h after withdrawal of 0.7 ml of blood; the same treatment increased intestinal Cybrd1 mRNA to 900 % of controls. LPS treatment (1 mg/kg, 6 h) decreased intestinal Hcp1 mRNA content to 66 % of controls and Flvcr mRNA content to 65 % of controls, while Cybrd1 mRNA, Dmt1 mRNA and Fpn1 mRNA decreased to 6 %, 43 % and 32 %, respectively. In 129SvJ mice with targeted disruption of the hemojuvelin (Hfe2) gene, which display very low expression of liver hepcidin, Cybrd1 mRNA content increased to 1040 %, Dmt1 mRNA content to 200 % and Fpn1 mRNA to 150 % when compared to wild-type mice; changes in Hcp1, Abcg2 and Flver mRNA content were only minor. Overall, these results suggest that, during inflammation, the intestinal haem-iron uptake pathway is not as strongly transcriptionally downregulated as the non-haem iron uptake pathway. A decrease in circulating hepcidin increases the expression of proteins participating in non-haem iron uptake, but has no significant effect on Hcp1 mRNA content.

摘要

血红素载体蛋白1(Hcpl)是小肠中血红素铁摄取途径的一个组成部分。我们使用定量实时PCR检测了铁稳态发生实验性改变的雄性C57BL/6小鼠中Hcp1及其他肠道铁转运蛋白的表达。铁过载(600mg/kg)对肠道Hcp1 mRNA含量无显著影响;然而,在抽取0.7ml血液72小时后,其含量增加至对照组的170%;相同处理使肠道Cybrd1 mRNA增加至对照组的900%。脂多糖处理(1mg/kg,6小时)使肠道Hcp1 mRNA含量降至对照组的66%,Flvcr mRNA含量降至对照组的65%,而Cybrd1 mRNA、Dmt1 mRNA和Fpn1 mRNA分别降至6%、43%和32%。在血色素沉着症相关蛋白(Hfe2)基因靶向敲除的129SvJ小鼠中,其肝脏铁调素表达极低,与野生型小鼠相比,Cybrd1 mRNA含量增加至1040%,Dmt1 mRNA含量增加至200%,Fpn1 mRNA增加至150%;Hcp1、Abcg2和Flver mRNA含量变化较小。总体而言,这些结果表明,在炎症期间,肠道血红素铁摄取途径的转录下调程度不如非血红素铁摄取途径强烈。循环中铁调素的减少会增加参与非血红素铁摄取的蛋白质的表达,但对Hcp1 mRNA含量无显著影响。

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