Iron uptake from plasma transferrin by a transferrin receptor 2 mutant mouse model of haemochromatosis.
Iron uptake from plasma transferrin by a transferrin receptor 2 mutant mouse model of haemochromatosis.
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DOI：
10.1016/j.jhep.2009.12.010
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发表时间：
2010-03
影响因子：
25.7
通讯作者：
Trinder D
中科院分区：
文献类型：
--
作者：
Chua AC;Delima RD;Morgan EH;Herbison CE;Tirnitz-Parker JE;Graham RM;Fleming RE;Britton RS;Bacon BR;Olynyk JK;Trinder D
遗传性血色沉着症3型是由转铁蛋白受体(TFR)2基因突变引起的。TFR2已被证明在体外介导铁的转运和调节铁的动态平衡。这项研究的目的是利用Tfr2突变小鼠来确定Tfr2在体内铁转运中的作用。Tfr2突变型和野生型小鼠静脉注射~(59)Fe-转铁蛋白，测定组织对~(59)Fe的摄取。实时荧光定量聚合酶链式反应和Western印迹法检测Tfr1、Tfr2和铁蛋白的表达。免疫组织化学方法检测铁蛋白在细胞内的定位。与携带铁的野生型小鼠相比，Tfr2突变小鼠肝脏和脾的转铁蛋白结合铁摄取量分别降低了20%和65%，而十二指肠和肾脏的摄取量没有变化。在Tfr2突变小鼠中，肝脏Tfr2蛋白缺失，非实质细胞中铁转运蛋白蛋白表达增加，肝细胞中低水平表达。与铁负荷野生型小鼠相比，Tfr1的表达没有变化。与铁负荷野生型小鼠相比，Tfr2突变小鼠的脾Tfr2蛋白表达缺失，而Tfr1和铁蛋白表达增加。Tfr2突变小鼠肝脏转铁蛋白结合的铁摄取量略有下降，这表明Tfr2在肝脏铁转运中起着次要作用，其主要作用是调节铁代谢。Tfr2突变小鼠脾铁摄取受损可能是由于海普西丁mRNA水平降低而导致的铁门蛋白表达增加所致。
Hereditary haemochromatosis type 3 is caused by mutations in transferrin receptor (TFR) 2. TFR2 has been shown to mediate iron transport in vitro and regulate iron homeostasis. The aim of this study was to determine the role of Tfr2 in iron transport in vivo using a Tfr2 mutant mouse. Tfr2 mutant and wild-type mice were injected intravenously with 59Fe-transferrin and tissue 59Fe uptake was measured. Tfr1, Tfr2 and ferroportin expression was measured by real-time PCR and Western blot. Cellular localisation of ferroportin was determined by immunohistochemistry. Transferrin-bound iron uptake by the liver and spleen in Tfr2 mutant mice was reduced by 20% and 65%, respectively, whilst duodenal and renal uptake was unchanged compared with iron-loaded wild-type mice. In Tfr2 mutant mice, liver Tfr2 protein was absent, whilst ferroportin protein was increased in non-parenchymal cells and there was a low level of expression in hepatocytes. Tfr1 expression was unchanged compared with iron-loaded wild-type mice. Splenic Tfr2 protein expression was absent whilst Tfr1 and ferroportin protein expression was increased in Tfr2 mutant mice compared with iron-loaded wild-type mice. A small reduction in hepatic transferrin-bound iron uptake in Tfr2 mutant mice suggests that Tfr2 plays a minor role in liver iron transport and its primary role is to regulate iron metabolism. Increased ferroportin expression due to decreased hepcidin mRNA levels is likely to be responsible for impaired splenic iron uptake in Tfr2 mutant mice.
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影响因子：
168.9
作者：
Bridle, KR;Frazer, DM;Ramm, GA
通讯作者：
Ramm, GA
影响因子：
20.3
作者：
Johnson, MB;Enns, CA
通讯作者：
Enns, CA
影响因子：
13.5
作者：
Chua, Anita C. G.;Herbison, Carly E.;Trinder, Debbie
通讯作者：
Trinder, Debbie
DOI：
10.1038/icb.1954.82
发表时间：
1954-01-01
期刊：
AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE
影响因子：
--
作者：
KALDOR, I
通讯作者：
KALDOR, I
影响因子：
25.7
作者：
Graham, Ross M.;Reutens, Gail M.;Trinder, Debbie
通讯作者：
Trinder, Debbie