血红素加氧酶-1在铁代谢中的作用

铁是机体必需的微量元素,有着广泛的生物学作用,包括氧化运输和细胞呼吸作用,缺铁会引起细胞生长停滞或死亡,铁过载会使细胞发生氧化应激进而损伤细胞膜、蛋白质、核酸.血红素加氧酶-1(HO-1)分解血红素产生铁是铁重复利用最主要的来源,在铁代谢中的作用至关重要.     

脂多糖对巨噬细胞铁代谢的影响

目的检测二价金属离子转运体(DMT1)和金属转运蛋白(FPN1)在原代培养巨噬细胞中的分布及脂多糖(LPS)对巨噬细胞铁代谢的影响。方法采用原代细胞培养、MTT显色、细胞化学染色和细胞免疫荧光等方法检测LPS对原代培养的巨噬细胞活性的作用及对DMT1和FPN1分布的影响。结果不带铁反应元件的二价金属离子转运体(DMT1-IRE)主要在细胞核中表达,在细胞质中分布较少。带铁反应元件的二价金属离子转运体(DMT1+IRE)主要分布于细胞质中,可以将吞噬小体中的铁向细胞质中转运。FPN1在巨噬细胞的细胞质和细胞膜均有表达,但主要分布于细胞质。结论巨噬细胞吞噬衰老的红细胞以后,其中的亚铁血红素在细胞质中分解,FPN1可能介导了亚铁血红素分解释放出来的铁在巨噬细胞质中的转运过程。LPS在低浓度时有促进巨噬细胞生长的作用,LPS浓度为10-5μg/L时达到高峰,随着浓度的增加,又开始抑制细胞生长。     

铁调素干预成骨细胞(hFOB1.19)后细胞膜转铁蛋白1、铁离子、矿化及成骨基因变化研究

目的 探讨铁调素对成骨细胞铁代谢指标、骨代谢指标的影响和相互关系。方法 成骨细胞 （hFOB1.19）培养3d后,使用逆转录-聚合酶链反应（RT-PCR）检测成骨细胞（hFOB1.19）的膜转铁蛋白1 （ferroportin1,Fpn1）的表达;再用不同浓度的铁调素（25noml/L,50noml/L,100noml/L）干预培养 环境,对照组加相同体积双蒸水,干预20h,MTT法检测细胞增殖情况;激光共聚焦扫描显微镜（CLSM）检 测成骨细胞内铁离子荧光染色后荧光强度变化情况;Von Kossa染色检测成骨细胞矿化情况;RT-PCR检测 骨钙素（BGP）、I型胶原（COL1）、骨保护素（OPG）基因表达。结果 1、成骨细胞存在Fpn1表达;2、铁 调素对成骨细胞增殖无显著影响（P>0.05）;3、铁调素干预后,成骨细胞内铁离子含量增多,且与铁调 素干预存剂量依赖性关系（P<0.05）;4、铁调素干预后,成骨细胞矿化功能增强,且与铁调素干预存剂 量依赖性关系（P<0.05）;5、RT-PCR检测显示不同浓度铁调素干预后,各组COL1、OPG、BGP mRNA均有表 达;不同浓度组的COL1、OPG、BGP mRNA表达光密度比值不同,组间密度比值比较存在统计学意义 （P<0.05）,但铁调素在400nmol/L时抑制OPG的表达（P<0.05）。结论 成骨细胞存在铁调素作用的膜转 铁蛋白-1,所以铁调素干预成骨细胞培养环境后细胞内铁离子发生特异性变化,同时细胞矿化指标显著增 加、细胞COL1、OPG、BGP mRNA表达含量增加;研究提示：铁调素可能通过膜转铁蛋白影响成骨细胞铁离 子变化,细胞铁代谢变化可能引起细胞成骨指标上调改变。     

The SLC40 basolateral iron transporter family (IREG1/ferroportin/MTP1)

The iron regulated-transporter-1 (Ireg1, also known as ferroportin or metal transporter protein-1, MTP1) appears to be the sole member of the SLC40 transporter family. It functions as a universal efflux pathway for iron in a number of cell types. The protein is most highly expressed in mature enterocytes of the duodenum, in syncytiotrophoblasts, which separate foetal and maternal circulations in the placenta, and in macrophages responsible for recycling iron from breakdown of aged red blood cells.     

Iron delocalisation in the pathogenesis of malarial anaemia

There is consensus that the pathophysiology of malaria-associated anaemia is multifactorial, but the precise mechanisms behind many of the haematological changes during malaria remain unclear. In this review, we attempt to build a composite picture of the pathophysiology of malarial anaemia using evidence from experimental, human and animal studies. We propose that cytokine- and hepcidin-mediated iron delocalisation, a principal mechanism in the anaemia of inflammation, plays an important role in the aetiology of malarial anaemia, and can explain some of the clinical and laboratory findings. These mechanisms interact with other aetiological determinants, such as dietary iron and micronutrient supply, helminth load, other infections and genetic variation, in determining the severity and associated features of anaemia. We suggest that iron delocalisation as a mechanism for malarial anaemia could be exploited for the development of alternative therapeutic strategies for post-malaria anaemia.     

A novel ferroportin mutation in a Canadian family with autosomal dominant hemochromatosis

We report a new mutation, Asn185Asp, in exon 6 of the ferroportin gene (FPN1) in 15 members of three successive generations of a Canadian family of Scandinavian origin with autosomal dominant hemochromatosis. Hyperferritinemia with low transferrin saturation was noted in younger family members, seven of whom were aged 20 years or less at the time of diagnosis. In those individuals first diagnosed with hemochromatosis in later life, marked hyperferritinemia was accompanied by high transferrin saturation. In contrast to the phenotype of high ferritin with low saturation first reported for ferroportin disease, this family demonstrates a phenotype of iron indices that varies with age.     

Does the SLC40A1 gene modify HFE-related haemochromatosis phenotypes?

Most hereditary haemochromatosis patients are homozygous for the C282Y mutation of the HFE gene. However, the phenotypic expression and clinical aggressiveness of the disease differs considerably from patient to patient. The main objective of this work was to study the role of variants in the SLC40A1 gene in the severity of iron overload and his clinical consequences in 100 Spanish probands homozygous for the C282Y mutation of the HFE gene. We performed automated sequencing of the coding regions, including intron–exon junctions of the SLC40A1 gene. We studied the association between polymorphisms in the SLC40A1 gene and median values of iron removed, taking into account statistical corrections for multiple comparisons. No pathogenic mutations in the SLC40A1 were detected. Five known single nucleotide polymorphisms (SNPs) were identified, and two of them were associated with phenotypic characteristics. IVS1-24 C>G was associated with the amount of iron removed and presence of liver disease: Of the 83 patients finally studied for this SNP, the amount of iron removed was above the median in 36 of 56 (64.3%) for C/C, in nine of 23(39.1%) for C/G and in zero of four (0%) for G/G patients (P = 0.01). Liver damage was observed in 34 of 56 patients (60.7%) for C/C, in eight of 23 (34.8%) for C/G and in zero of four (0%) for G/G (P = 0.01). Both associations remained significant at multivariate analysis (P = 0.011 and P = 0.023, respectively). IVS1-24 C>G on the ferroportin gene seems to be a genetic modifier for clinical aggressiveness of HFE1 haemochromatosis.