膜铁转运辅助蛋白研究进展

膜铁转运辅助蛋白（Hp） 是研究性连锁遗传贫血（sla）小鼠时发现的一种新的铁转运相关蛋白．它与铜蓝蛋白（Cp）属同一家族．与Cp不同， Hp是具有一个跨膜结构的完整膜蛋白，主要存在于小肠绒毛的上皮细胞．作为亚铁氧化酶，Hp在铁从肠上皮细胞转运到血液的过程是必需的，该基因突变将造成机体严重的铁缺乏．脑内Hp的发现，为脑铁稳态的调控机制提供了新的认识．文中综述了Hp的发现、结构、表达、调控及其在脑铁代谢中的作用．     

小肠微血管内皮细胞铁转运相关蛋白的发现

选用未离乳的SD大鼠十二指肠,采用2次酶消化及不同孔径滤网分级过滤等方法分离十二指肠微血管,通过体外培养、纯化成功获得了高纯度的原代培养的小肠微血管内皮细胞,并应用Western-blot技术,首次检测到了小肠微血管内皮细胞具有铁转运相关蛋白DMT1(divalent metal transporter1),FPN1(feerroportin1)和Tfr1的表达.这一新发现极大地丰富了小肠铁吸收及小肠铁吸收调节机制的理论,对进一步开展小肠铁代谢及其调节机制和铁代谢疾病的研究具有重要的理论和应用价值.     

肝脏抗菌多肽在铁代谢中的调节作用

人体存在着严格的铁代谢调节机制,以确保体内铁始终处于正常生理水平.这种机体铁稳态关键依赖于小肠铁吸收和机体铁需要之间的平衡.研究显示肝脏抗菌多肽很可能是一种控制小肠铁吸收及调节体内铁稳态的关键物质,是一种极为重要的铁调节激素.肝脏抗菌多肽可以反映体内铁的储存状态,在铁积聚时肝脏抗菌多肽表达增加,使小肠铁吸收减少,巨噬细胞铁储存增多;铁缺乏时肝脏抗菌多肽表达减少,使小肠铁吸收增加,巨噬细胞释放铁增加.     

铁调素(Hepcidin)对细胞铁代谢影响的研究进展

Hepcidin是一种肝脏分泌的富含半胱氨酸的新型抗菌多肽,具有抗细菌和真菌等抗菌肽的特性.近几年的研究证实,Hepcidin在机体铁代谢平衡的调节中起关键作用,因而被人们称为铁调节激素.Hepcidin自肝细胞中合成之后分泌至血液,将体内铁调节的信号传至十二指肠细胞、巨噬细胞、脑细胞、心肌细胞等,通过影响铁转运相关蛋白的表达水平,进而调节机体铁的吸收、储存和转运.     

鳗弧菌质粒编码的铁吸收系统的分子调控

鳗弧菌是鱼类弧菌病的主要病原菌，该菌中质粒编码的铁吸收系统是重要的毒力因子．在铁吸收系统中，铁转运体系以及弧菌素合成基因受到AngR、TAF、Fur、反义RNAs、铁离子以及弧菌素等调控因子的调节，这些调控因子分别在转录或后转录水平参与铁吸收系统的正负调控、     

铁缺乏相关儿童睡眠障碍研究进展

 铁缺乏是儿童最常见的微量营养素缺乏症。中国缺铁儿童数量众多，尤其婴幼儿是铁缺乏的高发人群；睡眠是机体发育、修复、调整的重要环节，良好的睡眠对发育中的个体尤其重要。近年来，研究发现铁缺乏可能与几类常见的儿童睡眠障碍有关。从临床特点、病理机制和补铁治疗等方面，回顾了国内外铁缺乏相关儿童睡眠障碍的研究前沿成果。研究结果表明，铁缺乏可能通过引起神经递质紊乱，影响神经髓鞘和树突的形成等途径，导致缺铁儿童睡眠中异常活动增多，补铁治疗被发现可改善部分患儿的睡眠运动症状。     

单核巨噬细胞系统铁代谢调控机制

机体存在着严格的铁代谢调节机制,确保体内的铁始终处于正常的生理水平。单核巨噬细胞系统（mononuclear phagocyte system,包括单核细胞、巨噬细胞及其前体细胞）在机体铁稳态的调节过程中起着关键的作用,不仅可以从衰老的红细胞中回收铁,还可以作为过量铁的贮存库,在机体需铁时将其释放到血液。然而,调控这一过程的分子机制还不甚清楚,近年来,随着CD163,天然抵抗力相关巨噬细胞蛋白 1（natural resistance—associated macrophage protein1,Nramp 1）,Z-价金属离子转运蛋白 1（divalent metal transporter 1,DMTl）,HFE（HLA—linked hemechromatosis gene,HFE）,膜铁转运蛋白1（ferroportinl,FPNl）,尤其是铁调素（hepcidin）的相继发现,使人们对单核巨噬细胞系统的铁代谢过程和调控机制有了较为全面的了解,为人们正确理解机体铁稳态和相关疾病提供了很大帮助。     

两个Caco-2细胞系模型铁生物有效性评价效果研究

研究Caco-2细胞吸收转运模型(模型Ⅰ)和吸收转化模型(模型Ⅱ)对铁生物有效性的评价效果.用不同浓度,pH的硫酸亚铁溶液及稻米分别处理两种模型的Caco-2细胞单层22 h后,测定两种模型细胞铁吸收差异.结果表明Caco-2细胞铁蛋白形成量随铁浓度增加而增加,且模型I高于模型Ⅱ,当铁浓度≥25μmol.L-1时,差异达显著水平(p0.05);细胞铁蛋白形成量和转运铁量均与pH呈负相关,两模型间达到显著相关(p0.05).模型Ⅰ和模型Ⅱ均可用于膳食铁生物有效性评价,高铁浓度时,模型Ⅰ效果优于模型Ⅱ.     

新生儿坏死性小肠结肠炎中细胞死亡机制的研究进展

坏死性小肠结肠炎(Necrotizing Enterocolitis, NEC)是由多因素作用导致的肠道急性炎症性疾病，是早产儿主要的死亡原因之一。以往的研究认为，细胞凋亡是NEC中肠上皮细胞最主要的死亡形式。但近年来的研究发现，程序性坏死(Necroptosis)、细胞焦亡(Pyroptosis)及铁死亡(Ferroptosis)等非凋亡形式的程序性细胞死亡(Programmed Cell Death, PCD)也可能参与到NEC的发病机制中，不同形式的细胞死亡的信号调节通路不同，可能会相互影响或存在共同的调节机制如细胞广泛凋亡小体(PANoptosome)等。本文综述了非凋亡形式的不同类型程序性细胞死亡方式及其信号调节通路，以及其在NEC中的作用机制，并提出NEC诊断生物标志物或防治的新靶点，以期为临床NEC的预防和管理提供思路。     

酵母高亲和力铁转运系统主要基因及环境因子对该系统的影响

Fet3基因编码的一种多铜氧化酶和Ftr1基因编码的一种通透酶介导酵母细胞质膜高亲和力的铁吸收,FET3的Fe(Ⅱ）氧化酶活性是酵母高亲和力铁吸收系统必需的,FTR1在铁的跨膜转运中起着直接的作用,其转运底物是Fe(Ⅲ）,O2通过转录因子AFT1的作用和作为FET3的专性底物而对酵母高亲和力的铁吸收系统起着重要的调节作用。     

细菌铁(Ⅲ)结合蛋白:结构与机理(英文)

铁是生命体必需的微量元素,在大多数环境中铁是有限的资源.高效摄取铁是入侵属主的微生物生存和毒力的关键.许多致病细菌进化出一个特异的铁吸收系统,利用特定的外膜受体和周质铁离子结合蛋白(FBP或FbpA)从属主偷取铁离子.FBP在高效摄取铁的过程中,无论从自由铁源摄取铁或从属主体内转铁蛋白和乳铁蛋白摄取结合的铁,都起着至关重要的作用.FBP的铁结合机制在不同物种间高度保守.结构数据显示,FBP的三维折叠类似于哺乳动物转铁蛋白(TF)的一叶,铁(Ⅲ)在FBP的两个结构域之间的间隙结合但其铁结合位点较其在转铁蛋白中更暴露于溶剂.该小综述总结了FBP铁转运系统,主要讨论了铁结合蛋白的结构和配位化学特征以及铁转运及调控机理.     

Iron metabolism in the mononuclear phagocyte system

The maintenance of body iron homeostasis requires the coordination of multiple regulatory mechanisms of iron metabolism. The mononuclear phagocyte system （MPS, composed of monocytes, macrophages, and their precursor cells） is crucial in the maintenance of iron homeostasis. Recycling of iron is carried out by specialized macrophages via engulfment of aged erythrocytes. The iron stores of macrophages depend on the levels of recovered and exported iron. However, the molecular mechanisms underlying iron homeostasis in macrophages are poorly understood. Recent studies characterizing the function and regulation of natural resistance-associated mac- rophage protein 1 （Nrampl）, divalent metal transporter 1 （DMT1）, HLA-linked hemechromatosis gene （HFE）, ferroportin 1 （FPN1）, and hepcidin are rapidly expanding our knowledge on the molecular level of MPS iron handling. These studies are deepening our under- standing about the molecular mechanism of iron homeostasis and iron-related diseases.     

维生素A缺乏对大鼠生长发育及铁吸收的影响

目的研究维生素A(VA)缺乏对生长期大鼠生长发育及铁吸收的影响.方法将52只雄性SD大鼠,21日龄,按体质量随机分为4组,每组13只,Fe及VA正常对照组(Ⅰ组),Fe正常VA完全缺乏组(Ⅱ组),Fe正常VA轻度缺乏组(Ⅲ组),Fe和VA轻度缺乏组(IV组).实验动物喂饲8周,实验期末,进行72 h代谢实验,记录大鼠的进食量,并收集粪便.代谢实验结束后,处死大鼠,测定血清VA、粪铁含量,计算铁表观吸收率.结果各组动物除Ⅱ组动物性情暴躁、易激惹外,一般状况良好,维生素A缺乏可以使大鼠铁表观吸收率下降(P<0.05).结论维生素A缺乏可能通过影响铁吸收来影响体内铁的营养状况.     

细菌的铁供给研究

在大多数生物机体中，Fe^3 的获得都有着特殊的机制．细菌利用载铁颗粒、铁血红素、血红蛋白来运输铁，并且受基因表达的调控．     

多孔介质中铁的吸附分配和迁移特征

为了掌握多孔介质中铁的吸附分配和迁移特征,采用室内试验和数学模拟的方法,研究了地下水中铁的迁移规律。结果表明:天津市7类多孔介质对铁的吸附均符合Langmuir吸附模式;多孔介质颗粒越细,吸附铁的能力较强,铁迁移滞后系数越大,迁移性越差,颗粒较粗,吸附铁的能力较差,铁迁移滞后系数越小,迁移性越好;在多孔介质中,铁随地下水流动的迁移能力极差。该成果对研究地下水中铁的迁移具有一定的参考价值和指导意义。     

Topological restriction of SNARE-dependent membrane fusion

To fuse transport vesicles with target membranes, proteins of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) complex must be located on both the vesicle (v-SNARE) and the target membrane (t-SNARE). In yeast, four integral membrane proteins, Sed5, Bos1, Sec22 and Bet1 (refs 2-6), each probably contribute a single helix to form the SNARE complex that is needed for transport from endoplasmic reticulum to Golgi. This generates a four-helix bundle, which ultimately mediates the actual fusion event. Here we explore how the anchoring arrangement of the four helices affects their ability to mediate fusion. We reconstituted two populations of phospholipid bilayer vesicles, with the individual SNARE proteins distributed in all possible combinations between them. Of the eight non-redundant permutations of four subunits distributed over two vesicle populations, only one results in membrane fusion. Fusion only occurs when the v-SNARE Bet1 is on one membrane and the syntaxin heavy chain Sed5 and its two light chains, Bos1 and Sec22, are on the other membrane where they form a functional t-SNARE. Thus, each SNARE protein is topologically restricted by design to function either as a v-SNARE or as part of a t-SNARE complex.     

Maize yellow stripe1 encodes a membrane protein directly involved in Fe(III) uptake

Frequently, crop plants do not take up adequate amounts of iron from the soil, leading to chlorosis, poor yield and decreased nutritional quality. Extremely limited soil bioavailability of iron has led plants to evolve two distinct uptake strategies: chelation, which is used by the world's principal grain crops; and reduction, which is used by other plant groups. The chelation strategy involves extrusion of low-molecular-mass secondary amino acids (mugineic acids) known as 'phytosiderophores' which chelate sparingly soluble iron. The Fe(III)-phytosiderophore complex is then taken up by an unknown transporter at the root surface. The maize yellow stripe1 (ys1) mutant is deficient in Fe(III)-phytosiderophore uptake, therefore YS1 has been suggested to be the Fe(III)-phytosiderophore transporter. Here we show that ys1 is a membrane protein that mediates iron uptake. Expression of YS1 in a yeast iron uptake mutant restores growth specifically on Fe(III)-phytosiderophore media. Under iron-deficient conditions, ys1 messenger RNA levels increase in both roots and shoots. Cloning of ys1 is an important step in understanding iron uptake in grasses, and has implications for mechanisms controlling iron homeostasis in all plants.     

The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel

TRPML1 (mucolipin 1, also known as MCOLN1) is predicted to be an intracellular late endosomal and lysosomal ion channel protein that belongs to the mucolipin subfamily of transient receptor potential (TRP) proteins. Mutations in the human TRPML1 gene cause mucolipidosis type IV disease (ML4). ML4 patients have motor impairment, mental retardation, retinal degeneration and iron-deficiency anaemia. Because aberrant iron metabolism may cause neural and retinal degeneration, it may be a primary cause of ML4 phenotypes. In most mammalian cells, release of iron from endosomes and lysosomes after iron uptake by endocytosis of Fe(3+)-bound transferrin receptors, or after lysosomal degradation of ferritin-iron complexes and autophagic ingestion of iron-containing macromolecules, is the chief source of cellular iron. The divalent metal transporter protein DMT1 (also known as SLC11A2) is the only endosomal Fe(2+) transporter known at present and it is highly expressed in erythroid precursors. Genetic studies, however, suggest the existence of a DMT1-independent endosomal and lysosomal Fe(2+) transport protein. By measuring radiolabelled iron uptake, by monitoring the levels of cytosolic and intralysosomal iron and by directly patch-clamping the late endosomal and lysosomal membrane, here we show that TRPML1 functions as a Fe(2+) permeable channel in late endosomes and lysosomes. ML4 mutations are shown to impair the ability of TRPML1 to permeate Fe(2+) at varying degrees, which correlate well with the disease severity. A comparison of TRPML1(-/- )ML4 and control human skin fibroblasts showed a reduction in cytosolic Fe(2+) levels, an increase in intralysosomal Fe(2+) levels and an accumulation of lipofuscin-like molecules in TRPML1(-/-) cells. We propose that TRPML1 mediates a mechanism by which Fe(2+) is released from late endosomes and lysosomes. Our results indicate that impaired iron transport may contribute to both haematological and degenerative symptoms of ML4 patients.