植物铁吸收、转运和调控的分子机制研究进展

铁是植物正常生命活动所必需的微量矿质元素,铁离子的吸收、转运和利用是一个复杂的过程,很多基因参与了这一过程。本文对近10年来发现和分离的参与植物铁吸收、转运及调控的基因研究进展进行了综述。根据最近的研究结果,提出了植物控制铁吸收的分子调控模式(机理I)。     

铁转运机制与相关基因的研究进展

铁素营养分子生物学方面的研究有了很大进展。人们利用各种特异突变株和差异筛选已克隆到部分与铁转运有关的基因。本文主要在分子生物学水平概括了酵母铁吸收转运机制和植物缺铁胁迫相关基因及其基因表达的研究进展。     

铁转运机制与相关基因的研究进展

铁素营养分子生物学方面的研究有了很大进展。人们利用各种特异突变株和差异筛选已克隆到部分与铁转运有关的基因。本文主要在分子生物学水平概括了酵母铁吸收转运机制和植物缺铁胁迫相关基因及其基因表达的研究进展。     

高等植物中铁的代谢机制

铁在高等植物的生长发育中发挥着重要作用,但随着人类的耕作及土壤的盐碱化,缺铁已成为一个世界性植物营养问题。高等植物在长期的进化过程中,形成了完善的对环境铁信号响应的体系。本文围绕植物与环境的相互作用,综述了近年来植物铁营养的吸收、转运、分配和储存的研究进展,并总结了植物中铁营养代谢调控的相关机理。     

膜铁转运蛋白1，铁调素的靶分子？

膜铁转运蛋白1是重要的跨膜铁输出分子,主要分布于十二指肠和单核巨噬系统的细胞膜上,参与机体的肠铁吸收和巨噬细胞对铁的再循环等过程。铁调素是调节机体铁代谢平衡的激素,机体通过肝脏分泌的铁调素对铁转运相关蛋白的表达进行调控,从而实现机体自身的铁稳态。最新研究显示,铁调素的靶分子可能是膜铁转运蛋白1,它通过直接的作用引起膜铁转运蛋白1的内化(internalization)、降解,从而调节其在细胞膜上的表达量,进而控制肠铁吸收和巨噬细胞对铁的再循环过程,以维持机体的铁稳态。     

高等植物硝酸盐转运蛋白的功能及其调控机制

硝酸盐是植物从土壤中吸收的重要无机氮素形态。植物为适应含有不同浓度NO3-的土壤环境,进化出了高亲和硝酸盐转运系统(HATS)和低亲和硝酸盐转运系统(LATS),两个基因家族NRT1和NRT2家族分别参与了LATS和HATS的NO3-的吸收和转运。近年来,随着分子生物学技术和植物基因组学的快速发展,研究人员克隆出了大量参与硝酸盐吸收和转运的基因,并对这些基因的功能进行了深入研究,逐渐形成了复杂的硝酸盐调控网络。综述了植物中硝酸盐转运蛋白基因的克隆、表达及调控,并对进一步的研究作了展望,这些结果对于理解植物硝酸盐吸收的调控机制具有重要作用。     

与植物镉吸收转运相关的主要基因家族

镉(cadmium)是一种对植物毒性极强的非必需微量元素,影响植物生长发育,甚至死亡,并可在植物体内积累而威胁食物链顶端生物的生命健康。目前已发现有多类基因家族的成员参与了植物中镉的吸收转运过程,包括P型ATP酶、ABC、MATE、NRAMP、CE、CAX、ZIP、OPT等。这些基因家族主要是在吸收转运铁、锌、镁等植物必需微量元素的同时,也具有吸收转运镉等有毒重金属的功能。     

小肠铁释放机制及相关疾病研究进展

铁是生物体必需的微量元素。铁缺乏和铁过载均会导致铁代谢紊乱相关疾病,因此有关机体铁水平稳态的调节机制已成为了目前铁代谢领域的研究热点。小肠吸收细胞是调节肠铁吸收、肠铁释放,以及维持机体铁稳态的重要部位。最新的研究表明,铁从小肠吸收细胞基底端释放入血液循环,主要是由膜铁转运蛋白（ferroportin1,Fp1）介导,并在膜铁转运辅助蛋白（haphaestin,Hp）和铜蓝蛋白（ceruloplasmin,Cp）的参与下完成。其中Fp1在小肠铁释放过程中起着至关重要的作用。本文重点阐述铁释放相关蛋白Fp1的作用机制及其调节机制,并详细介绍Fp1基因突变导致的铁代谢相关疾病方面的最新研究讲展。     

ZIP蛋白在植物中的功能分析

锌和铁是植物生长发育所必需的微量营养元素,在植物的光合作用、呼吸作用以及许多生化反应中起着非常重要的作用。植物体内锌铁处于平衡状态才能保证其正常的生长发育,而锌铁调控转运体ZIP对于锌铁吸收、转运及体内平衡的调节有重要作用。目前,对于植物中ZIP家族基因的研究有一定进展。对植物ZIP基因的表达、蛋白定位、酵母互补实验、过表达及基因敲除等研究结果进行综述,揭示了ZIP蛋白在植物发育过程中的作用。了解ZIP对于锌铁吸收、转运及体内平衡中的作用有助于通过转基因改良及常规育种将ZIP蛋白应用于农业生产上。     

Structural biology of bacterial iron uptake

To fulfill their nutritional requirement for iron, bacteria utilize various iron sources which include the host proteins transferrin and lactoferrin, heme, and low molecular weight iron chelators termed siderophores. The iron sources are transported into the Gram-negative bacterial cell via specific uptake pathways which include an outer membrane receptor, a periplasmic binding protein (PBP), and an inner membrane ATP-binding cassette (ABC) transporter. Over the past two decades, structures for the proteins involved in bacterial iron uptake have not only been solved, but their functions have begun to be understood at the molecular level. However, the elucidation of the three dimensional structures of all components of the iron uptake pathways is currently limited. Despite the low sequence homology between different bacterial species, the available three-dimensional structures of homologous proteins are strikingly similar. Examination of the current three-dimensional structures of the outer membrane receptors, PBPs, and ABC transporters provides an overview of the structural biology of iron uptake in bacteria.     

Structural biology of bacterial iron uptake

To fulfill their nutritional requirement for iron, bacteria utilize various iron sources which include the host proteins transferrin and lactoferrin, heme, and low molecular weight iron chelators termed siderophores. The iron sources are transported into the Gram-negative bacterial cell via specific uptake pathways which include an outer membrane receptor, a periplasmic binding protein (PBP), and an inner membrane ATP-binding cassette (ABC) transporter. Over the past two decades, structures for the proteins involved in bacterial iron uptake have not only been solved, but their functions have begun to be understood at the molecular level. However, the elucidation of the three dimensional structures of all components of the iron uptake pathways is currently limited. Despite the low sequence homology between different bacterial species, the available three-dimensional structures of homologous proteins are strikingly similar. Examination of the current three-dimensional structures of the outer membrane receptors, PBPs, and ABC transporters provides an overview of the structural biology of iron uptake in bacteria.     

New insights into iron acquisition by cyanobacteria: an essential role for ExbB-ExbD complex in inorganic iron uptake

Cyanobacteria are globally important primary producers that have an exceptionally large iron requirement for photosynthesis. In many aquatic ecosystems, the levels of dissolved iron are so low and some of the chemical species so unreactive that growth of cyanobacteria is impaired. Pathways of iron uptake through cyanobacterial membranes are now being elucidated, but the molecular details are still largely unknown. Here we report that the non-siderophore-producing cyanobacterium Synechocystis sp. PCC 6803 contains three exbB-exbD gene clusters that are obligatorily required for growth and are involved in iron acquisition. The three exbB-exbDs are redundant, but single and double mutants have reduced rates of iron uptake compared with wild-type cells, and the triple mutant appeared to be lethal. Short-term measurements in chemically well-defined medium show that iron uptake by Synechocystis depends on inorganic iron (Fe′) concentration and ExbB-ExbD complexes are essentially required for the Fe′ transport process. Although transport of iron bound to a model siderophore, ferrioxamine B, is also reduced in the exbB-exbD mutants, the rate of uptake at similar total [Fe] is about 800-fold slower than Fe′, suggesting that hydroxamate siderophore iron uptake may be less ecologically relevant than free iron. These results provide the first evidence that ExbB-ExbD is involved in inorganic iron uptake and is an essential part of the iron acquisition pathway in cyanobacteria. The involvement of an ExbB-ExbD system for inorganic iron uptake may allow cyanobacteria to more tightly maintain iron homeostasis, particularly in variable environments where iron concentrations range from limiting to sufficient.     

Dual regulation of the Arabidopsis high-affinity root iron uptake system by local and long-distance signals

Regulation of the root high-affinity iron uptake system by whole-plant signals was investigated at the molecular level in Arabidopsis, through monitoring FRO2 and IRT1 gene expression. These two genes encode the root ferric-chelate reductase and the high-affinity iron transporter, respectively, involved in the iron deficiency-induced uptake system. Recovery from iron-deficient conditions and modulation of apoplastic iron pools indicate that iron itself plays a major role in the regulation of root iron deficiency responses at the mRNA and protein levels. Split-root experiments show that the expression of IRT1 and FRO2 is controlled both by a local induction from the root iron pool and through a systemic pathway involving a shoot-borne signal, both signals being integrated to tightly control production of the root iron uptake proteins. We also show that IRT1 and FRO2 are expressed during the day and down-regulated at night and that this additional control is overruled by iron starvation, indicating that the nutritional status prevails on the diurnal regulation. Our work suggests, for the first time to our knowledge, that like in grasses, the root iron acquisition in strategy I plants may also be under diurnal regulation. On the basis of the new molecular insights provided in this study and given the strict coregulation of IRT1 and FRO2 observed, we present a model of local and long-distance regulation of the root iron uptake system in Arabidopsis.     

Role of siderophore in iron uptake in cowpea Rhizobium GN1 (peanut isolate): Possible involvement of iron repressible outer membrane proteins

Abstract Siderophore produced by cowpea Rhizobium GN1 (Peanut isolate) was shown to be involved in iron uptake by this organism. Siderophore enhanced iron uptake in iron-starved cells. SDS-PAGE analysis of the outer membrane proteins showed two iron repressible outer membrane proteins with approximate molecular mass of 80 kDa and 76 kDa. A siderophore non-producing mutant, which was unable to grow on a medium containing synthetic iron chelators unless and until iron was added exogenously in the medium, could use siderophore of the wild-type for iron uptake indicating that the receptor for Fe-siderophore complex was intact in the mutant.     

Transferrin receptor-dependent iron uptake is responsible for doxorubicin-mediated apoptosis in endothelial cells: role of oxidant-induced iron signaling in apoptosis

In the past, investigators have successfully used iron chelators to mitigate the cardiotoxicity of doxorubicin (DOX), a widely used anticancer drug that induces reactive oxygen species (ROS), oxidative damage, and apoptosis. Although intracellular iron plays a critical role in initiating DOX-induced apoptosis, the molecular mechanism(s) that link iron, ROS, and apoptosis are still unknown. In this study, we demonstrate that apoptosis results from the exposure of bovine aortic endothelial cells to DOX and that the apoptotic cell death is accompanied by a significant increase in cellular iron ((55)Fe) uptake and activation of iron regulatory protein-1. Furthermore, DOX-induced iron uptake was shown to be mediated by the transferrin receptor (TfR)-dependent mechanism. Treatment with the anti-TfR antibody (IgA class) dramatically inhibited DOX-induced apoptosis, iron uptake, and intracellular oxidant formation as measured by fluorescence using dichlorodihydrofluorescein. Treatment with cell-permeable iron chelators and ROS scavengers inhibited DOX-induced cellular (55)Fe uptake, ROS formation, and apoptosis. Based on these findings, we conclude that DOX-induced iron signaling is regulated by the cell surface TfR expression, intracellular oxidant levels, and iron regulatory proteins. The implications of TfR-dependent iron transport in oxidant-induced apoptosis in endothelial cells are discussed.     

Humic acid and iron uptake by plants

Summary The behaviour of ferric EDTA and ferric citrate in nutrient solution and their interaction with humic acid was investigated at various hydrogen ion concentrations using the technique of membrane ultrafiltration to separate small iron species from high molecular weight products of hydrolysis and to estimate the binding of iron by humic acid. Ferric EDTA was found to be of small molecular size at all pH values between 5.0 and 7.0 whilst ferric citrate solutions contained an increasing proportion of high molecular weight material as pH was increased from 5.0 to 7.0. Some iron present in solutions of both ferric EDTA and ferric citrate was bound by humic acid at all pH values from 5.0 to 7.0. Studies were also made of the uptake of iron by wheat roots from nutrient solutions containing either ferric EDTA or ferric citrate and of the effect of humic acid on uptake. More iron was absorbed from ferric EDTA than from ferric citrate at all pH values. Increasing pH between 5.0 and 7.0 resulted in a progressive decrease in the uptake of iron in both cases. The presence of humic acid depressed iron absorption from both solutions at all pH values.     

The effect of ligands on the uptake of iron by cells in culture.

Uptake of iron by a mammalian epithelial cell line (CNCM I-221) was shown to be dependent on the nature of the iron complex. Iron uptake was demonstrated by cytochemical staining and determination of redox-reactive iron in cell lysates. Three classes of ligands were investigated: (i) low molecular weight hydrophilic compounds, represented by ethylenediamine-tetraacetic acid (EDTA) and other charged ligands such as adenosine phosphates (ATP, ADP, AMP) and diethylenetriaminepentaacetic acid (DTPA), (2) low-molecular weight lipophilic ligands such as 8-hydroxyquinoline (8-HQ) and (3) a high molecular mass ligand, dextran. Iron complexed to 8-HQ accumulated intracellularly, the uptake rate of iron being 4.16 fmoles cell-1 h-1 of exposure at 37 degrees C or 3.86 fmoles cell-1 h-1 at 4 degrees C. Iron-dextran was endocytosed and retained in phagosomes. The uptake rate of iron following exposure to iron dextrans was found to be 5.6 fmoles cell-1 h-1 of exposure at 37 degrees C. In contrast to iron/8-HQ, uptake of iron dextran by cells was inhibited at 4 degrees C. Iron complexed to low molecular weight hydrophilic ligands was not taken up by cells. Cytotoxicity was measured by reduction of plating efficiency or tritiated thymidine incorporation. These tests showed that toxic effects of added iron were demonstrable only in cells exposed to the complex with 8-HQ.     

微生物嗜铁素介导的铁摄取

嗜铁素是好氧菌和兼性厌氧菌的一种产物,它是微生物在低铁条件下产生的小分子的、特异性的Fe^3＋螯合因子。大多数的好氧和兼性厌氧微生物至少合成一种嗜铁素,由嗜铁素介导的铁摄取可能是细菌最普遍的一种获取铁元素的方式。