细胞质及线粒体ferritin与铁代谢

铁是机体代谢所必需的微量元素之一。近年来,铁在机体内的代谢越来越受到人们的重视。维持体内铁的平衡,对保证机体的正常生理功能显得极为重要。胞质铁蛋白（cytosolic ferrifin,CFt）是细胞内重要的调节铁平衡的因子之一。而近年发现的线粒体铁蛋白（mitochondrial ferritin,MtFt）是一种定位在线粒上、和铁代谢密切相关的蛋白,具有组织受限性表达的特点,它在结构和功能上与胞质铁蛋白相比有一定的相似性,但是由于其mRNA上没有铁调控元件,它的表达不直接受铁调节蛋白调控,所以其确切功能及表达机制还未完全明了,因此,近年来有不少人开展了这方面的研究。对线粒体铁蛋白的深入研究将极大地丰富人们对铁在亚细胞水平上的代谢机制和功能的认识。文章介绍了细胞质铁蛋白的调控机制以及线粒体铁蛋白的结构、功能、表达及与铁代谢的关系。     

食物源蛋白肽铁配合物的研究进展

综述食物源蛋白多肽铁配合物的制备、分离纯化、结构分析、生物活性以及安全性研究进展。     

铁代谢与铁调素hepcidin

铁是机体必需的营养元素。然而,铁过载则导致细胞的损伤。由于生物体缺少排泄铁的机制,因而,肠铁吸收的调控便成为维持机体铁稳态的关键。新近研究发现hepcidin对机体铁稳态的调节起着至关重要的作用,被人们称为铁调节激素。Hepcidin主要在肝细胞中合成,之后分泌至血液将体内铁需要的信号传至小肠,调控肠铁的吸收。这一过程主要通过调节小肠铁转运相关蛋白的表达而实现。任何影响hepcidin表达的因素都可能破坏体内的铁平衡,造成铁代谢相关疾病。     

极化过程影响巨噬细胞的铁代谢

本文旨在研究巨噬细胞极化过程对自身铁代谢调节的影响.用20 ng/mLγ干扰素(interferon gamma,1FN-γ)刺激猪肺泡巨噬细胞(3D4/2细胞)24 h,诱导其为M1型巨噬细胞,另外用10 ng/mL白细胞介素4(interleukin-4,IL-4)联合10 ng/mL巨噬细胞集落刺激因子(macr...     

铁代谢蛋白在肾脏的表达与功能

最近的研究证实,肾小管细胞具有能力表达包括转铁蛋白受体1(transferrin receptor-1,TfR1)、二价金属离子转运蛋白1(divalent metal transporter-1,DMT1)、膜铁转运蛋白1(ferroportin-1,FPN1)、铁调节蛋白(iron regulatory protein,IRP)和铁调素(hepcidin,Hepc)在内的几乎所有铁代谢蛋白.这些蛋白质的存在以及相关研究显示肾脏可能具有排出多余铁的功能,因此对体铁平衡起有十分重要的作用.     

铁代谢与蛋白质泛素化．降解调控研究进展

铁元素为几乎所有的生命体所必需,维持铁代谢稳态对机体的正常功能至关重要。铁代谢紊乱与人类多种疾病的发生和发展有关。已知铁代谢稳态受到一系列参与铁代谢环节的关键蛋白质,如IRP2等的精确调节。这些重要蛋白质的稳定性、生理活性的动态变化及其协调作用是细胞维持铁代谢平衡的分子基础。除了转录和转录后水平的调控,泛素化等翻译后修饰方式和蛋白质降解是细胞精确调控参与铁代谢的蛋白质的水平及功能普遍而有效的方式之一;同时,细胞的铁代谢状态也影响细胞内参与泛素化等翻译后修饰途径的酶类的活性和稳定性,从而在铁代谢和蛋白质修饰．降解途径之间形成反馈机制,实时和动态地完成对细胞内铁代谢水平的精确调控。就相关领域的最新进展作简要综述。     

去铁酮联合去铁胺治疗重型地中海贫血患儿的疗效及对血糖代谢和铁代谢的影响

目的:探讨去铁酮联合去铁胺治疗重型地中海贫血患儿的疗效及对血糖代谢和铁代谢的影响。方法:选取2015年3月～2017年12月期间海南省妇女儿童医学中心儿科收治的127例重型地中海贫血患儿,根据数表法将患儿随机分为对照组(n=63)和研究组(n=64),其中对照组在基础治疗的基础上给予去铁胺治疗,研究组在对照组的基础上联合去铁酮治疗。比较两组患儿临床疗效、治疗前后的血糖代谢和铁代谢情况,记录两组患儿治疗期间不良反应发生情况。结果:研究组患儿治疗后临床总有效率为73.44%(47/64),高于对照组患儿的55.56%(35/63)(P0.05)。两组患儿治疗后血糖代谢正常率均升高,且研究组高于对照组(P0.05)。两组患儿治疗后血清铁蛋白(SF)降低,尿铁排泄量(UIE)升高(P0.05);研究组治疗后SF低于对照组,UIE高于对照组(P0.05)。两组不良反应发生率比较无统计学差异(P0.05)。结论:去铁酮联合去铁胺治疗重型地中海贫血患儿,安全有效,可改善机体铁代谢,提高血糖代谢正常比例,具有一定的临床应用价值。     

植物黄嘌呤脱氢酶参与代谢途径及其功能研究进展

黄嘌呤脱氢酶(xanthine dehydrogenase,XDH)是一种含钼氧化还原酶,属于钼羟化酶黄蛋白家族,广泛存在于真核生物、细菌和古细菌中。XDH可以催化黄嘌呤和次黄嘌呤生成尿酸,经一系列反应形成尿囊素和尿囊酸。植物中的XDH在嘌呤代谢、氮代谢、激素代谢、活性氧代谢、生物胁迫和非生物胁迫等代谢过程中发挥着重要作用。本文对植物XDH的结构特征、代谢途径、基因家族生物学功能等方面进行了综述,总结了植物嘌呤代谢的分子机制,并对XDH应用前景进行了展望,为作物的生长发育和抗逆性研究提供了参考。     

植物着丝粒结构和功能的研究进展

着丝粒是真核生物有丝分裂和减数分裂染色体正确分离和传递所必需的染色体区域。十多年来, 已对包括拟南芥、水稻、玉米在内的一些植物的着丝粒进行了较深入的分子生物学研究。在不同的植物间, 着丝粒DNA的保守性很低, 呈现快速进化, 但着丝粒的DNA序列类型和组织方式基本相似, 一般是由夹杂排列着的卫星DNA串联重复阵列和着丝粒专一的反转录转座子构成。与着丝粒DNA相反, 着丝粒/着丝点的结构性和瞬时蛋白质在包括植物在内的真核生物中保守。与其他真核生物的情况一样, 拥有含着丝粒组蛋白H3(CENH3)的核小体是植物功能着丝粒染色质最基本的特征, CENH3在着丝粒染色质的识别和保持中起着关键作用。     

生血宁片联合琥珀酸亚铁片治疗妊娠期缺铁性贫血患者的疗效及对铁代谢的影响

目的:探讨生血宁片联合琥珀酸亚铁片治疗妊娠期缺铁性贫血患者的疗效及对铁代谢的影响。方法:选取2015年2月-2017年2月我院收治的妊娠期缺铁性贫血患者200例为研究对象。将其以随机数字表法分成对照组(n=100)和研究组(n=100)。对照组予以口服琥珀酸亚铁片治疗,研究组则予以生血宁片联合琥珀酸亚铁片治疗,两组均连续治疗4周。分别比较两组临床疗效、治疗前后血液学指标、治疗前后铁代谢指标以及不良妊娠结局情况。结果:研究组治疗总有效率明显较对照组升高(P0.05)。治疗后两组患者血红蛋白(Hb)、红细胞(RBC)、平均红细胞体积(MCV)以及平均红细胞血红蛋白浓度(MCHC)水平均明显高于治疗前,且研究组高于对照组(P0.05)。治疗后两组患者血清铁、转铁蛋白饱和度(TSAT)水平均明显高于治疗前,且研究组又明显高于对照组(P0.05)。与对照组比较,研究组不良妊娠结局发生率降低(P0.05)。结论:生血宁片联合琥珀酸亚铁片治疗妊娠期缺铁性贫血患者的临床疗效显著,改善患者血液学指标以及铁代谢水平,降低不良妊娠结局发生风险,值得临床推广应用。     

Current knowledge of iron metabolism

Iron plays many roles in human physiology. In this article, we summarize the basic and current knowledge of this essential micronutrient on human metabolism.     

The effect of chromium on parameters related to iron metabolism

The effect of chromium on some parameters related to iron metabolism was investigated. Preliminary experiments showed that this metal ion was taken up by serum proteins and was dependent on the amount of chromium present in the medium. It was also shown that the uptake of iron was reduced significantly in the presence of chromium. In vivo study showed that the serum levels of iron and total iron binding capacity (TIBC) were reduced by 28 and 11%, respectively, following daily administration of chromium (1 mg/kg) for 45 d. Serum ferritin was reduced by 22% under this condition. Hematocrit and hemoglobin levels were also affected in chromium-treated animals and were both reduced by 17%. Spectrophotometric titration of each individual amino acid located in the iron binding site of transferrin revealed that tyrosin might be the most suitable ligand for the binding of chromium to transferrin. These results suggest that chromium may compete with iron in binding to apo-transferrin, and influence iron metabolism and its related biochemical parameters.     

Distribution and metabolism of iron in muscles of iron-deficient rats

Iron-deficiency anemia leads directly to both reduced hemoglobin levels and work performance in humans and experimental animals. In an attempt to observe a direct link between work performance and insufficient iron at the cellular level, we produced severe iron deficiency in female weanling Sprague-Dawley rats following five weeks on a low-iron diet. Deficient rats were compared with normal animals to observe major changes in hematological parameters, body weight, and growth of certain organs and tissues. The overall growth of iron-deficient animals was approximately 50% of normal. The ratio of organ weight: body weight increased in heart, liver, spleen, kidney, brain, and soleus muscle in response to iron deficiency. Further, mitochondria from heart and red muscle retained their iron more effectively under the stress of iron deficiency than mitochondria from liver and spleen. Metabolism of iron in normal and depleted tissue was measured using tracer amounts of⁵⁹Fe administered orally. As expected, there was greater uptake of tracer iron by iron-deficient animals. The major organ of iron accumulation was the spleen, but significant amounts of isotope were also localized in heart and brain. In all muscle tissue examined the⁵⁹Fe preferentially entered the mitochondria. Enhanced mitochondrial uptake of iron prior to any detectable change in the hemoglobin level in experimental animals may be indicative of nonhemoglobin related biochemical changes and/or decrements in work capacity.     

Effects of dietary supplementation with aluminum and citrate on iron metabolism in the rat

The metabolism of iron (Fe) has been shown to interact with that of aluminum (Al) in relation to intestinal absorption, transport in the blood plasma, and the induction of lipid peroxidation and cellular damage. Also, dietary supplementation with citrate has been shown to increase the absorption of both metals and, in the presence of high intakes of Fe and Al, leads to excessive accumulation of both metals in the body. In this study, the likely interaction between Al and internal Fe metabolism was investigated using rats fed diets that were either deficient, sufficient, or loaded with Fe, with or without the addition of Al and sodium citrate. These diets commenced when the rats were 4 wk old and were continued for 9–11 wk. At that time, Fe metabolism as assessed by measurement of organ uptake of⁵⁹Fe and¹²⁵I-transferrin, after iv injection of transferrin labeled with both isotopes, plus measurement of tissue concentrations of nonheme Fe and Al. The Fedeficient diet and Fe-loaded diet led to states of Fe deficiency and Fe overload in the rats, and supplementation of the diet with Al increased Al levels in the kidneys, liver, and femurs, but, generally, only when the diet also contained citrate. Neither Al nor citrate supplementation of the diet had any effect on nonheme Fe concentrations in the liver, kidney, or brain, or on the uptake of⁵⁹Fe or¹²⁵I-transferrin by liver, kidney, brain, or spleen. Only with the femurs was a significant effect observed: increased⁵⁹Fe uptake in association with increased Al intake. Therefore, using this animal model, there was little evidence for interaction between Fe and Al metabolism, and no support was obtained for the hypothesis that dietary supplementation with Fe and citrate can lead to excessive Fe absorption and deposition in the tissues.     

铁紊乱相关疾病的研究进展

铁作为一种必需的营养元素,在哺乳动物体内的重要作用越来越为人们所重视。动物体内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。如果铁代谢失调、体内铁缺乏或过负荷均会导致各种临床疾病。研究发现,肝脏抗菌多肽(hepcidin)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。本文综述了铁的生理作用、铁缺乏引起的疾病(如:缺铁性贫血和儿童神经系统疾病)和铁过负荷引起的疾病(如:肝损伤、心血管疾病、帕金森病和癌症等),并对如何利用现代化技术手段在基因水平开展铁紊乱相关疾病的治疗做了展望。     

铜稳态对铁代谢平衡的影响

铜是人体必需的微量元素,参与体内多种蛋白和酶的组成,机体内存在严格的铜稳态调控机制。作为血浆中最主要的多铜亚铁氧化酶——铜蓝蛋白,与另外两种同源亚铁氧化酶——膜铁转运辅助蛋白和zyklopen,共同参与体内铁的转运,维持铁代谢的平衡。将对调节铜和铁平衡的重要意义以及铜和铁在机体代谢过程中的相互作用、发展动态进行讨论。     

Effect of exercise on iron metabolism in horses

We investigated the effect of exercise on iron metabolism in horses. Four horses were walked on a mechanical walker for 1 wk (pre-exercise). They then performed moderate exercise on a high-speed treadmill in the first week of the exercise and relative high in the second week and high in the third week. Serum iron was significantly lower in the third week of exercise than in the pre-exercise. Transferrin saturation (TS) was significantly lower in the first and third weeks of exercise than in the pre-exercise. Serum haptoglobin was significantly lower in the first week of exercise than in the pre-exercise and further significantly lower in the second and third weeks than in the first. The packed cell volume did not change during the experiment. The exercise significantly increased the apparent absorption of iron. Urinary iron excretion did not change throughout the experiment. Sweat iron loss did not change during the exercise. The exercise significantly increased iron balance. We considered that hemolysis is induced by moderate exercise and is further enhanced by heavy exercise, which decreases serum iron and TS. However, the increase in iron absorption compensates for the adverse effect of exercise on iron status. Therefore, exercise does not induce anemia in horses.     

Effects of iron deficiency and iron overload on manganese uptake and deposition in the brain and other organs of the rat

Managanese (Mn) is an essential trace element at low concentrations, but at higher concentrations is neurotoxic. It has several chemical and biochemical properties similar to iron (Fe), and there is evidence of metabolic interaction between the two metals, particularly at the level of absorption from the intestine. The aim of this investigation was to determine whether Mn and Fe interact during the processes involved in uptake from the plasma by the brain and other organs of the rat. Dams were fed control (70 mg Fe/kg), Fe-deficient (5–10 mg Fe/kg), or Fe-loaded (20 g carbonyl Fe/kg) diets, with or without Mn-loaded drinking water (2 g Mn/L), from day 18–19 of pregnancy, and, after weaning the young rats, were continued on the same dietary regimens. Measurements of brain, liver, and kidney Mn and nonheme Fe levels, and the uptake of⁵⁴Mn and⁵⁹Fe from the plasma by these organs and the femurs, were made when the rats were aged 15 and 63 d. Organ nonheme Fe levels were much higher than Mn levels, and in the liver and kidney increased much more with Fe loading than did Mn levels with Mn loading. However, in the brain the increases were greater for Mn. Both Fe depletion and loading led to increased brain Mn concentrations in the 15-d/rats, while Fe loading also had this effect at 63 d. Mn loading did not have significant effects on the nonheme Fe concentrations.⁵⁴Mn, injected as MnCl₂ mixed with serum, was cleared more rapidly from the circulation than was⁵⁹Fe, injected in the form of diferric transferrin. In the 15-d-rats, the uptake of⁵⁴Mn by brain, liver, kidneys, and femurs was increased by Fe loading, but this was not seen in the 63-d rats. Mn supplementation led to increased⁵⁹Fe uptake by the brain, liver, and kidneys of the rats fed the control and Fe-deficient diets, but not in the Fe-loaded rats. It is concluded that Mn and Fe interact during transfer from the plasma to the brain and other organs and that this interaction is synergistic rather than competitive in nature. Hence, excessive intake of Fe plus Mn may accentuate the risk of tissue damage caused by one metal alone, particularly in the brain.     

A role of PIEZO1 in iron metabolism in mice and humans

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The determination of ferric iron in plants by HPLC using the microbial iron chelator desferrioxamine E

Common methods for plant iron determination are based on atomic absorption spectroscopy, radioactive measurements or extraction with subsequent spectrophotometry. However, accuracy is often a problem due to background, contamination and interfering compounds. We here describe a novel method for the easy determination of ferric iron in plants by chelation with a highly effective microbial siderophore and separation by high performance liquid chromatography (HPLC). After addition of colourless desferrioxamine E (DFE) to plant fluids, the soluble iron is trapped as a brown-red ferrioxamine E (FoxE) complex which is subsequently separated by HPLC on a reversed phase column. The formed FoxE complex can be identified due to its ligand-to-metal charge transfer band at 435 nm. Alternatively, elution of both, DFE and FoxE can be followed as separate peaks at 220 nm wavelength with characteristic retention times. The extraordinarily high stability constant of DFE with ferric iron of K=10³² enables extraction of iron from a variety of ferrous and ferric iron compounds and allows quantitation after separation by HPLC without interference by coloured by-products. Thus, iron bound to protein, amino acids, citrate and other organic acid ligands and even insoluble ferric hydroxides and phosphates can be solubilized in the presence desferrioxamine E. The “Ferrioxamine E method” can be applied to all kinds of plant fluids (apoplasmic, xylem, phloem, intracellular) either at physiological pH or even at acid pH values. The FoxE complex is stable down to pH 1 allowing protein removal by perchloric acid treatment and HPLC separation in the presence of trifluoroacetic acid containing eluents. Published online December 2004