RESUMO
Ferritins are multimeric nanocage proteins that sequester/concentrate excess of free iron and catalytically synthesize a hydrated ferric oxyhydroxide bio-mineral. Besides functioning as the primary intracellular iron storehouses, these supramolecular assemblies also oversee the controlled release of iron to meet physiologic demands. By virtue of the reducing nature of the cytosol, reductive dissolution of ferritin-iron bio-mineral by physiologic reducing agents might be a probable pathway operating in vivo. Herein, to explore this reductive iron-release pathway, a series of quinone analogs differing in size, position/nature of substituents and redox potentials were employed to relay electrons from physiologic reducing agent, NADH, to the ferritin core. Quinones are well known natural electron/proton mediators capable of facilitating both 1/2 electron transfer processes and have been implicated in iron/nutrient acquisition in plants and energy transduction. Our findings on the structure-reactivity of quinone mediators highlight that iron release from ferritin is dictated by electron-relay capability (dependent on E1/2 values) of quinones, their molecular structure (i.e., the presence of iron-chelation sites and the propensity for H-bonding) and the type/amount of reactive oxygen species (ROS) they generate in situ. Juglone/Plumbagin released maximum iron due to their intermediate E1/2 values, presence of iron chelation sites, the ability to inhibit in situ generation of H2O2 and form intramolecular H-bonding (possibly promotes semiquinone formation). This study may strengthen our understanding of the ferritin-iron-release process and their significance in bioenergetics/O2-based cellular metabolism/toxicity while providing insights on microbial/plant iron acquisition and the dynamic host-pathogen interactions.
Assuntos
Ferritinas , Ferro , NAD , Oxirredução , Quinonas , Espécies Reativas de Oxigênio , Ferritinas/química , Ferritinas/metabolismo , Ferro/metabolismo , Ferro/química , NAD/metabolismo , NAD/química , Oxigênio/metabolismo , Oxigênio/química , Quinonas/química , Quinonas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , MycobacteriumRESUMO
Iron deficiency is a global nutritional problem, and adding iron salts directly to food will have certain side effects on the human body. Therefore, there is growing interest in food-grade iron delivery systems. This review provides an overview of iron delivery systems, with emphasis on the controlled release of iron during gastrointestinal digestion, as well as the enhancement of iron absorption and bioavailability. Iron-bearing proteins are easily degraded by digestive enzymes and absorbed through receptor-mediated endocytosis. Instead, protein aggregates are slowly degraded in the stomach, which delays iron release and serves as a potential iron supplement. Amino acids, peptides and polysaccharides can bind iron through iron binding sites, but the formed compounds are prone to dissociation in the stomach. Moreover, peptides and polysaccharides can deliver iron by mediating the formation of ferric oxyhydroxide which is absorbed through endocytosis or bivalent transporter 1. In addition, liposomes are unstable during gastric digestion and iron is released in large quantities. Complexes formed by polysaccharides and proteins, and microcapsules formed by polysaccharides can delay the release of iron in the gastric environment and prolong iron release in the intestinal environment. This review is conducive to the development of iron functional ingredients and dietary supplements.
Assuntos
Suplementos Nutricionais , Ferro , Humanos , Disponibilidade Biológica , Preparações de Ação Retardada , Proteínas , Peptídeos , PolissacarídeosRESUMO
After mine closure and flooding, abandoned iron-prone devices and equipment (e.g., steel bolts and ground support meshes) and iron-bearing minerals (e.g., pyrite) form a dual-source iron pollution system in mine groundwater. Dual-source iron contributes to the water-solid-gas interaction in abandoned coal mines and the release of iron at different periods after mine closure, posing environmental risks in groundwater and discharging acid mine drainage, which contains large amounts of iron. In this study, a series of hydrochemical experiments were conducted to simulate the iron release process of the dual-source system, and electrochemical experiments were carried out to reveal the reaction mechanism, characterize the dual-source iron pollution release mode and quantify the release rate ratio. PHREEQC package was used to simulate the long-term hydrogeochemistry reactions of the water-solid-gas interaction to determine the key factors and suitable conditions that inhibit dual-source iron release. The results show that the dual-source system of iron-bearing minerals (pyrite) and steel bolts promote iron release from each other. The resulting calculated annual iron release indicated that the overall iron release rate ratio is: dual-source > bolt > pyrite, indicating that mine water would remain acidic for a long time due to the continuous release of iron from the system. Numerical modeling results show that maintaining the environment temperature below 25 °C and the pH above 3.5 is an effective way to reduce the iron release rate.
Assuntos
Poluentes Químicos da Água , Água , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Ferro/análise , Minerais , Carvão Mineral , AçoRESUMO
Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), or systemic amyloidosis, are characterized by the specific protein transformation from the native state to stable insoluble deposits, e.g., amyloid plaques. The design of potential therapeutic agents and drugs focuses on the destabilization of the bonds in their beta-rich structures. Surprisingly, ferritin derivatives have recently been proposed to destabilize fibril structures. Using atomic force microscopy (AFM) and fluorescence spectrophotometry, we confirmed the destructive effect of reconstructed ferritin (RF) and magnetoferritin (MF) on lysosome amyloid fibrils (LAF). The presence of iron was shown to be the main factor responsible for the destruction of LAF. Moreover, we found that the interaction of RF and MF with LAF caused a significant increase in the release of potentially harmful ferrous ions. Zeta potential and UV spectroscopic measurements of LAF and ferritin derivative mixtures revealed a considerable difference in RF compared to MF. Our results contribute to a better understanding of the mechanism of fibril destabilization by ferritin-like proteins. From this point of view, ferritin derivatives seem to have a dual effect: therapeutic (fibril destruction) and adverse (oxidative stress initiated by increased Fe2+ release). Thus, ferritins may play a significant role in various future biomedical applications.
Assuntos
Amiloide , Muramidase , Amiloide/metabolismo , Muramidase/química , Ferritinas , Ferro/metabolismoRESUMO
In vitro, reductive mobilization of ferritin iron using suitable electron transfer mediators has emerged as a possible mechanism to mimic the iron release process, in vivo. Nature uses flavins as electron relay molecules for important biological oxidation and oxygenation reactions. Therefore, the current work utilizes three flavin analogues: riboflavin (RF), flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which differ in size and charge but have similar redox potentials, to relay electron from nicotinamide adenine dinucleotide (NADH) to ferritin mineral core. Of these, the smallest/neutral analogue, RF, released more iron (~ three fold) in comparison to the larger and negatively charged FMN and FAD. Although iron mobilization got marred during the initial stages under aerobic conditions, but increased with a greater slope at the later stages of the reaction kinetics, which gets inhibited by superoxide dismutase, consistent with the generation of O2â- in situ. The initial step, i.e., interaction of flavins with NADH played critical role in the iron release process. Overall, the flavin-mediated reductive iron mobilization from ferritins occurred via two competitive pathways, involving the reduced form of flavins either alone (anaerobic condition) or in combination with O2â- intermediate (aerobic condition). Moreover, faster iron release was observed for ferritins from Mycobacterium tuberculosis than from bullfrog, indicating the importance of protein nanocage and the advantages they provide to the respective organisms. Therefore, these structure-reactivity studies of flavins with NADH/O2 holds significance in ferritin iron release, bioenergetics, O2-based cellular toxicity and may be potentially exploited in the treatment of methemoglobinemia. Smaller sized/neutral flavin analogue, riboflavin (RF) exhibits faster reactivity towards both NADH and O2 generating more amount of O2â- and releases higher amount of iron from different ferritins, compared to its larger sized/negatively charged derivatives such as FMN and FAD.
Assuntos
Dinitrocresóis/metabolismo , Ferritinas/metabolismo , Ferro/metabolismo , Mycobacterium tuberculosis/metabolismo , NAD/metabolismo , Oxigênio/metabolismo , Rana catesbeiana , AnimaisRESUMO
CONTEXT: Cigarette smokers develop structural modification in hemoglobin (Hb) and this modification enable Hb to undergo higher rate of auto-oxidation, leading to generation of further intracellular ROS. OBJECTIVE: In this study, we exhibited the possible cause and consequences of Hb modification in cigarette smokers. METHODS: Twenty-two smokers and 16 nonsmokers, aged 25 to 35 years, having a smoking history of 7-10 years were recruited in this study. Carbonyl content, ferryl form, peroxidase-like and esterase-like activities of Hb were assayed. Free iron release by Hb, erythrocyte membrane-bound Hb and plasma Hb were also measured along with assessment of important biomolecular degradations by Hb. RESULTS AND DISCUSSION: Increase in carbonyl content in Hb indicates its oxidative degradation. Increase in ferryl Hb formation, peroxidase-like activity and decrease in esterase like activity of Hb along with increased release of nonheme iron (from Hb) clearly indicates alteration in physico-chemical properties of Hb in smokers. Moreover, increase in erythrocyte membrane-bound Hb and plasma-free Hb provide further evidences for higher rate of Hb oxidation in smokers' erythrocyte. The rates of protein, lipid, sugar and DNA degradation were noticed to be higher by smokers' Hb; and were further attenuated by desferrioxamine as well as mannitol. CONCLUSION: We conclude that in cigarette smokers, there is oxidative degradation of Hb and the degradation causes alteration in its physico-chemical properties, which in turn may degrade different biomolecules in its close vicinity by releasing more iron and production of more superoxide as well as hydroxyl radical.
Assuntos
Hemoglobinas/química , Estresse Oxidativo/efeitos dos fármacos , Fumantes , Adulto , Esterases/metabolismo , Humanos , Masculino , Peroxidase/metabolismoRESUMO
Many problems in drinking water distribution systems (DWDSs) are caused by microbe, such as biofilm formation, biocorrosion and opportunistic pathogens growth. More iron release from corrosion scales may induce red water. Biofilm played great roles on the corrosion. The iron-oxidizing bacteria (IOB) promoted corrosion. However, when iron-reducing bacteria (IRB) and nitrate-reducing bacteria (NRB) became the main bacteria in biofilm, they could induce iron redox cycling in corrosion process. This process enhanced the precipitation of iron oxides and formation of more Fe3O4 in corrosion scales, which inhibited corrosion effectively. Therefore, the IRB and NRB in the biofilm can reduce iron release and red water occurrence. Moreover, there are many opportunistic pathogens in biofilm of DWDSs. The opportunistic pathogens growth in DWDSs related to the bacterial community changes due to the effects of micropollutants. Micropollutants increased the number of bacteria with antibiotic resistance genes (ARGs). Furthermore, extracellular polymeric substances (EPS) production was increased by the antibiotic resistant bacteria, leading to greater bacterial aggregation and adsorption, increasing the chlorine-resistance capability, which was responsible for the enhancement of the particle-associated opportunistic pathogens in DWDSs. Moreover, O3-biological activated carbon filtration-UV-Cl2 treatment could be used to control the iron release, red water occurrence and opportunistic pathogens growth in DWDSs.
Assuntos
Água Potável , Biofilmes , Cloro , Corrosão , Microbiologia da Água , Abastecimento de ÁguaRESUMO
Significant iron release from cast iron pipes in water distribution systems (WDSs), which usually occurs during the source water switch period, is a great concern of water utilities because of the potential occurrence of "red water" and customer complaints. This study developed a new method which combined in-situ water stagnation experiments with mathematical models and numerical simulations to predict the iron release caused by source water switch. In-situ water stagnation experiments were conducted to determine the total iron accumulation in nine cast iron pipes in-service in Beijing when switching the local water to treated Danjiangkou Reservior water. Results showed that the difference in the concentration increment of total iron in 24 hr (ΔCITI,24), i.e. short-term iron release, caused by source water switch was mainly dependent on the difference in the key quality parameters (pH, hardness, nitrate, Larson Ratio and dissolved oxygen (DO)) between the two source waters. The iron release rate (RFe) after switch, i.e. long-term iron release, was closely related to the pipe properties as well as the DO and total residual chlorine (TRC) concentrations. Mathematical models of ΔCITI,24 and RFe were developed to quantitatively reveal the relationship between iron release and the key quality parameters. The RFe model could successfully combine with EPANET-MSX, a numerical simulator of water quality for WDSs to extend the iron release modeling from pipe level to network level. The new method is applicable to predicting iron release during source water switch, thus facilitating water utilities to take preventive actions to avoid "red water".
Assuntos
Água Potável , Ferro , Cloro , Corrosão , Qualidade da Água , Abastecimento de ÁguaRESUMO
6-Hydroxydopamine (6-OHDA), which is a neurotoxin that selectively destroys catecholaminergic nerves in sympathetically innervated tissues, has been used to provide a model of Parkinson's disease in experimental animals. It is rapidly autoxidised to yield potentially toxic products and reactive oxygen species. Its ability to release Fe(II) from protein storage sites also results in the formation of hROS. This account will consider how this family of toxic products may contribute to the observed effects of 6-OHDA.
Assuntos
Modelos Animais de Doenças , Neurotoxinas/farmacologia , Oxidopamina/farmacologia , Doença de Parkinson , Animais , Humanos , Neurotoxinas/toxicidade , Oxidopamina/toxicidadeRESUMO
To evaluate the iron ion release profile of zero-valent iron (ZVI)-based nanoparticles (NPs) and their relationship with lysosomes in cancer cells, silica and mesoporous silica-coated ZVI NPs (denoted as ZVI@SiO2 and ZVI@mSiO2) were synthesized and characterized for the following study of cytotoxicity, intracellular iron ion release, and their underlying mechanisms. ZVI@mSiO2 NPs showed higher cytotoxicity than ZVI@SiO2 NPs in the OEC-M1 oral cancer cell line. In addition, internalized ZVI@mSiO2 NPs deformed into hollow and void structures within the cells after a 24-h treatment, but ZVI@SiO2 NPs remained intact after internalization. The intracellular iron ion release profile was also accordant with the structural deformation of ZVI@mSiO2 NPs. Burst iron ion release occurred in ZVI@mSiO2-treated cells within an hour with increased lysosome membrane permeability, which induced massive reactive oxygen species generation followed by necrotic and apoptotic cell death. Furthermore, inhibition of endosome-lysosome system acidification successfully compromised burst iron ion release, thereby reversing the cell fate. An in vivo test also showed a promising anticancer effect of ZVI@mSiO2 NPs without significant weight loss. In conclusion, we demonstrated the anticancer property of ZVI@mSiO2 NPs as well as the iron ion release profile in time course within cells, which is highly associated with the surface coating of ZVI NPs and lysosomal acidification.
Assuntos
Ferro/uso terapêutico , Nanopartículas Metálicas/efeitos adversos , Neoplasias Experimentais/tratamento farmacológico , Animais , Apoptose , Linhagem Celular Tumoral , Células Cultivadas , Liberação Controlada de Fármacos , Humanos , Ferro/farmacologia , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Masculino , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/químicaRESUMO
BACKGROUND: Ferritin detoxifies excess of free Fe(II) and concentrates it in the form of ferrihydrite (Fe2O3·xH2O) mineral. When in need, ferritin iron is released for cellular metabolic activities. However, the low solubility of Fe(III) at neutral pH, its encapsulation by stable protein nanocage and presence of dissolved O2 limits in vitro ferritin iron release. METHODS: Physiological reducing agent, NADH (E1/2â¯=â¯-330â¯mV) was inefficient in releasing the ferritin iron (E1/2â¯=â¯+183â¯mV), when used alone. Thus, current work investigates the role of low concentration (5-50⯵M) of phenazine based electron transfer (ET) mediators such as FMN, PYO - a redox active virulence factor secreted by Pseudomonas aeruginosa and PMS towards iron mobilization from recombinant frog M ferritin. RESULTS: The presence of dissolved O2, resulting in initial lag phase and low iron release in FMN, had little impact in case of PMS and PYO, reflecting their better ET relay ability that facilitates iron mobilization. The molecular modeling as well as fluorescence studies provided further structural insight towards interaction of redox mediators on ferritin surface for electron relay. CONCLUSIONS: Reductive mobilization of iron from ferritin is dependent on the relative rate of NADH oxidation, dissolved O2 consumption and mineral core reduction, which in turn depends on E1/2 of these mediators and their interaction with ferritin. GENERAL SIGNIFICANCE: The current mechanism of in vitro iron mobilization from ferritin by using redox mediators involves different ET steps, which may help to understand the iron release pathway in vivo and to check microbial growth.
Assuntos
Proteínas de Anfíbios/química , Ferritinas/química , Ferro/química , Modelos Químicos , NAD/química , Proteínas de Anfíbios/metabolismo , Animais , Anuros , Transporte de Elétrons , Ferritinas/metabolismo , Ferro/metabolismo , NAD/metabolismo , Oxirredução , Oxigênio/química , Oxigênio/metabolismoRESUMO
Bacterial community structure and iron corrosion were investigated for simulated drinking water distribution systems (DWDSs) composed of annular reactors incorporating three different treatments: ozone, biologically activated carbon and chlorination (O3-BAC-Cl2); ozone and chlorination (O3-Cl2); or chlorination alone (Cl2). The lowest corrosion rate and iron release, along with more Fe3O4 formation, occurred in DWDSs with O3-BAC-Cl2 compared to those without a BAC filter. It was verified that O3-BAC influenced the bacterial community greatly to promote the relative advantage of nitrate-reducing bacteria (NRB) in DWDSs. Moreover, the advantaged NRB induced active Fe(III) reduction coupled to Fe(II) oxidation, enhancing Fe3O4 formation and inhibiting corrosion. In addition, O3-BAC pretreatment could reduce high-molecular-weight fractions of dissolved organic carbon effectively to promote iron particle aggregation and inhibit further iron release. Our findings indicated that the O3-BAC treatment, besides removing organic pollutants in water, was also a good approach for controlling cast iron corrosion and iron release in DWDSs.
Assuntos
Carvão Vegetal/química , Água Potável/microbiologia , Ozônio/química , Microbiologia da Água , Poluentes Químicos da Água/química , Purificação da Água/métodos , Bactérias , Água Potável/química , Ferro/químicaRESUMO
BACKGROUND: Ferritins are ubiquitous multi-subunit iron storage and detoxification proteins that play a critical role in iron homeostasis. Ferrous ions that enter the protein's shell through hydrophilic channels are rapidly oxidized at dinuclear centers on the H-subunit before transfer to the protein's cavity for storage. The mechanisms of iron loading have been extensively studied, but little is known about iron mobilization. Fe(III) reduction can occur via rapid reduction by suitable reducing agents followed by chelation of Fe(II) ions or via direct and slow Fe(III) chelation. Here, the iron release kinetics from ferritin by FMNH2 in the presence of various chaotropic agents are studied and their in-vivo physiological significance discussed. METHODS: The iron release kinetics from horse and human ferritins by FMNH2 were monitored at 522nm where the Fe(II)-bipyridine complex absorbs. The experiments were performed in the presence of different concentrations of three chaotropic agents, urea, guanidine HCl, and triton. RESULTS AND CONCLUSIONS: Under our experimental conditions, iron reductive mobilization by the non-enzymatic FMN/NAD(P)H system is limited by the concentration of FMNH2 and is independent on the type or amount of chaotropes present. Diffusion of FMNH2 through the ferritin pores is an unlikely mechanism for ferritin iron reduction. An iron mobilization mechanism involving rapid electron transfer through the protein shell is discussed. GENERAL SIGNIFICANCE: Caution must be exercised when interpreting the kinetics of iron mobilization from ferritin using the FMN/NAD(P)H system. The kinetics are highly dependent on the amount of dissolved oxygen and the concentration of reagents used.
Assuntos
Ferritinas/química , Mononucleotídeo de Flavina/farmacologia , Hidroquinonas/farmacologia , Ferro/química , Animais , Transporte de Elétrons , Guanidina/farmacologia , Cavalos , Humanos , Cinética , Octoxinol/farmacologia , Oxirredução , Ureia/farmacologiaRESUMO
Smokers have an elevated risk of cardiovascular disease, but the origin(s) of this increased risk are incompletely defined. Evidence supports an accumulation of the oxidant-generating enzyme myeloperoxidase (MPO) in the inflamed artery wall, and smokers have high levels of SCN(-), a preferred MPO substrate, with this resulting in HOSCN formation. We hypothesised that HOSCN, a thiol-specific oxidant may target the iron-sulphur cluster of aconitase (both isolated, and within primary human coronary artery endothelial cells; HCAEC) resulting in enzyme dysfunction, release of iron, and conversion of the cytosolic isoform to iron response protein-1, which regulates intracellular iron levels. We show that exposure of isolated aconitase to increasing concentrations of HOSCN releases iron from the aconitase [Fe-S]4 cluster, and decreases enzyme activity. This is associated with protein thiol loss and modification of specific Cys residues in, and around, the [Fe-S]4 cluster. Exposure of HCAEC to HOSCN resulted in increased intracellular levels of chelatable iron, loss of aconitase activity and increased iron response protein-1 (IRP-1) activity. These data indicate HOSCN, an oxidant associated with oxidative stress in smokers, can induce aconitase dysfunction in human endothelial cells via Cys oxidation, damage to the [Fe-S]4 cluster, iron release and generation of IRP-1 activity, which modulates ferritin protein levels and results in dysregulation of iron metabolism. These data may rationalise, in part, the presence of increased levels of iron in human atherosclerotic lesions and contribute to increased oxidative damage and endothelial cell dysfunction in smokers. Similar reactions may occur at other sites of inflammation.
Assuntos
Aconitato Hidratase/metabolismo , Deficiências de Ferro , Proteínas Reguladoras de Ferro/metabolismo , Oxidantes/metabolismo , Fumar/metabolismo , Aconitato Hidratase/química , Células Cultivadas , Vasos Coronários/citologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/metabolismo , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Ácido Hipocloroso/farmacologia , Ferro/metabolismo , Oxidantes/química , Relação Estrutura-Atividade , Tiocianatos/farmacologiaRESUMO
BACKGROUND: Extensive in-vitro studies have focused on elucidating the mechanism of iron uptake and mineral core formation in ferritin. However, despite a plethora of studies attempting to characterize iron release under different experimental conditions, the in-vivo mobilization of iron from ferritin remains poorly understood. Several iron-reductive mobilization pathways have been proposed including, among others, flavin mononucleotides, ascorbate, glutathione, dithionite, and polyphenols. Here, we investigate the kinetics of iron release from ferritin by reduced flavin nucleotide, FMNH2, and discuss the physiological significance of this process in-vivo. METHODS: Iron release from horse spleen ferritin and recombinant human heteropolymer ferritin was followed by the change in optical density of the Fe(II)-bipyridine complex using a Cary 50 Bio UV-Vis spectrophotometer. Oxygen consumption curves were followed on a MI 730 Clark oxygen microelectrode. RESULTS: The reductive mobilization of iron from ferritin by the nonenzymatic FMN/NAD(P)H system is extremely slow in the presence of oxygen and might involve superoxide radicals, but not FMNH2. Under anaerobic conditions, a very rapid phase of iron mobilization by FMNH2 was observed. CONCLUSIONS: Under normoxic conditions, FMNH2 alone might not be a physiologically significant contributor to iron release from ferritin. GENERAL SIGNIFICANCE: There is no consensus on which iron release pathway is predominantly responsible for iron mobilization from ferritin under cellular conditions. While reduced flavin mononucleotide (FMNH2) is one likely candidate for in-vivo ferritin iron removal, its significance is confounded by the rapid oxidation of the latter by molecular oxygen.
Assuntos
Ferritinas/metabolismo , Mononucleotídeo de Flavina/metabolismo , Ferro/metabolismo , Animais , Cavalos , Humanos , NAD/metabolismo , Espectrofotometria UltravioletaRESUMO
In the biological systems, exposure to nanoparticles (NPs) can cause complicated interactions with proteins, the formation of protein corona and structural changes to proteins. These changes depend not only on NP physicochemical properties, but also on the intrinsic stability of protein molecules. Although, the formation of protein corona on the surface of NPs and the underlying mechanisms have been fully explored in various studies, no comprehensive review has discussed the direct biochemical and biophysical interactions between NPs and blood proteins, particularly transferrin. In this review, we first discussed the interaction of NPs with proteins to comprehend the effects of physicochemical properties of NPs on protein structure. We then overviewed the transferrin structure and its direct interaction with NPs to explore transferrin stability and its iron ion (Fe3+) release behavior. Afterwards, we surveyed the various biological functions of transferrin, such as Fe3+ binding, receptor binding, antibacterial activity, growth, differentiation, and coagulation, followed by the application of transferrin-modified NPs in the development of drug delivery systems for cancer therapy. We believe that this study can provide useful insight into the design and development of bioconjugates containing NP-transferrin for potential biomedical applications.
Assuntos
Nanopartículas , Coroa de Proteína , Transferrina/química , Coroa de Proteína/química , Nanopartículas/química , Ferro/metabolismo , Ligação ProteicaRESUMO
Serum transferrin (sTf) is a bi-lobal protein. Each lobe of sTf binds one Fe3+ ion in the presence of a synergistic anion. Physiologically, carbonate is the main synergistic anion but other anions such as oxalate, malonate, glycolate, maleate, glycine, etc. can substitute for carbonate in vitro. The present work provides the possible pathways by which the substitution of carbonate with oxalate affects the structural, kinetic, thermodynamic, and functional properties of blood plasma sTf. Analysis of equilibrium experiments measuring iron release and structural unfolding of carbonate and oxalate bound diferric-sTf (Fe2sTf) as a function of pH, urea concentration, and temperature reveal that the structural and iron-centers stability of Fe2sTf increase by substitution of carbonate with oxalate. Analysis of isothermal titration calorimetry (ITC) scans showed that the affinity of Fe3+ with apo-sTf is enhanced by substituting carbonate with oxalate. Analysis of kinetic and thermodynamic parameters measured for the iron release from the carbonate and oxalate bound monoferric-N-lobe of sTf (FeNsTf) and Fe2sTf at pH 7.4 and pH 5.6 reveals that the substitution of carbonate with oxalate inhibits/retards the iron release via increasing the enthalpic barriers.
Assuntos
Carbonatos , Ferro , Ânions/química , Carbonatos/metabolismo , Ferro/química , Cinética , OxalatosRESUMO
Protein-small molecule interactions naturally occur in foodstuffs, which could improve the properties of protein and small molecules. Meanwhile, they might affect the bioavailability and nutritional value of proteins. Ferritin, as an iron-storage protein, has been a focus of research. However, the complexity of foodstuffs enables the interaction between ferritin and food components, especially polyphenols, which can induce iron release from ferritin. Thus, the application of ferritin in food is limited. Inspired by the natural-occurring, strong protein-polyphenol interactions in beer, to inhibit the iron release of ferritin, the malt-derived protein Z (PZ) was chosen to interact with ferulic acid (FA), an abundant reductant in malt, beer, and other foodstuffs. The analysis of the interaction between PZ and FA was carried out using fluorescence spectroscopy, the results of which suggest that one PZ molecule can bind with 22.11 ± 2.13 of FA, and the binding constant is (4.99 ± 2.13) × 105 M-1. In a molecular dynamics (MD) simulation, FA was found to be embedded in the internal hydrophobic pocket of PZ, where it formed hydrogen bonds with Val-389 and Tyr-234. As expected, compared to iron release induced by FA, the iron release from donkey spleen ferritin (DSF) induced by FA decreased by 86.20% in the presence of PZ. Meanwhile, based on the PZ-FA interaction, adding PZ in beer reduced iron release from DSF by 40.5% when DSF:PZ was 1:40 (molar ratio). This work will provide a novel method of inhibiting iron release from ferritin.
RESUMO
Ferritin plays an important role in regulating the homeostasis of iron in cells by storing/releasing iron. Current methods usually explored the determination of iron content, but in-situ imaging of the iron storage/release from ferritin in cells cannot be achieved. Hence, an engineered self-assembled biomimetic-compartmented nanoprobe (APO@CDs) has been constructed. The protein shell of APO (apoferritin) acted as ion channel module to control iron ions entering/exiting ferritin cavity; the inner core of CDs (carbon dots) acted as signal module for iron ions response. Compared with CDs, the response sensitivity and specificity to iron ions (Fe3+) have been improved by using APO@CDs, and the cytotoxicity was significantly reduced. Additionally, compared with cells containing APO@CDs alone, the normalized fluorescence gray value of Fe3+-treated cells was significantly decreased (0.275), indicating that Fe3+ has effectively entered the ferritin. Furtherly, that of Fe3+-treated cells incubated with deferoxamine (DFO) was significantly enhanced (0.712), showing that Fe3+ was released from ferritin under the mediation of DFO. The results demonstrate that APO@CDs can be successfully applied to in-situ imaging of iron storage/release from ferritin in cells, providing a potential platform for the in-situ dynamic study of the iron storage/release in biomedical field.
Assuntos
Ferritinas , Ferro , Ferro/metabolismo , Biomimética , Carbono/metabolismo , FluorescênciaRESUMO
Unlined iron pipe (UIP) is still widely in use in drinking water distribution systems (DWDS), discoloration easily happens after a long-time retention due to iron release, but the influence of initial chlorine on water quality under this condition is not clear. Here, we studied the water quality changes in UIP section reactors under different initial chlorine dosages. Results showed that chlorine could disappeared rapidly within 0.5 h in the UIP. The water with higher initial chlorine (5 mg/L) had higher turbidity in a short time (within 1.5 h), but for a longer retention time (2â¼12 h), the highest turbidity was in the iron pipe without initial chlorine. Interestingly, a clear increase in adenosine triphosphate in the UIPs was observed with the increase of initial chlorine, which was in accordance with the results of heterotrophic plate count. Polysaccharide and protein increased with the increase of initial chlorine, which would benefit the formation of a protective layer to inhibit corrosion. This study reflects that during the overnight retention in UIP, raising chlorine would be effective to control discoloration, but chemical and microbiological risks may increase.