Iron Release Research Articles

Biological matter enhanced iron release from shallow marine bioturbated sediments: a case study of Late Cretaceous sandstone, northern Saudi Arabia

Biological matter enhanced iron release from shallow marine bioturbated sediments: a case study of Late Cretaceous sandstone, northern Saudi Arabia

Alpha-synuclein Affects Certain Iron Transporters of BV2 Microglia Cell through its ferric reductase activity.

Alpha-synuclein (α-syn) is a major component of lewy bodies, which is biomarker of Parkinson's disease (PD). It accumulates in substantia nigra pars compacts (SNpc) to form insoluble aggregates and cause neurotoxicity, which is often accompanied by iron deposition. In this study, we compared the iron reductase activity between monomeric α-syn (M-α-syn) and oligomeric α-syn (O-α-syn), investigated the effect of α-syn on iron metabolism of BV2 microglia cells as well. We found that α-syn had ferric reductase activity, and O-α-syn had stronger enzyme activity than M-α-syn. M-α-syn upregulated iron uptake protein, divalent metal transporter1 (DMT1) expression and iron influx, but did not regulate iron release protein, ferroportin1 (FPN1) expression and iron efflux. O-α-syn elevated the expression of both DMT1 and FPN1, thus increased the iron influx and efflux in BV2 microglial cells, but the expressions of iron regulatory protein1 and hypoxia inducible factor2α have no significant change. Moreover, both M-α-syn and O-α-syn could increase the mRNA expressions of TNF-α and IL-1β in BV2 microglia cells. Taken together, our data suggest that both types of α-syn can activate microglia, which leads to increased expressions of pro-inflammatory factors. α-syn can affect DMT1 and FPN1 expressions in BV2 microglia cells, which might be through its ferric reductase activity.

Fe(Ⅲ) concentrations controlled highly soluble carboxylated inulin–Fe toward efficient supplement of iron

Iron deficiency is the utmost critical problem of nutrition worldwide. Polysaccharide-iron chelate is a promising iron supplementation that exhibits good stability, high absorption rate, and fewer adverse reactions, but it still owns drawbacks of extra energy and lower iron content with respect to inorganic ones. Carboxylated polysaccharide-iron has been proven with enhanced iron content, however with poor aqueous solubility. Here, Fe3+ concentrations controlled highly soluble carboxylated inulin-iron chelates were synthesized to promote the sustained release and efficient supplement of iron with no extra energy. Inulin, soluble dietary fiber, was initially reacted with succinic anhydride (SA) to get carboxylated inulin (IN-SA) consequently enhancing the complexing ability of Fe3+ and its bioavailability. Interestingly, the aqueous solubility of the IN-SA-iron chelate (IN-SA-Fe) directly correlated with the Fe3+ concentrations. Relatively higher or lower Fe3+ concentrations resulted in highly soluble IN-SA-Fe, otherwise, leading to insolubility precipitates. The possible mechanism was proposed as the polymerization reaction of IN-SA in different degrees with Fe3+ acting as the cross-linker. Moreover, IN-SA-Fe was demonstrated with properties of sustained slow-release of iron in artificial gastric juice and good in vivo biosafety. This work provides a simple, efficient, no extra energy soluble iron supplement for the treatment of iron deficiency.

Sodium nitrite (NaNO2) regulating myoglobin-mediated lipid oxidation in washed bovine mince

ABSTRACT This study investigated the effect of NaNO2 on inhibiting myoglobin-mediated lipid oxidation in muscle using a washed bovine mince model. We measured various parameters, including TBARS and PV to determine lipid oxidation, non-heme iron release, protoporphyrin destruction, and nitrosylmyoglobin production. The results of the study showed that the addition of NaNO2 during myoglobin-mediated lipid oxidation significantly reduced the fading and lipid oxidation of washed muscle (p < 0.05). Additionally, the addition of NaNO2 reduced the release of non-heme iron and the degradation of protoporphyrin in myoglobin. Nitrosylmyoglobin was formed in the washed mince supplemented with NaNO2 and myoglobin. These findings suggest that NaNO2 can effectively inhibit the lipid oxidation process induced by myoglobin, which could be a crucial aspect of nitrite inhibition of lipid oxidation in cured meat products. Overall, the study provides evidence for the potential use of NaNO2 as a food preservative to prevent lipid oxidation in meat products.

Gallium Triggers Ferroptosis through a Synergistic Mechanism.

The gallium ion (Ga3+ ) has long been believed to disrupt ferric homeostasis in the body by competing with iron cofactors in metalloproteins, ultimately leading to cell death. This study revealed that through an indirect pathway, gallium can trigger ferroptosis, a type of non-apoptotic cell death regulated by iron. This is exemplified by the gallium complex of the salen ligand (Ga-1); we found that Ga-1 acts as an effective anion transporter that can affect the pH gradient and change membrane permeability, leading to mitochondrial dysfunction and the release of ferrous iron from the electron transfer chain (ETC). In addition, Ga-1 also targeted protein disulfide isomerases (PDIs) located in the endoplasmic reticulum (ER) membrane, preventing the repair of the antioxidant glutathione (GSH) system and thus enforcing ferroptosis. Finally, a combination treatment of Ga-1 and dietary polyunsaturated fatty acids (PUFAs), which enhances lipid peroxidation during ferroptosis, showed a synergistic therapeutic effect both in vitro and in vivo. This study provided us with a strategy to synergistically induce Ferroptosis in tumor cells, thereby enhancing the anti-neoplastic effect.

Gallium Triggers Ferroptosis through a Synergistic Mechanism

AbstractThe gallium ion (Ga3+) has long been believed to disrupt ferric homeostasis in the body by competing with iron cofactors in metalloproteins, ultimately leading to cell death. This study revealed that through an indirect pathway, gallium can trigger ferroptosis, a type of non‐apoptotic cell death regulated by iron. This is exemplified by the gallium complex of the salen ligand (Ga‐1); we found that Ga‐1 acts as an effective anion transporter that can affect the pH gradient and change membrane permeability, leading to mitochondrial dysfunction and the release of ferrous iron from the electron transfer chain (ETC). In addition, Ga‐1 also targeted protein disulfide isomerases (PDIs) located in the endoplasmic reticulum (ER) membrane, preventing the repair of the antioxidant glutathione (GSH) system and thus enforcing ferroptosis. Finally, a combination treatment of Ga‐1 and dietary polyunsaturated fatty acids (PUFAs), which enhances lipid peroxidation during ferroptosis, showed a synergistic therapeutic effect both in vitro and in vivo. This study provided us with a strategy to synergistically induce Ferroptosis in tumor cells, thereby enhancing the anti‐neoplastic effect.

Ferroptosis induces detrimental effects in chronic EAE and its implications for progressive MS

Ferroptosis is a form of lipid peroxidation-mediated cell death and damage triggered by excess iron and insufficiency in the glutathione antioxidant pathway. Oxidative stress is thought to play a crucial role in progressive forms of multiple sclerosis (MS) in which iron deposition occurs. In this study we assessed if ferroptosis plays a role in a chronic form of experimental autoimmune encephalomyelitis (CH-EAE), a mouse model used to study MS. Changes were detected in the mRNA levels of several ferroptosis genes in CH-EAE but not in relapsing–remitting EAE. At the protein level, expression of iron importers is increased in the earlier stages of CH-EAE (onset and peak). While expression of hemoxygenase-1, which mobilizes iron from heme, likely from phagocytosed material, is increased in macrophages at the peak and progressive stages. Excess iron in cells is stored safely in ferritin, which increases with disease progression. Harmful, redox active iron is released from ferritin when shuttled to autophagosomes by ‘nuclear receptor coactivator 4’ (NCOA4). NCOA4 expression increases at the peak and progressive stages of CH-EAE and accompanied by increase in redox active ferrous iron. These changes occur in parallel with reduction in the antioxidant pathway (system xCT, glutathione peroxidase 4 and glutathione), and accompanied by increased lipid peroxidation. Mice treated with a ferroptosis inhibitor for 2 weeks starting at the peak of CH-EAE paralysis, show significant improvements in function and pathology. Autopsy samples of tissue sections of secondary progressive MS (SPMS) showed NCOA4 expression in macrophages and oligodendrocytes along the rim of mixed active/inactive lesions, where ferritin+ and iron containing cells are located. Cells expressing NCOA4 express less ferritin, suggesting ferritin degradation and release of redox active iron, as indicated by increased lipid peroxidation. These data suggest that ferroptosis is likely to contribute to pathogenesis in CH-EAE and SPMS.

Nickel chloride generates cytotoxic ROS that cause oxidative damage in human erythrocytes

BackgroundNickel is a heavy metal that is regarded as a possible hazard to living organisms due to its toxicity and carcinogenicity. Nickel chloride (NiCl2), an inorganic divalent Ni compound, has been shown to cause oxidative stress in cells by altering the redox equilibrium. We have investigated the effect of NiCl2 on isolated human erythrocytes under in vitro condition. MethodsIsolated erythrocytes were treated with different concentrations of NiCl2 (25–500 µM) for 24 h at 37 ºC. Hemolysates were prepared and several biochemical parameters were analyzed in them. ResultsTreatment of erythrocytes with NiCl2 enhanced the intracellular generation of reactive oxygen species (ROS). A significant increase in hydrogen peroxide levels and oxidation of proteins and lipids was also seen. This was accompanied by a reduction in levels of nitric oxide, glutathione, free amino groups and total sulfhydryl groups. NiCl2 treatment impaired both enzymatic and non-enzymatic defense systems, resulting in lowered antioxidant capacity and diminished ability of cells to quench free radicals and reduce metal ions. NiCl2 exposure also had an inhibitory effect on the activity of enzymes involved in pathways of glucose metabolism (glycolytic and pentose phosphate shunt pathways). Increased level of methemoglobin, which is inactive in oxygen transport, was also seen. The rate of heme breakdown increased resulting in the release of free iron. Exposure to NiCl2 led to considerable cell lysis, indicating damage to the erythrocyte membrane. This was supported by the inhibition of membrane bound enzymes and increase in the osmotic fragility of NiCl2 treated cells. NiCl2 treatment caused severe morphological alterations with the conversion of normal discocytes to echinocytes. All changes were seen in a NiCl2 concentration-dependent manner. ConclusionNiCl2 generates cytotoxic ROS in human erythrocytes which cause oxidative damage that can decrease the oxygen carrying capacity of blood and also lead to anemia.

Organic matter from water treatment residuals stabilizes amorphous iron to maintain phosphorus adsorption by iron hydroxides

Functional materials enriched with amorphous iron are commonly used for environmental remediation. However, their performance is often susceptible to aging and reductive dissolution effects. Amorphous iron in drinking water treatment residuals (DWTRs) primarily exists in organic matter-bound forms, possessing a stable phosphorus adsorption capability. In this study, in-depth investigations were conducted to evaluate the effect of organic matter extracted from DWTRs on amorphous iron stability in iron hydroxides by using incubation tests for 180 days. The results showed that organic matter from different DWTRs exhibited similar FTIR and XPS patterns; whereas, the solid-state carbon-13 NMR analysis and the carbon/nitrogen atom ratios indicated variations in structures and origins. Notably, organic matter addition increased the 0.01 and 0.005 M-oxalic acid-ammonium oxalate extractable iron, especially the later one which was greater than the control by approximately 24 times, inhibiting iron aging in iron hydroxides. The addition also promoted the transformation of iron from acid-soluble and reducible to oxidizable and non-European Community Bureau of Reference method-extractable forms, reducing the iron release potential. This effect was intensified when organic matter contained relatively low levels of carboxylic carbon and nitrogen/oxygen-alkyl carbon while high levels of carbon=oxygen/ketone carbon. The inhibited iron aging further led to stronger phosphorus adsorption capabilities of iron hydroxides, and the reduced iron release potential caused the adsorbed phosphorus to exist in more stable forms. Therefore, organic matter from DWTRs stabilized amorphous iron to maintain phosphorus adsorption capabilities of iron hydroxides. These mechanisms show potential for application in the development of iron-based materials.

Effects of phenolic acid analogs on the structure, iron oxidation/iron release, and stability of phytoferritin

Ferritin is a universal macromolecule protein that stores iron and regulates iron oxidative deposition and release. The physicochemical properties of ferritin can be affected by coexisting bioactive substances. This study investigated the effects of two phenolic acid analogs (caffeic acid and tanshinol) on the physicochemical properties of soybean ferritin. The results indicated that Fe(III) interacted with caffeic acid or tanshinol to form phenolic acid-Fe(III) complexes, and interacted with ferritin to form a ferritin-phenolic acid-Fe(III) complex with hydrogen bonds, which affected the ferritin structure of the complexes to a different extent due to their different structures. Caffeic acid and tanshinol facilitated iron oxidative deposition and release by promoting the Fe(II)-oxidation reaction and increasing Fe(III)-release from ferritin, while caffeic acid exhibited a more pronounced effect. In addition, caffeic acid protected ferritin from degradation by free radicals during the release of iron. Caffeic acid displayed a higher Fe(II) chelating ability and a higher hydroxyl radical (•OH) scavenging ability owing to the conjugated structure compared to tanshinol. These findings elucidated the mechanism for the interaction among ferritin, iron, and polyphenols, and provide a theoretical basis for applying ferritin in protein-ligand interactions and iron supplementation of food.

Non-alcoholic fatty liver disease as a risk factor for anemia of chronic inflammation (experimental research)

The aim of the study. In recent years, non-alcoholic fatty liver disease (NAFLD) has been considered a hepatic manifestation of the metabolic syndrome. The main consequence of NAFLD is chronic hepatic inflammation, which leads to dyslipidemia, inflammation, increased oxidative stress, and endothelial dysfunction. Immune activation in response to interaction with agents of a metabolic nature induces the release of pro-inflammatory cytokines in the liver, which subsequently cause iron сhomeostasis disorder. This leads to a frequent association of NAFLD with anemia of various etiology. In this regard, we considered it important to assess the severity of the systemic inflammatory response in NAFLD in the experiment in order to -diagnose anemia of chronic inflammation.Materials and methods. The study was carried out on 26 male Wistar rats, which were divided into control and experimental groups. In animals of the experimental group, NAFLD was modeled according to the generally accepted method. In order to assess metabolic disorders, we determined the main biochemical parameters, a complete blood count with the calculation of erythrocyte indices, the concentration of the main pro-inflammatory cytokines – interleukin (IL) 1, IL-6. Results. In laboratory rats with NAFLD, a statistically significant increase of intrahepatic enzymes in blood serum was found. The state of the erythrocyte lineage of hematopoiesis in the experimental group progressively worsened and caused the development of anemic syndrome. Synchronously, a statistically significant increase in serum levels of IL-1, IL-6 was recorded, which confirms the correlation of NAFLD with anemia of chronic inflammation.Conclusions. A high concentration of IL-1, IL-6 cytokines in NAFLD inhibits iron absorption in the duodenum, leads to the activation of macrophages, blocking the release of iron processed from aging erythrocytes into plasma. Further study of the mechanisms of anemia in NAFLD provides important therapeutic targets in the treatment of both NAFLD and its comorbidities.

Stabilization of Iron (0) in plasma treated semi porous polylactic acid based particles for in situ groundwater remediation

This study aims at incorporating reactive zero valent iron (ZVI) nanoparticles into water dispersible, biodegradable polymeric particles acting as a slow release reservoir of ZVI for targeting groundwater contaminants in situ. In order to accomplish the goal, three simple steps were adopted such as: 1) electrojetting of PLA (polylactic acid) with FeCl3 (∼17 wt%) to yield ∼700 nm sized monodisperse spherical particles (PLA_FeCl3) 2) surface modification of PLA_FeCl3 particles using oxygen plasma to enhance surface hydrophilicity and porosity (∼ 75%) 3) reduction of plasma treated PLA_FeCl3 particles in presence of NaBH4 to produce ZVI (size: 20–50 nm) entrapped PLA particles (PLA_ZVI) with high encapsulation efficiency of iron (∼85%). The plasma treated semi-porous PLA_ZVI particles exhibited slow and sustain release of iron (∼90% in ∼100 hrs) that were further employed to completely decontaminate both methyl orange (hydrophilic dye) and trichloroethylene (hydrophobic waste). Interestingly, the plasma treated particles were recyclable up to fourth batch, whereas the non-plasma treated one hardly show any recyclability due to burst release of surface entrapped iron from the latter. Moreover, the plasma treated hydrophilic particles provided stable dispersion (96 hrs) and prolonged reactivity (∼10 days in sand column) in water as opposed to non-plasma treated particles displaying 1 min dispersion stability in water. As a result, the plasma treated particles displayed smooth transportability through sand column (>80%) with negligible attachment efficiency (α = 1.1) onto sand particles. These attributes make them a potential alternative to bare ZVI (transportability <20%) for targeting hazardous pollutants by injecting them in groundwater.

Utility considerations in developing a galvanized iron water pipe management plan

AbstractGalvanized iron pipe (GIP) was once widely installed in publicly and privately owned potable water systems. This antiquated plumbing material can cause water discoloration from iron release, head loss resulting from corrosion scale buildup, and occasional problems with lead (Pb) release to drinking water. In this work, a GIP management framework for utilities is formulated via a literature review and several case studies. The GIP management plan is intended to guide water systems with understanding and addressing GIP issues while considering consumer expectations, corrosion control challenges, variable performance, and associated cost–benefit analysis for corrective actions.

Effect of Iron Salt on Slow Fertilization Through Soy Protein-Based Matrices

Due to the increase in horticultural production intensive techniques are needed. These techniques generate soil degradation, since the natural recovery time between crops is insufficient. The usual way to solve this problem is the use of fertilizers, as they are effective in the short time available. Conventional fertilizers are highly soluble salts, allowing their absorption by plant roots. However, they are dumped on the soils in more quantity than plants need, thus, the excess of unassimilated nutrients contaminates both the soil and groundwater. The main objective of this work was to develop and evaluate an alternative to conventional fertilizers, creating slow-release matrices from a protein by-product to which iron was incorporated. To carry out a more complete study, iron was incorporated in concentrations of 2.5, 5.0 and 10 wt%, using two different salts: iron(II) sulfate heptahydrate (FeSO4·7H2O) and iron chelated with N,N′-ethylenediamine-bis (2-hydroxyphenyl) acetic acid (Fe-EDDHA). Several tests were performed to compare their mechanical properties, micronutrient release profile, water absorption capacity and biodegradability, as well as their final effectiveness in crops. The protein-based matrices with both salts incorporated presented good mechanical properties. However, Fe-EDDHA matrices had a greater water absorption capacity, while FeSO4·7H2O matrices were more efficient in their final application in plants and had a longer biodegradation time. In conclusion, protein-based matrices present a high potential for the slow release of iron, thereby improving crop properties.

Vanillin attenuates CdCl2-induced cytotoxicity in isolated human erythrocytes

Cadmium is a toxic heavy metal with no physiological role in the human body. Cadmium has high mobility due to its widespread industrial use, with no safe and effective therapeutic management. Cadmium toxicity manifests by increasing oxidative stress in target cells. We have explored the potential role of vanillin, a plant phenolic aldehyde and antioxidant, in mitigating cadmium chloride (CdCl2) induced hemotoxicity using isolated human erythrocytes. CdCl2 was added to erythrocytes, in the absence and presence of vanillin. Incubation of erythrocytes with CdCl2 alone inhibited methemoglobin reductase and enhanced methemoglobin level. Heme degradation and release of free iron (Fe2+), along with protein and membrane lipid oxidation, were also increased. A CdCl2-induced enhancement in reactive oxygen and nitrogen species was also seen, lowering the overall antioxidant power of cells. However, pre-incubation of erythrocytes with vanillin resulted in significant decreased generation of reactive species and prevented heme degradation and heme oxidation. Vanillin augmented the erythrocyte antioxidant capacity and reinstated the activities of major antioxidant, plasma membrane-bound and glucose metabolism enzymes. Scanning electron microscopy showed that CdCl2 treatment led to the formation of echinocytes which was prevented by vanillin. In all cases, no harmful effects of vanillin alone were seen. Thus, vanillin alleviates the toxicity of cadmium and can be potentially employed as a chemoprotectant against the damaging effects of this heavy metal.

Encapsulation of atomized erythrocytes in liposomes as source of heme iron for oral supplementation strategies

AbstractThis work aimed to develop and characterize liposomes of atomized bovine erythrocytes (ABE‐liposomes) for potential use as a heme iron supplement or to fortify food with heme iron. Soy lecithin (SL) and Tween 80 (T80) were chosen to prepare empty liposomes (8 types), and ABE‐liposomes (16 types) by a rotary‐evaporated film method. Variables of interest for our study were: ABE concentration, proportion of SL:T80 and ultrasonic bath time. ABE‐liposomes were characterized according to appearance, color, morphology, Fourier transform infrared spectroscopy (FTIR), size, zeta potential, total iron content, encapsulation efficiency (EE) and in vitro iron release under gastrointestinal conditions. ABE‐liposomes presented a brown color and spherical shape. Hydrogen bridges were the main interactions in ABE‐liposomes. Their size ranged from 379 to 964 nm, the zeta potential from −56 to −74 mV, the iron concentration range was 0.8–9.0 mg/100 mL, and EE ranged from 29% to 48%. Ultrasonic bath time was the most important variable on the reduction of ABE‐liposomes' size and EE. Under in vitro gastrointestinal conditions, iron release from ABE‐liposomes occurred mainly at the intestinal level. In conclusion, ABE‐liposomes were effectively developed, which could become a complement for supplementation or food fortification strategies with nonheme for the prevention of iron deficiency anemia.Practical ApplicationsIn this study atomized bovine erythrocytes (ABE)‐liposomes were developed, due to the: (1) lack of supplements or products to fortify foods based on heme iron, (2) higher bioavailability of heme iron than nonheme iron, especially when working with ABE, and (3) ABE is a low value‐added product that is generated in slaughter plants and in turn is an excellent source of underutilized heme iron. In this study it was possible to develop ABE‐liposomes, where ABE was encapsulated inside liposomes, obtaining a product that could be used as a complement in iron supplementation strategies or food fortification to prevent or treat iron deficiency or iron deficiency anemia, especially in developing countries that have low consumption of heme iron.

Contribution of the Fenton reaction to the degradation of carbon nanotubes by enzymes

The widespread use of carbon nanotubes (CNTs) has raised concerns about the human health and ecological effects of CNTs released into the environment. Bacteria play an important role in bioremediation and waste treatment, and their enzymes are mostly responsible for the degradation of contaminants. However, there are still only a few reports about the bacterial degradation of CNTs, and evidence showing the involvement of bacterial enzymes in CNT degradation with their mechanisms has never been reported. The purpose of this study is to clarify whether CNTs can be degraded by bacterial enzymes. In this study, the degradation of oxidized (carboxylated) single-walled CNTs (O-SWCNTs) by mt2DyP, a dye-decolorizing peroxidase of Pseudomonas putida mt-2, a common soil bacterium, was investigated. After incubation of O-SWCNTs with recombinant mt2DyP and its substrate H2O2 for 30 d, the optical absorbance and Raman spectra revealed the degradation of O-SWCNTs. However, inactivation of the enzyme was observed within 60 min of the start of incubation, suggesting that the degradation of O-SWCNTs occurred nonenzymatically. The inactivation of mt2DyP was accompanied by the release of iron, the active center metal, and degradation of O-SWCNTs was significantly inhibited in the presence of diethylenetriamine pentaacetic acid, a chelating agent, indicating that O-SWCNTs were degraded by the Fenton reaction with iron released from mt2DyP and H2O2. The same phenomenon was observed with P450, which is also a heme enzyme. Furthermore, we investigated the contribution of the Fenton reaction to the O-SWCNT degradation by horseradish peroxidase (HRP), which was reported to enzymatically and rapidly degrade O-SWCNTs. Our results revealed that the degradation of O-SWCNTs in the presence of HRP is also mainly due to the Fenton reaction, with negligible enzymatic degradation. This contradicts the report showing enzymatic degradation of O-SWCNTs by HRP but supports the subsequent report quantitatively showing very slow transformation of O-SWCNTs by HRP. The current results emphasize that the Fenton reaction, which has received little attention in CNT degradation by heme enzymes, must be taken into consideration and will contribute to the development of a simple disposal method for CNTs, utilizing the Fenton reaction with bacteria/bacterial enzymes and H2O2.

The Role of Fractalkine in the Regulation of Endometrial Iron Metabolism in Iron Deficiency.

Iron is a crucial element in the human body. Endometrial iron metabolism is implicated in endometrium receptivity and embryo implantation. Disturbances of the maternal as well as the endometrial iron homeostasis, such as iron deficiency, can contribute to the reduced development of the fetus and could cause an increased risk of adverse pregnancy outcomes. Fractalkine is a unique chemokine that plays a role in the communication between the mother and the fetus. It has been demonstrated that FKN is involved in the development of endometrial receptivity and embryo implantation, and it functions as a regulator of iron metabolism. In the present study, we examined the effect of FKN on the iron metabolism of HEC-1A endometrial cells in a state of iron deficiency mediated by desferrioxamine treatment. Based on the findings, FKN enhances the expression of iron metabolism-related genes in iron deficiency and modifies the iron uptake via transferrin receptor 1 and divalent metal transporter-1, and iron release via ferroportin. FKN can activate the release of iron from heme-containing proteins by elevating the level of heme oxygenase-1, contributing to the redistribution of intracellular iron content. It was revealed that the endometrium cells express both mitoferrin-1 and 2 and that their levels are not dependent on the iron availability of the cells. FKN may also contribute to maintaining mitochondrial iron homeostasis. FKN can improve the deteriorating effect of iron deficiency in HEC-1A endometrium cells, which may contribute to the development of receptivity and/or provide iron delivery towards the embryo.

In-situ synthesis of ionic liquid-based-carbon quantum dots as fluorescence probe for hemoglobin detection

Carbon quantum dots (CQDs) have emerged as a potential fluorescent probe in bio/analytical chemistry in the present decade. The optical characteristics of CQDs may be tuned by their functional groups, which can also be used to selectively produce stable bonds with target molecules. Along with them, ionic liquids (ILs) are now demonstrating their important relevance in the field of pharmaceuticals for the creation of potent therapeutics. In the article, we have discussed the use of high fluorescent ILs-decorated-CQDs (CQDs-IM@OTf) as a straightforward and quick-acting fluorescence probe for sensitive and precise hemoglobin (Hb) determination with minimum detectability of 6.7 nM. The proposed mechanism behind this involves static mode of quenching which leads to the formation of a ground state complex [CQDs-IM@OTf-Hb complex] between the Hb protein and the drug. Despite the fact that Hb can quench the fluorescence of CQDs due to the inner filter effect (IFE) of the protein, which effects both the excitation and emission spectra of the CQDs, the addition of H2O2 improved the sensitivity of Hb detection. The present assay predicated on Hb interaction with H2O2, which produces reactive oxygen species such as hydroxyl (OH.) and superoxide (O2.−) radicals under heme degradation and/or iron release from Hb. The subsequent reaction of hydroxyl radicals with CQDs, which acts as a strong oxidising agent, causes a high fluorescence quenching. The designed fluorescence probe was used to measure Hb in the concentration range of 3–90 nM with a precise detection limit of 0.33 nM. The quantification of hemoglobin (Hb) in diluted human blood samples is done using this observation.

Apo- and holo-transferrin differentially interact with hephaestin and ferroportin in a novel mechanism of cellular iron release regulation

BackgroundApo- (iron free) and holo- (iron bound) transferrin (Tf) participate in precise regulation of brain iron uptake at endothelial cells of the blood–brain barrier. Apo-Tf indicates an iron-deficient environment and stimulates iron release, while holo-Tf indicates an iron sufficient environment and suppresses additional iron release. Free iron is exported through ferroportin, with hephaestin as an aid to the process. Until now, the molecular mechanisms of apo- and holo-Tf influence on iron release was largely unknown.MethodsHere we use a variety of cell culture techniques, including co-immunoprecipitation and proximity ligation assay, in iPSC-derived endothelial cells and HEK 293 cells to investigate the mechanism by which apo- and holo-Tf influence cellular iron release. Given the established role of hepcidin in regulating cellular iron release, we further explored the relationship of hepcidin to transferrin in this model.ResultsWe demonstrate that holo-Tf induces the internalization of ferroportin through the established ferroportin degradation pathway. Furthermore, holo-Tf directly interacts with ferroportin, whereas apo-Tf directly interacts with hephaestin. Only pathophysiological levels of hepcidin disrupt the interaction between holo-Tf and ferroportin, but similar hepcidin levels are unable to interfere with the interaction between apo-Tf and hephaestin. The disruption of the holo-Tf and ferroportin interaction by hepcidin is due to hepcidin’s ability to more rapidly internalize ferroportin compared to holo-Tf.ConclusionsThese novel findings provide a molecular mechanism for apo- and holo-Tf regulation of iron release from endothelial cells. They further demonstrate how hepcidin impacts these protein–protein interactions, and offer a model for how holo-Tf and hepcidin cooperate to suppress iron release. These results expand on our previous reports on mechanisms mediating regulation of brain iron uptake to provide a more thorough understanding of the regulatory mechanisms mediating cellular iron release in general.