Expressions of iron transport related proteins in the spinal cord of amyotrophic lateral sclerosis transgenic mice / 解剖学报

Objective To investigate the relationship between the expressions of iron transport related proteins and the dysregulation of iron homeostasis in the spinal cord of amyotrophic lateral sclerosis (ALS) transgenic mice. Methods The hSOD1

Hepcidina: la llave del metabolismo del hierro / Hepcidin: the key of iron metabolism / Hepcidina: a chave do metabolismo do ferro

En las últimas décadas se ha avanzado en el conocimiento de la regulación del metabolismo del Hierro (Fe). La Hepcidina (Hp), producida por los hepatocitos, regula la absorción de hierro desde el tubo digestivo y la liberación desde los depósitos del sistema macrofágico y del hígado. En caso de deficiencia de Fe, la Hp está disminuida entregando Fe a la transferrina (Tf). El aumento de Fe y de las citoquinas de la inflamación estimulan la producción de Hp. El ejecutor de la Hp es la Ferroportina (FP), único exportador de Fe. Hay reguladores naturales de la Hp, como la Matriptasa 2. Las mutaciones que limitan su expresión inducen dificultades en la disponibilidad de Fe (IRIDA, sobrecarga de Fe). En los últimos años se ha identificado la Eritroferrona, producida por los eritroblastos activos en la eritropoyesis. Inhibe la síntesis de Hp, permitiendo la liberación del hierro de los depósitos y su absorción por el tubo digestivo, para facilitar la disponibilidad de Fe para la eritropoyesis. Aún no está definido cómo se podrán utilizar estos elementos en el campo diagnóstico, su estandarización y su aplicación terapéutica, pero es probable que resulten de gran utilidad.

In the last decades, a lot of progress has been made on the knowledge of iron (Fe) metabolism regulation. Hepcidin (Hp) is produced by hepatocytes and it regulates the iron absorption from the duodenum and the liberation from macrophages and from the liver. When there is iron deficiency, Hp, which delivers iron to transferrin (Tf), is low. Iron overload and inflammation cytokines stimulate Hp production. The Hp natural executor is Ferroportin (FP), which is the only iron exporter from the cells. One of the natural regulators of Hp is Matriptasa 2, which down regulates Hp. Mutations that limit their expression induce iron overload and anemia (IRIDA). In the last few years, Erythroferrone (ERFE) was discovered. ERFE is produced by active erythroblasts: it inhibits Hp synthesis, allowing the iron liberation from deposits and its duodenal absorption, and also the iron release from macrophages facilitating the erythroid production. The erythroblastic activity, even ineffective, acts as a stimulus of ERFE synthesis. Until now, it has not been defined yethow these different variables could be used for diagnosis, its standardization, or for therapeutic applications, but it is highly probable that they will improve our knowledge and managements kills in this field.

Nas últimas décadas háavanços no conhecimento da regulação do metabolismo do Ferro (Fe). A Hepcidina (Hp), produzida pelos hepatócitos, regula a absorção do ferro desde o tubo digestivo e a liberação desde os depósitos do sistema macrofágico e do fígado. Em caso de deficiência de Fe, a Hp está diminuída entregando Fe à transferrina (Tf). O aumento de Fe e as citoquinas da inflamação estimulam a produção de Hp. O executor da Hp é a Ferroportina (Fp), único exportador de Fe. Há reguladores naturais da Hp, como a Matriptase 2. As mutações que limitam sua expressão induzem dificultades na disponibilidade de Fe (IRIDA, sobrecarga de Fe). Nos últimos anos se identificou que a Eritroferrona, produzida pelos eritroblastosativos na eritropoiese inibe a síntese de Hp, permitindo a liberação de ferro dos depósitos e a absorção pelo tubo digestivo, para facilitar a disponibilidade de Fe para a eritropoiese. Ain da não sedefiniu como poderãoser utilizadosestes elementos no campo diagnóstico, sua padronização e sua aplicação terapêutica, mas é provável que sejam de grande utilidade.

The establishment of atherosclerotic cell model and the preliminary study of intracellular iron metabolism disorder / 介入放射学杂志

Objective To establish the atherosclerosis (AS) cell model,to study the relationship between the iron metabolism and AS,and to explore the molecular mechanisms of iron metabolism disorders within the macrophages in AS plaques so as to provide theoretical basis for clinical intervention of iron metabolism and for the prevention and treatment of AS.Methods RAW264.3 cells were used to prepare foam cells through oxidized low density lipoprotein (ox-LDL) induced oxidation.In order to verify the foam cells,oil red staining and enzyme-linked immunosorbent were employed to assay the total lipids and free lipids (including total cholesterol and free cholesterol) in the foam cells.Western blotting was adopted to test the levels of iron metabolism-associated ferritin (FT) and ferroportin1 (FPN1);immunohistochemistry and immunofluorescence methods were used to determine and locate the expressions of FPN1 in foam cells.Results Large amounts of red lipid granules could be seen within the cytoplasm of ox-LDL-induced foam cells,and a great quantity of lipid fused into the form of large oil droplets,which was consistent with the morphological characteristics of foam cells.Massive lipid was accumulated in the foam cells,and the proportion of cholesterol ester (CE) in the foam cells was significantly higher than that in the normal cells (P＜ 0.05).Compared with the normal control group,FT content in the foam cells was obviously higher than that in the normal cells;the content of FPN1 was increased,and the increased content of FPN1 mainly existed in cytoplasm.Conclusion In the foam cells the iron metabolism is disordered and a great quantity of FPN1 is accumulated in cytoplasm.The non-cell-membrane localization of FPN1 can prevent iron from being effectively discharged from macrophages and can increase the accumulation of iron in foam cells,which may aggravate the formation and development of AS plaques.

Regulación del metabolismo del hierro: dos sistemas, un mismo objetivo / Iron metabolism regulation: two systems, one goal

La existencia humana está indisolublemente unida al hierro, que es parte de una amplia variedad de enzimas claves como catalasas, aconitasas, ribonucleótido reductasa, peroxidasas y citocromos, que explotan la flexibilidad de su química redox para ejecutar un elevado número de reacciones esenciales para la vida. El cuerpo humano ha evolucionado para conservar el hierro en diferentes formas, incluido su reciclaje después de la ruptura de los eritrocitos y la retención en ausencia de un mecanismo de excreción. El metabolismo del hierro está balanceado por dos sistemas regulatorios: uno sistémico basado en la hormona hepcidina y la proteína exportadora ferroportina, y el otro que controla el metabolismo celular través de las proteínas reguladoras de hierro (IRP) que se unen a los elementos de respuesta al hierro (IRE) de los ARNm regulados. Estos sistemas funcionan de modo coordinado lo que evita, tanto la deficiencia como el exceso del mineral(AU)

Human existence is indissolubly linked to iron, which is part of a wide variety of key enzymes such as catalase, aconitases, ribonucleotide reductase, peroxidases and cytochromes, exploiting the flexibility of its redox chemistry to run a large number of reactions essential for life. Human body has evolved to keep iron in different forms, including recycling after rupture of erythrocytes and the retention without excretion mechanism. Iron metabolism is balanced by two regulatory systems: one based on systemic hormone hepcidin protein export and ferroportin, and the other, which controls cell metabolism through the iron regulatory protein (IRP) binding to the mRNAs regulated iron regulatory elements (IRE). These systems work in a coordinated manner avoiding both deficiency and excess(AU)

Iron dysregulation in beta-thalassemia

Iron deficiency anemia and iron overload conditions affect more than one billion people worldwide. Iron homeostasis involves the regulation of cells that export iron into the plasma and cells that utilize or store iron. The cellular iron balance in humans is primarily mediated by the hepcidin–ferroportin axis. Ferroportin is the sole cellular iron export protein, and its expression is regulated transcriptionally, post-transcriptionally and post-translationally. Hepcidin, a hormone produced by liver cells, post-translationally regulates ferroportin expression on iron exporting cells by binding with ferroportin and promoting its internalization by endocytosis and subsequent degradation by lysosomes. Dysregulation of iron homeostasis leading to iron deposition in vital organs is the main cause of death in beta-thalassemia patients. Beta-thalassemia patients show marked hepcidin suppression, ineffective erythropoiesis, anemia and iron overload. Beta-thalassemia is common in the Mediterranean region, Southeast Asia and the Indian subcontinent, and the focus of this review is to provide an update on the factors mediating hepcidin related iron dysregulation in beta-thalassemia disease. Understanding this process may pave the way for new treatments to ameliorate iron overloading and improve the long term prognosis of these patients.

Iron dysregulation in beta-thalassemia

Iron deficiency anemia and iron overload conditions affect more than one billion people worldwide. Iron homeostasis involves the regulation of cells that export iron into the plasma and cells that utilize or store iron. The cellular iron balance in humans is primarily mediated by the hepcidin-ferroportin axis. Ferroportin is the sole cellular iron export protein, and its expression is regulated transcriptionally, post-transcriptionally and post-translationally. Hepcidin, a hormone produced by liver cells, post-translationally regulates ferroportin expression on iron exporting cells by binding with ferroportin and promoting its internalization by endocytosis and subsequent degradation by lysosomes. Dysregulation of iron homeostasis leading to iron deposition in vital organs is the main cause of death in beta-thalassemia patients. Beta-thalassemia patients show marked hepcidin suppression, ineffective erythropoiesis, anemia and iron overload. Beta-thalassemia is common in the Mediterranean region, Southeast Asia and the Indian subcontinent, and the focus of this review is to provide an update on the factors mediating hepcidin related iron dysregulation in beta-thalassemia disease. Understanding this process may pave the way for new treatments to ameliorate iron overloading and improve the long term prognosis of these patients.

Effects of obesity on the expression of hepcidin, lipocalin-2 and ferroportin-1 related with iron metabolism of mice’ s liver / 中国比较医学杂志

Objective We established the animal models of obesity induced by high-fat diet, in order to study the mRNA and protein expression of regulation molecules related with iron metabolism about hepcidin, lipocalin-2 ( LCN2 ) , ferroportin-1 (FPN1) in obese mice’ s liver and the molecular regulation mechanism.Methods C57BL/6J (4 ~6 weeks) mice were randomly divided into control group and obesity model group, each group of ten.The obesity group were fed with a high-fat diet and the control group were given the normal diet for lasting 15 weeks.After we successfully established the obesity animal model, the expression level of hepcidin, LCN2 and FPN1 mRNA in the liver were measured by Real-time fluorescent quantitative PCR method and the protein expression level of LCN2 and FPN1 were measured by Western-Blot.Results Compared with the control group, the expression level of hepcidin mRNA in the liver was increased in obesity group (P 0.05).Conclusion Obesity can increase the expression of hepcidin mRNA, however, there was no significantly effect on the expression of LCN2, FPN1.So, we can’t think that obesity can affect the expression of LCN2 and FPN1, lead to the ability of cells uptake and release iron abnormal, then appear iron metabolism disorders.As a result, leading to iron deficiency.Maybe obesity can affect other regulatory molecules related with iron metabolism through up-regulation the expression of Hepcidin or the more complex regulatory mechanisms.We still need further experimental research and exploration.This research also provides the basis of theoretical and experimental for the further study the effects of obesity on the expression of regulation molecules related with iron metabolism in obesity mice’ s liver and the mechanism of iron deficiency.

Effects of developmental iron deficiency and post-weaning iron repletion on the levels of iron transporter proteins in rats

BACKGROUND/OBJECTIVES: Iron deficiency in early life is associated with developmental problems, which may persist until later in life. The question of whether iron repletion after developmental iron deficiency could restore iron homeostasis is not well characterized. In the present study, we investigated the changes of iron transporters after iron depletion during the gestational-neonatal period and iron repletion during the post-weaning period. MATERIALS/METHODS: Pregnant rats were provided iron-deficient (< 6 ppm Fe) or control (36 ppm Fe) diets from gestational day 2. At weaning, pups from iron-deficient dams were fed either iron-deficient (ID group) or control (IDR group) diets for 4 week. Pups from control dams were continued to be fed with the control diet throughout the study period (CON). RESULTS: Compared to the CON, ID rats had significantly lower hemoglobin and hematocrits in the blood and significantly lower tissue iron in the liver and spleen. Hepatic hepcidin and BMP6 mRNA levels were also strongly down-regulated in the ID group. Developmental iron deficiency significantly increased iron transporters divalent metal transporter 1 (DMT1) and ferroportin (FPN) in the duodenum, but decreased DMT1 in the liver. Dietary iron repletion restored the levels of hemoglobin and hematocrit to a normal range, but the tissue iron levels and hepatic hepcidin mRNA levels were significantly lower than those in the CON group. Both FPN and DMT1 protein levels in the liver and in the duodenum were not different between the IDR and the CON. By contrast, DMT1 in the spleen was significantly lower in the IDR, compared to the CON. The splenic FPN was also decreased in the IDR more than in the CON, although the difference did not reach statistical significance. CONCLUSIONS: Our findings demonstrate that iron transporter proteins in the duodenum, liver and spleen are differentially regulated during developmental iron deficiency. Also, post-weaning iron repletion efficiently restores iron transporters in the duodenum and the liver but not in the spleen, which suggests that early-life iron deficiency may cause long term abnormalities in iron recycling from the spleen.

Effect of lipopolysaccharide on the iron metabolism in macrophages / 解剖学报

Objective To study the effect of lipopolysaccharide ( LPS ) on the activity of primary cultured macrophages and the distribution of divalent metal transporter 1 ( DMT1 ) and ferroportin 1 ( FPN1 ) .Methods Primary cell culture , MTT chromotest , cytochemistry chromotest and cell immunofluorescence techniques were used in this work . Results DMT1 was mainly distributed in the cytoplasm , which illuminates that DMT1 mediates the macrophage intracellular transit of iron from phagolysosome to cytoplasm .FPN1 was distributed in the cytoplasm and membrane , and the cytoplasm was the main site of FPN 1 distribution in macrophages .Conclusion Iron liberation from heme inside the phagolysosome occurs after erythrophagocytosis and it is possible that FPN 1 mediates intracellular transit of iron released by heme catabolism .The study found that LPS promoted the cell growth and this effect was reached to the peak in the 10 -5μg/L LPS group, but the cell growth was blocked with the increase of LPS concentration .

Effect on expression of macrophages ferroportin and ferritin in mouse alveolar macrophages by mycobacterium tuberculosis / 中国免疫学杂志

Objective:To discuss the change of ferritin ( Fn) and ferroportin expression quantity and time-related feature in the alveolar macrophages of mice , infected with different virulence of Mycobacterium Tuberculosis infected .Methods:The prepared bacte-ria of H37Rv or BCG were injected intravenously into the mice tails .On the day 1, 3, 5, 7, 9, 11, 13 and 15, the lavage fluids were collected and the alveolar macrophages were obtained from each group of mice .The expression of FPN and Fn were detected with ELISA and /or Western blot analysis .Results:The expression of Fn in the group of either H 37Rv or BCG infected mice was decreased on the day 7, 9 and 11, and was lowest on the day 7, which showed significantly statistical difference compared to that on the other days (P<0.05).The expression of FNP in the infected mouse macrophage was decreased gradually , which was obvious on the day 5. The expression levels reached to the lowest on the day 7 and 9.The expression was much lower than that in the negative control group (P<0.05).Conclusion:The expression of Fn and FPN in macrophages isolated from lungs of mice infected with Mycobacterium tu -berculosis H37Rv or BCG become decreased , and there is no difference between these two infected mouse groups .

Effect of obesity on the expression of DMT1 and FPN1 in the duodenal in mice / 中国比较医学杂志

Objective To study the expression of divalent metal transporter 1(DMT1)and ferroportin 1(FPN1)in obese mice’ s duodenal epithelium and investigate the mechanism of the effect of obesity on iron absorption in mice. Methods C57BL/6J mice were randomly divided into control group and obesity model group, each group of 6, To establish obese mice model by having a high-fat diet and the control group were fed with a normal diet for 12 weeks.After completion of modeling, The level of DMT1 and FPN1 mRNA expression in the duodenum were measured by real-time fluorescent quantitative PCR( Real-time PCR) method, the protein expression of FPN1 was measured by Western-Blot. Results Compared with the control group, the level of DMT1、FPN1 mRNA and FPN1 protein expression in the duodenum were decreased significantly in obese mice ( P <0.05 ) .Conclusion Obesity can decrease the expression levels of DMT1、FPN1 mRNA and FPN1 protein and induce iron deficiency,in order to provide experimental and theoretical basis for studying the mechanism of iron deficiency caused by obesity further.

Role of hepcidin in the pathophysiology and diagnosis of anemia

This review summarizes the central role of hepcidin in the iron homeostasis mechanism, the molecular mechanism that can alter hepcidin expression, the relationship between hepcidin and erythropoiesis, and the pathogenetic role of hepcidin in different types of anemia. In addition, the usefulness of hepcidin dosage is highlighted, including the problems associated with analytical methods currently used as well as the measures of its molecular isoforms. Considering the central role of hepcidin in iron arrangement, it is reasonable to ponder its therapeutic use mainly in cases of iron overload. Further clinical trials are required before implementation.

Role of hepcidin in the pathophysiology and diagnosis of anemia

This review summarizes the central role of hepcidin in the iron homeostasis mechanism, the molecular mechanism that can alter hepcidin expression, the relationship between hepcidin and erythropoiesis, and the pathogenetic role of hepcidin in different types of anemia. In addition, the usefulness of hepcidin dosage is highlighted, including the problems associated with analytical methods currently used as well as the measures of its molecular isoforms. Considering the central role of hepcidin in iron arrangement, it is reasonable to ponder its therapeutic use mainly in cases of iron overload. Further clinical trials are required before implementation.

Quantitative study of iron metabolism-related genes expression in rat / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the multiple iron metabolism-related genes expression, its regulation by iron and the expression correlation among the genes in rat tissues.</p><p><b>METHODS</b>Two groups (n=30) of Sprague-Dawley female weanling rats were fed with a control diet and an iron deficient diet respectively for 4 weeks. All rats were then sacrificed, and blood and tissue samples were collected. The routine blood examination was performed with a veterinary automatic blood cell analyzer. Elemental iron levels in liver, spleen and serum were determined by atomic absorption spectrophotometry. The mRNA expression of genes was detected by real-time fluorescence quantitative PCR.</p><p><b>RESULTS</b>After 4 weeks, the hemoglobin (Hb) level and red blood cell (RBC) count were significantly lower in the iron deficient group compared with those in the control group. The iron levels in liver, spleen and serum in the iron deficient group were significantly lower than those in the control group. In reference to small intestine, the relative expression of each iron-related gene varied in the different tissues. Under the iron deficiency, the expression of these genes changed in a tissue-specific manner. The expression of most of the genes significantly correlated in intestine, spleen and lung, but few correlated in liver, heart and kidney.</p><p><b>CONCLUSION</b>Findings from our study provides new understandings about the relative expression, regulation by iron and correlation among the mRNA expressions of transferrin receptors 1 and 2, divalent metal transporter 1, ferritin, iron regulation proteins 1 and 2, hereditary hemochromatosis protein, hepcidin, ferroportin 1 and hephaestin in intestine, liver, spleen, kidney, heart, and lung of rat.</p>

Regulación de la hepcidina y homeostasis del hierro: avances y perspectivas / Regulation of hepcidin and iron homeostasis: progress and prospects

El estudio de los desórdenes genéticos del metabolismo del hierro, la identificación de sus transportadores y el descubrimiento de la hepcidina, hormona reguladora de la homeostasia del hierro, han contribuido grandemente a aumentar los conocimientos sobre este metabolismo y han cambiado sustancialmente la visión sobre las enfermedades relacionadas con alteraciones del metabolismo férrico. En la última década, no solo se han esclarecido elementos de la patogénesis de estas enfermedades, sino que ya se vislumbran aplicaciones terapéuticas de estos avances. Así, ya se habla de una nueva era basada en el tratamiento de los desórdenes de la homeostasia del hierro a través de la modulación de la hepcidina

The study of genetic disorders of iron metabolism, identification of transporters and the discovery of hepcidin- a hormone regulating iron homeostasis- have contributed greatly to increase awareness of this metabolism. Substantially, the vision on diseases related to disorders of iron metabolism has been changed. In the last decade, elements of the pathogenesis of these diseases have not only been clarified, but therapeutic applications of these advances are looming. Thus, there are expectations of a new era based on the treatment of iron homeostasis disorders through hepcidin modulation

Effects of lipopolysaccharide on mice iron metabolism related genes mRNA expression / 解剖学报

ObjectiveTo investigate the effects of lipopolysaccharide (LPS) on mRNA expression of iron metabolism related genes. Methods Ten male mice (2 months) were injected intraperitoneally with lipopolysaccharide(0.5 μg/g). After 6 hours, mice were sacrificed and then sera, liver and spleen were collected. The mice blood routine was measured. The serum iron and total iron binding capacity (TIBC) were determined with reagent kit. The quasi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed for mRNA of hepatic hepcidin(HP), ferroportin1(Fpn1), transferrin receptor 1(TfR1) and spleenic HP, Fpn1 and interleukin-6(IL-6). Results The serum iron and TIBC were reduced in mice injected LPS, which exhibited mild anemia(P＜0.05) . LPS can increase the expression of hepatic hepcidin and decrease Fpn1 and TfR1 in liver after LPS administration 6 hours(P＜0.05). In spleen, IL-6 was upregulated and Fpn1 downregulated(P＜0.05). Conclusion LPS can influence serum iron through regulating the mRNA expression of hepatic and spleenic iron metabolism related genes, such as HP, Fpn1 and TfR1.

Effect of Copper on the Regulation of Ferroportin-1 Gene Expression

Ferroportin-1 (FPN) is a transporter protein that is known to mediate iron export from macrophages. The purpose of this study was to investigate the effect of copper on the regulation of FPN gene expression in J774 mouse macrophage cells. J774 cells were treated with various concentrations of CuSO4 and RT-PCR analyses were performed to measure the steady-state levels of mRNAs for FPN and divalent metal transporter 1 (DMT1, an iron importer). Copper treatment significantly increased FPN mRNAs in a dose-dependent manner, but didn't change the levels of DMT1 mRNA. Experiments with transcriptional inhibitor actinomycin D (0.5 microgram/mL) revealed that copper treatment did not affect the half-life of FPN mRNAs in J774 cells. On the other hand, results from luciferase reporter assays showed that copper directly stimulated the promoter activity of FPN. In summary, our data showed copper induced FPN mRNA of macrophages via a transcriptional rather than post-transcriptional mechanisms.

Cadmium increases ferroportin-1 gene expression in J774 macrophage cells via the production of reactive oxygen species

Cadmium intoxication has been associated with the dysregulation of iron homeostasis. In the present study, we investigated the effect of cadmium on the expression of ferroportin 1 (FPN1), an important iron transporter protein that is involved in iron release from macrophages. When we incubated cadmium with J774 mouse macrophage cells, FPN1 mRNA levels were significantly increased in a dose- and time-dependent manner. Furthermore, the cadmium-induced FPN1 mRNA expression was associated with increased levels of FPN1 protein. On the other hand, cadmium-mediated FPN1 mRNA induction in J774 cells was completely blocked when cells were co-treated with a transcription inhibitor, acitomycin D. Also, cadmium directly stimulated the activity of the FPN1-promoter driven luciferase reporter, suggesting that the cadmium up-regulates FPN1 gene expression in a transcription-dependent manner. Finally, cadmium exposure to J774 macrophages increased intracellular reactive oxygen species (ROS) levels by ~ 2-fold, compared to untreated controls. When J774 cells were co-treated with antioxidant N-acetylcystein, the cadmium-induced FPN1 mRNA induction was significantly attenuated. In summary, the results of this study clearly demonstrated that cadmium increased FPN1 expression in macrophages through a mechanism that involves ROS production, and suggests another important interaction between iron and cadmium metabolism.

Effects of various metal ions on the gene expression of iron exporter ferroportin-1 in J774 macrophages

Macrophages play a key role in iron metabolism by recycling iron through erythrophagocytosis. Ferroportin-1 (FPN1) is a transporter protein that is known to mediate iron export from macrophages. Since divalent metals often interact with iron metabolism, we examined if divalent metals could regulate the expression of FPN1 in macrophages. J774 macrophage cells were treated with copper, manganese, zinc, or cobalt at 10, 50, or 100 microM for 16 to 24 h. Then, FPN1 mRNA and protein levels were determined by quantitative real-time PCR and Western blot analyses, respectively. In addition, effects of divalent metals on FPN1 promoter activity were examined by luciferase reporter assays. Results showed that copper significantly increased FPN1 mRNA levels in a dose-dependent manner. The copper-induced expression of FPN1 mRNA was associated with a corresponding increase in FPN1 protein levels. Also, copper directly stimulated the activity of FPN1 promoter-driven reporter construct. In contrast, manganese and zinc had no effect on the FPN1 gene expression in J774 cells. Interestingly, cobalt treatment in J774 cells decreased FPN1 protein levels without affecting FPN1 mRNA levels. In conclusion, our study results demonstrate that divalent metals differentially regulate FPN1 expression in macrophages and indicate a potential interaction of divalent metals with the FPN1-mediated iron export in macrophages.

The effect of burns on iron-related proteins in liver and spleen of different sex mice / 西安交通大学学报(医学版)

Objective To investigate the changes of iron-related proteins in different sex mice before and after burns.Methods The burn model in mice were prepared with 90 ℃ vapor.Both liver and spleen iron contents were measured by colorimetric method.Hepatic hepcidin and Fpn1 mRNA content were determined with RT-PCR.The Fpn1 protein was determined with Western blot.Results After burns,the content of spleen iron was increased and the expression of hepatic hepcidin was decreased in male mice,and at the same time the Fpn1 of liver and spleen was reduced.The content of iron homeostasis abnormality in female mice was less serious.Conclusion The change of iron-related proteins after burns may be one cause of iron homeostasis abnormality.The differences of iron-related protein expression in different sex after burns suggest that estrogen has a potentially protective function.