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1.
Adv Exp Med Biol ; 1173: 105-123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456207

RESUMO

Ischemic and hemorrhagic stroke are the common types of stroke that lead to brain injury neurological deficits and mortality. All forms of stroke remain a serious health issue, and there is little successful development of drugs for treating stroke. Incomplete understanding of stroke pathophysiology is considered the main barrier that limits this research progress. Besides mitochondria and free radical-producing enzymes, labile iron is an important contributor to oxidative stress. Although iron regulation and metabolism in cerebral stroke are not fully understood, much progress has been achieved in recent years. For example, hepcidin has recently been recognized as the principal regulator of systemic iron homeostasis and a bridge between inflammation and iron regulation. This review discusses recent research progress in iron pathophysiology following cerebral stroke, focusing molecular regulation of iron metabolism and potential treatment targets.


Assuntos
Ferro/metabolismo , Acidente Vascular Cerebral/patologia , Hepcidinas/metabolismo , Humanos , Estresse Oxidativo
3.
An Acad Bras Cienc ; 91(2): e20180286, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31090790

RESUMO

Investigation of hyperferritinemia in metabolic syndrome patients represents a diagnostic challenge, but it is essential for the identification of individuals with iron overload. Hepcidin negatively regulates iron absorption and release. An increase in hepcidin occurs when iron levels are sufficient or in inflammatory states, conditions often associated with hyperferritinemia. Hemochromatosis causes hyperferritinemia due to iron overload, but frequently has low hepcidin levels. Our aim was to evaluate biochemical and molecular parameters related to iron metabolism in patients with metabolic syndrome. We evaluated 94 patients with metabolic syndrome according to the International Diabetes Federation criteria in a cross-sectional study. Anthropometric data and diagnostic criteria for metabolic syndrome, iron dosage, ferritin, transferrin saturation, hepcidin, and the C282Y and H63D mutations in the HFE hemochromatosis gene were evaluated. Prevalence of hyperferritinemia in the study population was 27.7% and was higher in males (46.2%) than in females (14.5%). Increase in transferrin saturation correlated with mutations in the hemochromatosis gene. Hyperferritinemia was associated to transferrin saturation and hepcidin after logistic regression analysis. In conclusion, hyperferritinemia is a frequent finding in metabolic syndrome patients, most frequently in men; and hepcidin assessment can be useful for the investigation of ferritin increase in those subjects.


Assuntos
Ferritinas/metabolismo , Hepcidinas/metabolismo , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/etiologia , Síndrome Metabólica/complicações , Adolescente , Biomarcadores , Índice de Massa Corporal , Estudos Transversais , Feminino , Ferritinas/sangue , Hepcidinas/sangue , Humanos , Ferro/sangue , Sobrecarga de Ferro/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Fatores Sexuais
4.
Oxid Med Cell Longev ; 2019: 7623023, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049138

RESUMO

Iron homeostasis in the cardiac tissue as well as the involvement of the hepcidin-ferroportin (HAMP-FPN) axis in this process and in cardiac functionality are not fully understood. Imbalance of iron homeostasis occurs in several cardiac diseases, including iron-overload cardiomyopathies such as Friedreich's ataxia (FRDA, OMIM no. 229300), a hereditary neurodegenerative disorder. Exploiting the induced pluripotent stem cells (iPSCs) technology and the iPSC capacity to differentiate into specific cell types, we derived cardiomyocytes of a FRDA patient and of a healthy control subject in order to study the cardiac iron homeostasis and the HAMP-FPN axis. Both CTR and FRDA iPSCs-derived cardiomyocytes express cardiac differentiation markers; in addition, FRDA cardiomyocytes maintain the FRDA-like phenotype. We found that FRDA cardiomyocytes show an increase in the protein expression of HAMP and FPN. Moreover, immunofluorescence analysis revealed for the first time an unexpected nuclear localization of FPN in both CTR and FRDA cardiomyocytes. However, the amount of the nuclear FPN was less in FRDA cardiomyocytes than in controls. These and other data suggest that iron handling and the HAMP-FPN axis regulation in FRDA cardiac cells are hampered and that FPN may have new, still not fully understood, functions. These findings underline the complexity of the cardiac iron homeostasis.


Assuntos
Cardiomiopatias/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Ataxia de Friedreich/metabolismo , Hepcidinas/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Ferro/metabolismo , Miócitos Cardíacos/metabolismo , Cardiomiopatias/patologia , Ataxia de Friedreich/patologia , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Miócitos Cardíacos/patologia
5.
Mediators Inflamm ; 2019: 5764061, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30936776

RESUMO

Purpose: Hepcidin is an acute-phase protein involved also in regulation of iron homeostasis. The aim of the study was to prospectively assess for the first time the hepcidinEL concentration in patients with subacute thyroiditis (SAT), to identify biochemical determinants of hepcidinEL concentration and evaluate the potential role of hepcidin in SAT diagnosis and monitoring. Methods: Out of 40 patients with SAT initially recruited, restrictive inclusion criteria fulfilled 21 subjects aged 45 ± 10 years and 21 healthy control subjects (CS). HepcidinEL concentration, thyroid status, and iron homeostasis were evaluated at SAT diagnosis and following therapy and compared with CS. Results: The median hepcidinEL concentration at SAT diagnosis is higher than that in CS (48.8 (15.9-74.5) ng/mL vs. 18.2 (10.2-23.3) ng/mL, p = 0.009) and is significantly lower after treatment (4.0 (1.2-10.0) ng/mL, p = 0.007) compared with CS. The ROC analysis for hepcidinEL at SAT diagnosis revealed that area under the curve (AUC) is 0.735 (p = 0.009), and the cut-off for hepcidinEL concentration is 48.8 ng/mL (sensitivity 0.52 and specificity 0.95). HepcidinEL in SAT patients correlated with CRP (r = 0.614, p = 0.003), ferritin (r = 0.815, p < 0.001), and aTPO (r = -0.491, p = 0.024). On multiple regression, the correlation between hepcidinEL and ferritin was confirmed (p < 0.001). Conclusions: SAT is accompanied by a significant increase in hepcidin, which reflects an acute-phase inflammatory process. Parameters of iron homeostasis improved significantly while inflammatory indices got lower following recovery. The potential role of hepcidin as a predictive factor of the risk of SAT relapse needs to be assessed in studies on larger groups of SAT patients.


Assuntos
Hepcidinas/metabolismo , Ferro/metabolismo , Tireoidite Subaguda/metabolismo , Adulto , Feminino , Homeostase/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Vitam Horm ; 110: 101-129, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798807

RESUMO

Iron, an essential nutrient, is required for many biological processes but is also toxic in excess. The lack of a mechanism to excrete excess iron makes it crucial for the body to regulate the amount of iron absorbed from the diet. This regulation is mediated by the hepatic hormone hepcidin. Hepcidin also controls iron release from macrophages that recycle iron and from hepatocytes that store iron. Hepcidin binds to the only known iron export protein, ferroportin, inducing its internalization and degradation and thus limiting the amount of iron released into the plasma. Important regulators of hepcidin, and therefore of systemic iron homeostasis, include plasma iron concentrations, body iron stores, infection and inflammation, hypoxia and erythropoiesis, and, to a lesser extent, testosterone. Dysregulation of hepcidin production contributes to the pathogenesis of many iron disorders: hepcidin deficiency causes iron overload in hereditary hemochromatosis and non-transfused ß-thalassemia, whereas overproduction of hepcidin is associated with iron-restricted anemias seen in patients with chronic inflammatory diseases and inherited iron-refractory iron-deficiency anemia. The present review summarizes our current understanding of the molecular mechanisms and signaling pathways contributing to hepcidin regulation by these factors and highlights the issues that still need clarification.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Hepcidinas/metabolismo , Ferro/farmacologia , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Regulação da Expressão Gênica/fisiologia , Hepcidinas/genética , Humanos , Ferro/metabolismo , Distúrbios do Metabolismo do Ferro/genética , Distúrbios do Metabolismo do Ferro/metabolismo , Transdução de Sinais
7.
Vitam Horm ; 110: 131-141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798808

RESUMO

Hepcidin is a main regulator of iron metabolism, of which abnormal expression affects intestinal absorption and reticuloendothelial sequestration of iron by interacting with ferroportin. It is also noted that abnormal iron accumulation is one of the key factors to facilitate promotion and progression of cancer including hepatoma. In this study, we firstly revealed that a new alternative HAMP transcript was found in hepatoma-derived cell line HLF, which was identical to the wild-type preprohepcidin sequence except lacking of an internal 60 bases. In addition to HLF, most of hepatoma-derived cell lines have significant copy numbers of variant-type hepcidin mRNA by a copy-based-digital PCR. Furthermore, the copy number of hepcidin mRNA variant was significantly higher in serum exosomes of hepatocellular carcinoma patients. The quantification of exosomal hepcidin mRNA variant may serve as a potential new biomarker for HCC diagnosis.


Assuntos
Processamento Alternativo , Exossomos/metabolismo , Hepcidinas/metabolismo , Ferro/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/metabolismo , Estudos de Casos e Controles , Feminino , Variação Genética , Hepcidinas/genética , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
8.
Vitam Horm ; 110: 143-156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798809

RESUMO

Hepcidin expression is determined through transcriptional regulation by systemic iron status. However, acute or chronic inflammation also increases the expression of hepcidin, which is associated with the dysregulation of iron metabolism in pathological conditions. Interleukin (IL)-6 has been suggested to be a principal molecule to confer inflammation-related hepcidin transcription, which is mediated via signal transducer and activator of transcription (STAT)-binding site on the hepcidin promoter. Recently, it has been uncovered that another pro-inflammatory cytokine IL-1ß stimulates hepcidin expression through the distinct mechanism underlying IL-6-mediated hepcidin transcription. In addition to IL-6 induction, IL-1ß stimulates expression of CCAAT-enhancer-binding protein (C/EBP)δ, a transcription factor, leading to transcriptional activation of hepcidin via C/EBP-binding site on the hepcidin promoter. Thus, hepcidin transcription is stimulated through multiple elements in response to proinflammatory cytokines. Relationships between increased production of IL-1ß and dysregulated iron metabolism have been suggested in various diseases, which may be linked to overproduction of hepcidin.


Assuntos
Hepcidinas/metabolismo , Interleucina-1beta/metabolismo , Animais , Regulação da Expressão Gênica , Hepcidinas/genética , Humanos , Inflamação/metabolismo , Interleucina-1beta/genética
9.
Vitam Horm ; 110: 157-188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798810

RESUMO

Hepcidin is considered the major regulator of systemic iron homeostasis in human and mice, and its expression in the liver is mainly regulated at a transcriptional level. Central to its regulation are the bone morphogenetic proteins, particularly BMP6, that are heparin binding proteins. Heparin was found to inhibit hepcidin expression and BMP6 activity in hepatic cell lines and in mice, suggesting that endogenous heparan sulfates are involved in the pathway of hepcidin expression. This was confirmed by the study of cells and mice overexpressing heparanase, the enzyme that hydrolyzes heparan sulfates, and by cellular models with altered heparan sulfates. The evidences supporting the role of heparan sulfate in hepcidin expression are summarized in this chapter and open the way for new understanding in hepcidin expression and its control in pathological condition.


Assuntos
Glucuronidase/metabolismo , Heparina/metabolismo , Heparitina Sulfato/metabolismo , Hepcidinas/metabolismo , Animais , Regulação da Expressão Gênica , Hepcidinas/genética , Humanos
10.
Vitam Horm ; 110: 17-45, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798811

RESUMO

Hepcidin is central to regulation of iron metabolism. Its effect on a cellular level involves binding ferroportin, the main iron export protein, resulting in its internalization and degradation and leading to iron sequestration within ferroportin-expressing cells. Aberrantly increased hepcidin leads to systemic iron deficiency and/or iron restricted erythropoiesis. Furthermore, insufficiently elevated hepcidin occurs in multiple diseases associated with iron overload. Abnormal iron metabolism as a consequence of hepcidin dysregulation is an underlying factor resulting in pathophysiology of multiple diseases and several agents aimed at manipulating this pathway have been designed, with some already in clinical trials. In this chapter, we present an overview of and rationale for exploring the development of hepcidin agonists and antagonists in various clinical scenarios.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Hepcidinas/metabolismo , Distúrbios do Metabolismo do Ferro/genética , Ferro/metabolismo , Animais , Proteínas de Transporte de Cátions/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hepcidinas/genética , Humanos , Ferro/farmacologia , Distúrbios do Metabolismo do Ferro/metabolismo , Distúrbios do Metabolismo do Ferro/terapia , Transdução de Sinais
11.
Vitam Horm ; 110: 189-200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798812

RESUMO

Cellular iron is required for the utilization of oxygen in the cell. Iron in iron-sulfur and heme groups is required for electron transfer and oxygen activation in oxidative phosphorylation, while labile free iron is required for oxygen activation by dioxygenases, and as a catalyst for redox signaling. At the same time, this reactivity with oxygen underpins the production of cell-damaging free radicals in the presence of excess iron. Because the cardiac cell is a major site of oxygen flux, it requires tight control of intracellular iron levels. Until recently, such control was thought to be mediated predominantly by the action of iron regulatory proteins. However, new evidence reveals that cardiomyocyte hepcidin is indispensable for the control of intracellular iron levels, normal metabolism and heart function. This new evidence highlights the need for better understanding of the regulation of cardiomyocyte hepcidin in health and disease.


Assuntos
Hepcidinas/metabolismo , Homeostase , Ferro/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Regulação da Expressão Gênica , Hepcidinas/genética , Humanos
12.
Vitam Horm ; 110: 223-242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798814

RESUMO

Hepcidin, an oligopeptide, has two major functions in mammals. Hepcidin regulates iron homeostasis by controlling iron export from absorptive enterocytes, hepatocytes, and macrophages into the circulation via ferroportin inactivation. Hepcidin is also an innate antimicrobial agent that is induced by invasive bacteria, limits bacterial proliferation by reducing iron in plasma and extracellular fluids, and kills bacteria. Herein, we review hepcidin and hepcidin genes, iron acquisition by bacteria, hepcidin actions in mice infected with selected extracellular and intracellular bacteria, and reports of corresponding serious human infections. We discuss the relevance and uncertainties of mouse infection models to understanding serious infection of humans with iron overload by the same bacterial species.


Assuntos
Infecções Bacterianas/imunologia , Hepcidinas/metabolismo , Ferro/metabolismo , Animais , Bactérias/metabolismo , Hepcidinas/genética , Hepcidinas/farmacologia , Humanos
13.
Vitam Horm ; 110: 243-264, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798815

RESUMO

Chronic kidney disease (CKD) is associated with several complications that worsen with progression of disease; anemia, disturbances in iron metabolism and inflammation are common features. Inflammatory response starts early, releasing pro-inflammatory cytokines, acute phase reactants and hepcidin. Hepcidin production is modulated by several factors, as hypoxia/anemia, erythropoietin and erythropoiesis products, transferrin saturation (TSAT) and liver iron levels, which are altered in CKD. Treatment of CKD anemia is based on pharmaceutical intervention, with erythropoietic stimulating agents and/or iron supplementation; however, in spite of the erythropoietic benefits, this therapy, on a regular basis, involves risks, namely iron overload. To overcome these risks, some therapeutic approaches are under study to target CKD anemia. Considering the actual alerts about risk of iron overload in dialysis patients, inhibition of hepcidin, the central key player in iron homeostasis, could be a pivotal strategy in the management of CKD anemia.


Assuntos
Anemia/etiologia , Hepcidinas/metabolismo , Insuficiência Renal Crônica/complicações , Anemia/metabolismo , Eritropoetina/metabolismo , Regulação da Expressão Gênica , Hepcidinas/genética , Humanos , Ferro/metabolismo , Insuficiência Renal Crônica/patologia
14.
Vitam Horm ; 110: 47-70, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798816

RESUMO

Since its discovery in 2001, there have been a number of important discoveries and findings that have increased our knowledge about the functioning of hepcidin. Hepcidin, the master iron regulator has been shown to be regulated by a number of physiological stimuli and their associated signaling pathways. This chapter will summarize our current understanding of how these physiological stimuli and downstream signaling molecules are involved in hepcidin modulation and ultimately contribute to the regulation of systemic or local iron homeostasis. The signaling pathways and molecules described here have been shown to primarily affect hepcidin at a transcriptional level, but these transcriptional changes correlate with changes in systemic iron levels as well, supporting the functional effects of hepcidin regulation by these signaling pathways.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Hepcidinas/metabolismo , Ferro/metabolismo , Animais , Proteínas de Transporte de Cátions/genética , Regulação da Expressão Gênica , Hepcidinas/genética , Homeostase , Humanos , Transdução de Sinais/fisiologia
15.
Vitam Horm ; 110: 71-99, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798817

RESUMO

Hepcidin, the main regulator of iron metabolism, is synthesized and released by hepatocytes in response to increased body iron concentration and inflammation. Deregulation of hepcidin expression is a common feature of genetic and acquired iron disorders: in Hereditary Hemochromatosis (HH) and iron-loading anemias low hepcidin causes iron overload, while in Iron Refractory Iron Deficiency Anemia (IRIDA) and anemia of inflammation (AI), high hepcidin levels induce iron-restricted erythropoiesis. Hepcidin expression in the liver is mainly controlled by the BMP-SMAD pathway, activated in a paracrine manner by BMP2 and BMP6 produced by liver sinusoidal endothelial cells. The BMP type I receptors ALK2 and ALK3 are responsible for iron-dependent hepcidin upregulation and basal hepcidin expression, respectively. Characterization of animal models with genetic inactivation of the key components of the pathway has suggested the existence of two BMP/SMAD pathway branches: the first ALK3 and HH proteins dependent, responsive to BMP2 for basal hepcidin activation, and the second ALK2 dependent, activated by BMP6 in response to increased tissue iron. The erythroid inhibitor of hepcidin Erythroferrone also impacts on the liver BMP-SMAD pathway although its effect is blunted by pathway hyper-activation. The liver BMP-SMAD pathway is required also in inflammation to cooperate with JAK2/STAT3 signaling for full hepcidin activation. Pharmacologic targeting of BMP-SMAD pathway components or regulators may improve the outcome of both genetic and acquired disorders of iron overload and deficiency by increasing or inhibiting hepcidin expression.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Hepcidinas/metabolismo , Proteínas Smad/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/genética , Regulação da Expressão Gênica/fisiologia , Hepcidinas/genética , Humanos , Ferro/metabolismo , Proteínas Smad/genética
16.
Int Immunopharmacol ; 69: 337-346, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30776642

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder accompanied with hyperalgesia, edema and pain. At least 30% of the patients failed to respond to the available treatments and medications, which yet have a lot of serious adverse effects on patients. So, using novel technologies to produce more efficient medications is needed. According to the role of iron manipulation in inflammatory process, we have synthetized RAc1 nano particle, which contains zinc and has iron chelating property. In the present study, we evaluated RAc1 nano particle effects on hyperalgesia and liver hepcidin and serum IL-1ß and TNF-α expression levels during acute and chronic phases of adjuvant-induced inflammation in male rats and compared its effects with Deferoxamine. METHODS AND MATERIALS: Complete Freund's adjuvant (CFA)-induced arthritis was caused by single subcutaneous injection of CFA into the rat's hind paw on day zero. RAc1 with 100, 200 and 400 ng/kg doses and deferoxamin with doses of 200 mg/kg after diluting in vehicles were administered daily (i.p.) during the 21 days of the study after CFA injection. Hyperalgesia, Edema, liver hepcidin and serum IL-1ß and TNF-α expression levels were assessed on days 0, 7, 14 and 21 of the study. RESULTS: The results of this study indicated the role of RAc1 nano particle administration in reducing paw edema, thermal hyperalgesia, and liver hepcidin and serum IL-1ß and TNF-α expression even in comparison with Deferoxamine during different phases of inflammation caused by CFA. CONCLUSION: It seems that RAc1 nano particle exerts its immune modulatory effects by decreasing liver hepcidin expression and serum IL-1ß and TNF-α levels.


Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Nanopartículas/uso terapêutico , Animais , Desferroxamina/uso terapêutico , Hepcidinas/metabolismo , Humanos , Interleucina-1beta/sangue , Irã (Geográfico) , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Sideróforos/uso terapêutico , Fator de Necrose Tumoral alfa/sangue
17.
Turk J Med Sci ; 49(1): 74-80, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30761871

RESUMO

Background/aim: GDF15, hepcidin and mitoferrin-1 (mfrn-1) are proteins involved in systemic iron regulation. There are no studies in the literature demonstrating the serum mfrn-1 levels in polycythemia vera (PV) and essential thrombocythemia (ET) patients. The aim of this study was to investigate GDF15, hepcidin and mfrn-1 levels in PV and ET patients. Materials and methods: Ten PV, 17 ET patients, and 27 healthy controls (HCs) were enrolled. GDF15, hepcidin and mfrn-1 values were measured with enzyme-linked immunosorbent assay (ELISA). Results: GDF15 levels were higher in the myeloproliferative neoplasm (MPN) group (P = 0.002). Hepcidin levels were not different between MPN patients and HCs. The mfrn-1 levels were lower in MPN patients (P = 0.039). Hepcidin, GDF15, and mfrn-1 levels were not different between PV and ET patients. mfrn-1 levels were lower in ET patients than HCs (P = 0.038). Conclusion: Increased erythropoiesis in MPNs may lead to high GDF15 levels in these patients. However, hepcidin was not suppressed despite the increased GDF15 levels and erythropoiesis in these patients. Decrease in mfrn-1 in MPNs can be the result of its increased turnover due to increased myelopoiesis. It can be hypothesized that similar hepcidin levels in patients and controls and low mfrn-1 levels in patients may be a defense mechanism against erythroid activity and thromboembolic complications.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Fator 15 de Diferenciação de Crescimento/metabolismo , Hepcidinas/metabolismo , Ferro/metabolismo , Proteínas Mitocondriais/metabolismo , Policitemia Vera/metabolismo , Trombocitemia Essencial/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Proteínas de Transporte de Cátions/sangue , Feminino , Fator 15 de Diferenciação de Crescimento/sangue , Hepcidinas/sangue , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/sangue , Policitemia Vera/sangue , Trombocitemia Essencial/sangue
18.
Food Funct ; 10(2): 723-732, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30664135

RESUMO

Microalgae are potential iron supplements for improving iron deficiency through an unknown mechanism. To analyze the increase in non-heme iron absorption caused by microalgae, six different microalgal feeds were prepared from Spirulina, Chlorella and Synechococcus sp. PCC 7002 as the main source of dietary iron (25 mg kg-1; denoted as H-Sp, H-Ch, and H-Sy, respectively) or as a partial source of dietary iron (5 mg kg-1; denoted as L-Sp, L-Ch, and L-Sy, respectively) to suppress iron-deficiency anemia in rats. The hemoglobin regeneration efficiencies in anemic rats were in the order ferric citrate (34.7 ± 1.8%) < H-Ch (49.9 ± 4.1%) ≈ H-Sy (50.6 ± 5.3%) ≈ L-Sp (46.9 ± 6.2%) ≈ L-Ch (43.1 ± 6.9%) ≈ L-Sy (43.5 ± 2.4%) ≈ FeSO4 (47.2 ± 4.9%) < H-Sp (54.8 ± 5.5%). The percentage content of intestinal nanosized iron in the H-Sp, H-Ch, and H-Sy treatment groups was significantly higher than that in the L-Sp, L-Ch, and L-Sy groups, and was significantly higher in the microalgal diet groups than in the ferric citrate group, providing strong evidence for nanosized iron supplementation from microalgae. Overall, microalgae, especially Spirulina, are functional iron nutritive fortifiers that can supply intestinal nanosized iron.


Assuntos
Anemia Ferropriva/dietoterapia , Ferro na Dieta/administração & dosagem , Ferro na Dieta/uso terapêutico , Microalgas , Ração Animal/análise , Animais , Chlorella , Dieta/veterinária , Suplementos Nutricionais , Hemoglobinas/metabolismo , Hepcidinas/metabolismo , Ferro/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Spirulina , Baço/metabolismo
19.
Dev Comp Immunol ; 94: 11-15, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30659854

RESUMO

Hepcidin is an antimicrobial peptide and an iron regulatory protein that prevents the release of excess iron in the blood. There is evidence suggesting that teleost hepcidin is a major player in antimicrobial defense against various bacteria species, but little is known regarding the effects of teleost hepcidin in protozoan parasitic infections. We examined the role of hepcidin during the course of infection of goldfish with Trypanosoma carassii. Quantitative real-time PCR was used to determine the expression of hepcidin in goldfish immune organs during the course of T. carassii infection. During the acute phase of the T. carassii infection, the mRNA levels of hepcidin were up-regulated in liver and kidney. In contrast, an up-regulation of hepcidin mRNA expression in spleen was observed during the chronic phase of the infection. Furthermore, a synthetic goldfish hepcidin peptide induced trypanosome lysis in vitro, and parasite surface disruption was confirmed by scanning electron microscopy (SEM) analysis. These results suggest that, in addition to well-characterized direct antibacterial activities, teleost hepcidin also exhibits trypanocidal activity.


Assuntos
Anti-Infecciosos/metabolismo , Doenças dos Peixes/imunologia , Carpa Dourada/imunologia , Hepcidinas/metabolismo , Macrófagos/imunologia , Trypanosoma/imunologia , Tripanossomíase/imunologia , Animais , Citocinas/metabolismo , Imunidade Inata , Transcriptoma , Regulação para Cima
20.
Transfusion ; 59(1): 226-231, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30536387

RESUMO

BACKGROUND: Blood donors have an increased risk of low hemoglobin (Hb) levels due to iron deficiency. Therefore, knowledge of genetic variants associated with low Hb could facilitate individualized donation intervals. We have previously reported three specific single-nucleotide polymorphisms that were associated with ferritin levels in blood donors. In this study, we investigated the effect of these single-nucleotide polymorphisms on Hb levels in 15,567 Danish blood donors. STUDY DESIGN AND METHODS: We studied 15,567 participants in the Danish Blood Donor Study. The examined genes and single-nucleotide polymorphisms were 1) TMPRSS6, involved in regulation of hepcidin: rs855791; 2) HFE, associated with hemochromatosis: rs1800562 and rs1799945; 3) BTBD9, associated with restless leg syndrome: rs9357271; and 4) TF, encoding transferrin: rs2280673 and rs1830084. Associations with Hb levels and risk of Hb deferral were assessed in multivariable linear and logistic regression models. RESULTS: The HFE,rs1800562 G-allele and the HFE rs1799945 C-allele were associated with lower Hb levels in men and women, and with an increased risk of Hb below 7.8 mmol/L (12.5 g/dL) in women. Only the rs1799945 C-allele increased the risk of Hb below 8.4 mmol/L (13.5 g/dL) in men. In TMPRSS6, the rs855791 T-allele was associated with lower Hb levels in both men and women, and with an increased risk of low Hb among women. CONCLUSION: With this study we demonstrate that HFE and TMPRSS6 are associated with Hb levels and risk of Hb below the limit of deferral. Thus, genetic testing may be useful in a future assay for personalized donation intervals.


Assuntos
Doadores de Sangue , Hemoglobinas/metabolismo , Alelos , Dinamarca , Feminino , Proteína da Hemocromatose/genética , Hepcidinas/metabolismo , Humanos , Masculino , Proteínas de Membrana/genética , Serina Endopeptidases/genética
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