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2.
Klin Lab Diagn ; 64(8): 477-480, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31479602

RESUMO

This research paper presents the results of a study of some indicators of iron metabolism in anaemia in pregnant women. The venous blood of 39 pregnant women with anaemia was examined. Serum ferritin, ferroportin and hepcidin were investigated for this purpose. The comparison group consisted of 19 pregnant women without anaemia. The haemoglobin concentration was measured by using «Mythic-18¼ haematological autoanalyzer. The concentrations of hepcidin and ferroportin were determined by using «Cloud-Clone Corp.¼ (USA), and ferritin concentrations were determined by using «Pishtaz teb¼ (Iran) reagents through enzyme-linked immunosorbent assay (ELISA) method. The study revealed a significant decrease in the level of ferritin, hepcidin and a significant increase in ferroportin level. A comprehensive definition of various indicators of iron metabolism provides important information not only for understanding the pathogenesis of iron deficiency anaemia in pregnant women but also for early diagnosis of the disease and the appointment of the correct treatment.


Assuntos
Anemia Ferropriva/sangue , Citocinas/sangue , Ferro/metabolismo , Complicações Hematológicas na Gravidez/sangue , Feminino , Ferritinas/sangue , Hepcidinas/sangue , Humanos , Gravidez
3.
Adv Exp Med Biol ; 1173: 1-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456202

RESUMO

Iron is the most abundant trace element in the human body. It is well known that iron is an important component of hemoglobin involved in the transport of oxygen. As a component of various enzymes, it participates in the tricarboxylic acid cycle and oxidative phosphorylation. Iron in the nervous system is also involved in the metabolism of catecholamine neurotransmitters and is involved in the formation of myelin. Therefore, iron metabolism needs to be strictly regulated. Previous studies have shown that iron deficiency in the brain during infants and young children causes mental retardation, such as delayed development of language and body balance, and psychomotor disorders. However, if the iron is excessively deposited in the aged brain, it is closely related to the occurrence of various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Friedreich's ataxia. Therefore, it is important to fully study and understand the mechanism of brain iron metabolism and its regulation. On this basis, exploring the relationship between brain iron regulation and the occurrence of nervous system diseases and discovering new therapeutic targets related to iron metabolism have important significance for breaking through the limitation of prevention and treatment of nervous system diseases. This review discusses the complete research history of iron and its significant role in the pathogenesis of the central nervous system (CNS) diseases.


Assuntos
Encéfalo/metabolismo , Doenças do Sistema Nervoso Central , Ferro/metabolismo , Humanos , Distúrbios do Metabolismo do Ferro , Doenças Neurodegenerativas
4.
Adv Exp Med Biol ; 1173: 21-32, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456203

RESUMO

Iron is an essential trace element in the human body, but excess iron is toxic as it contributes to oxidative damage. To keep iron concentration within the optimal physiologic range, iron metabolism at the cellular level and the whole systemic level are tightly regulated. Balance of iron homeostasis depends on the expression levels and activities of iron carriers, iron transporters, and iron regulatory and storage proteins. Divalent metal transporter 1 (DMT1) at the apical membrane of intestinal enterocyte brings in non-heme iron from the diet, whereas ferroportin 1 (FPN1) at the basal membrane exports iron into the circulation. Plasma transferrin (Tf) then carries iron to various tissues and cells. After binding to transferrin receptor 1 (TfR1), the complex is endocytosed into the cell, where iron enters the cytoplasm via DMT1 on the endosomal membrane. Free iron is either utilized in metabolic processes, such as synthesis of hemoglobin and Fe-S cluster, or sequestered in the cytosolic ferritin, serving as a cellular iron store. Excess iron can be exported from the cell via FPN1. The liver-derived peptide hepcidin plays a major regulatory role in controlling FPN1 level in the enterocyte, and thus controls the whole-body iron absorption. Inside the cells, iron regulatory proteins (IRPs) modulate the expressions of DMT1, TfR1, ferritin, and FPN1 via binding to the iron-responsive element (IRE) in their mRNAs. Both the release of hepcidin and the IRP-IRE interaction are coordinated with the fluctuation of the cellular iron level. Therefore, an adequate and steady iron supplement is warranted for the utilization of cells around the body. Investigations on the molecular mechanisms of cellular iron metabolism and regulation could advance the fields of iron physiology and pathophysiology.


Assuntos
Ferro/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Enterócitos/metabolismo , Ferritinas/metabolismo , Homeostase , Humanos , Sobrecarga de Ferro , Receptores da Transferrina/metabolismo , Fatores de Transcrição/metabolismo , Transferrina/metabolismo
5.
Adv Exp Med Biol ; 1173: 33-44, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456204

RESUMO

With the development of research, more and more evidences suggested that mutations in the genes associated with brain iron metabolism induced diseases in the brain. Brain iron metabolism disorders might be one cause of neurodegenerative diseases. This review mainly summarizes the normal process of iron entry into the brain across the blood-brain barrier, and the distribution and transportation of iron among neurons and glial cells, as well as the underlying regulation mechanisms. To understand the mechanisms of iron metabolism in the brain will provide theoretical basis to prevent and cure brain diseases related to iron metabolism disorders.


Assuntos
Encéfalo/metabolismo , Distúrbios do Metabolismo do Ferro , Ferro/metabolismo , Barreira Hematoencefálica , Humanos , Neuroglia/metabolismo , Neurônios/metabolismo
6.
Adv Exp Med Biol ; 1173: 45-66, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456205

RESUMO

The key molecular events that provoke Parkinson's disease (PD) are not fully understood. Iron deposit was found in the substantia nigra pars compacta (SNpc) of PD patients and animal models, where dopaminergic neurons degeneration occurred selectively. The mechanisms involved in disturbed iron metabolism remain unknown, however, considerable evidence indicates that iron transporters dysregulation, activation of L-type voltage-gated calcium channel (LTCC) and ATP-sensitive potassium (KATP) channels, as well as N-methyl-D-aspartate (NMDA) receptors (NMDARs) contribute to this process. There is emerging evidence on the structural links and functional modulations between iron and α-synuclein, and the key player in PD which aggregates in Lewy bodies. Iron is believed to modulate α-synuclein synthesis, post-translational modification, and aggregation. Furthermore, glia, especially activated astroglia and microglia, are involved in iron deposit in PD. Glial contributions were largely dependent on the factors they released, e.g., neurotrophic factors, pro-inflammatory factors, lactoferrin, and those undetermined. Therefore, iron chelation using iron chelators, the extracts from many natural foods with iron chelating properties, may be an effective therapy for prevention and treatment of the disease.


Assuntos
Ferro/metabolismo , Doença de Parkinson/fisiopatologia , alfa-Sinucleína/metabolismo , Animais , Canais de Cálcio Tipo L , Neurônios Dopaminérgicos/patologia , Humanos , Canais KATP , Receptores de N-Metil-D-Aspartato , Substância Negra/patologia
7.
Adv Exp Med Biol ; 1173: 67-104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456206

RESUMO

Alzheimer's disease (AD) is a multifactorial neurodegenerative condition associated with pathological accumulation of amyloid plaques and with the appearance of deposit of neurofibrillary tangles. Increasing evidence suggests that disorders of metal ion metabolism in the brain are one of the risk factors for the pathogenesis of AD. Iron, one of the endogenous metal ions, involves in many important physiological activities in the brain. Iron metabolism mainly depends on iron regulatory proteins including ferritin, transferrin and transferrin receptor, hepcidin, ferroportin, lactoferrin. Abnormal iron metabolism generates hydroxyl radicals through the Fenton reaction, triggers oxidative stress reactions, damages cell lipids, protein and DNA structure and function, leads to cell death, and ultimately influences the process of ß-amyloid (Aß) misfolding and plaque aggregation. Although the results are different, in general, iron has deposition in different brain regions of AD patients, which may impair normal cognitive function and behavior. Therefore, neuroimaging changes have so far been largely attributed to focal iron deposition accompanying the plaques at preclinical stages of AD, and iron-targeted therapeutic strategies have become a new direction. Iron chelators have received a great deal of attention and have obtained good results in scientific experiments and some clinical trials. Future research will also focus on iron as an opportunity to study the mechanism of the occurrence and development of AD from the iron steady state to more fully clarify the etiology and prevention strategies.


Assuntos
Doença de Alzheimer/patologia , Encéfalo/metabolismo , Ferro/metabolismo , Peptídeos beta-Amiloides , Encéfalo/fisiopatologia , Humanos , Emaranhados Neurofibrilares/patologia , Placa Amiloide/patologia
8.
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
9.
Adv Exp Med Biol ; 1173: 125-143, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456208

RESUMO

Friedreich's ataxia (FRDA) is a degenerative disease that affects both the central and the peripheral nervous systems and non-neural tissues including, mainly, heart, and endocrine pancreas. It is an autosomal recessive disease caused by a GAA triplet-repeat localized within an Alu sequence element in intron 1 of frataxin (FXN) gene, which encodes a mitochondrial protein FXN. This protein is essential for mitochondrial function by the involvement of iron-sulfur cluster biogenesis. The effects of its deficiency also include disruption of cellular, particularly mitochondrial, iron homeostasis, i.e., relatively more iron accumulated in mitochondria and less iron presented in cytosol. Though iron toxicity is commonly thought to be mediated via Fenton reaction, oxidative stress seems not to be the main problem to result in detrimental effects on cell survival, particularly neuron survival. Therefore, the basic research on FXN function is urgently demanded to understand the disease. This chapter focuses on the outcome of FXN expression, regulation, and function in cellular or animal models of FRDA and on iron pathophysiology in the affected tissues. Finally, therapeutic strategies based on the control of iron toxicity and iron cellular redistribution are considered. The combination of multiple therapeutic targets including iron, oxidative stress, mitochondrial function, and FXN regulation is also proposed.


Assuntos
Ataxia de Friedreich/fisiopatologia , Ferro/metabolismo , Animais , Humanos , Proteínas de Ligação ao Ferro/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais , Estresse Oxidativo
10.
Adv Exp Med Biol ; 1173: 145-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456209

RESUMO

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of motor neurons in the motor cortex, brainstem, and spinal cord. The etiology and pathogenesis of this devastating disease remain largely unknown. Increasing evidence suggests that iron accumulation is involved in the onset and progression of ALS. In this review, we discuss the regulation of iron homoeostasis in the brain, the misregulation of iron homeostasis in ALS, and its possible roles in the mechanism of the disease. Finally, we summarize the recent progress and problems with respect to iron chelator therapies on ALS, aiming to propose a new therapeutic strategy to ameliorate the progression of the disease.


Assuntos
Esclerose Amiotrófica Lateral/fisiopatologia , Encéfalo/metabolismo , Ferro/metabolismo , Homeostase , Humanos , Neurônios Motores/patologia , Degeneração Neural
11.
Adv Exp Med Biol ; 1173: 153-177, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456210

RESUMO

Neurodegeneration with brain iron accumulation (NBIA) is a group of seriously devastating and life-threatening rare monogenic diseases characterized by focal iron accumulation in the brain. The main symptoms of NBIA comprise progressive movement disorder, often including painful dystonia, parkinsonism, mental disability, and early death. Currently, a single established therapy is not available to reverse the progression of these debilitating disorders. The complexity of NBIA emerged from the identification of various causative genes, and up to 15 genes have been identified to date. Although the NBIA genes are involved in different cellular biochemical pathways, they show the common characteristic of generating severe iron accumulation in the basal ganglia of the patients' brains. Thus, the molecular events that lead to brain iron overload and their important roles in the pathophysiology of the diseases are not easy to identify and are poorly understood. This review summarizes the current knowledge on NBIA disorders, with a particular focus on the data describing the role of iron in the pathogenic mechanisms.


Assuntos
Encéfalo/fisiopatologia , Ferro/metabolismo , Gânglios da Base , Encéfalo/metabolismo , Humanos , Sobrecarga de Ferro , Doenças Neurodegenerativas
12.
Bioresour Technol ; 291: 121858, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31377515

RESUMO

The improved performances during anaerobic degradation of phenol to methane with Fe(OH)3 were usually inapparent, due to its lower solubility (unaccessible to dissimilatory iron reduction) and more positive reduction potential of Fe(III)/Fe(II) (unfavorable for enriching Fe(III)-reducing bacteria [IRBs]). In this study, citrate, the organic chelates, were used to solubilize Fe(III) with the aim of improving the phenol degradation and declining the reduction potential of Fe(III)/Fe(II). Results showed that, in the co-occurrence of citrate and Fe(OH)3, the degradation rates of phenol were about 1.3-fold rapider than that with sole Fe(OH)3. Analysis of cyclic voltammetry demonstrated that the reduction potential of Fe(III)/Fe(II) in the form of Fe(OH)3 (-0.41 to -0.28 V vs Ag/AgCl) declined to -0.61 to -0.41 V. As a result, the Fe(III)-reducing genera, such as Petrimonas and Shewanella, which held a great potential of proceeding syntrophic metabolism via direct interspecies electron transfer (DIET), were significantly enriched.


Assuntos
Quelantes/farmacologia , Compostos Férricos/metabolismo , Ferro/metabolismo , Metano/metabolismo , Fenol/metabolismo , Anaerobiose , Bacteroides/efeitos dos fármacos , Bacteroides/metabolismo , Transporte de Elétrons , Oxirredução , Fenóis/metabolismo , Shewanella/efeitos dos fármacos , Shewanella/metabolismo
13.
Bioresour Technol ; 291: 121874, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31377508

RESUMO

Anaerobic digestion is widely employed for treating phenol-containing wastewater, but there are still some drawbacks such as slow phenol degradation rate and vulnerable acetoclastic methanogens. Coupling of magnetite (Fe3O4) and zero valent iron (ZVI) was firstly used to enhance anaerobic digestion of phenol. The results indicated an obvious synergistic effect was generated with coupling of Fe3O4 and ZVI during the whole anaerobic digestion of phenol. The phenol degradation rate and methane production of Fe3O4/ZVI-added group were increased by 8.8-23.1% and 11.9-31.6%, respectively compared with Fe3O4-added group, and enhanced by 5.9-17.1% and 4.4-18.3%, respectively compared with ZVI-added group. ZVI improved the growth of hydrogenotrophic methanogens and Fe3O4 enhanced the growth of syntrophic acetate-oxidizing bacteria. Finally, the syntrophic interaction between acetate-oxidizing bacterium and hydrogenotrophic methanogens played a vital role on the synergistic effect of Fe3O4 and ZVI on the whole anaerobic phenol digestion.


Assuntos
Fenol/metabolismo , Ácido Acético/metabolismo , Anaerobiose , Euryarchaeota/metabolismo , Óxido Ferroso-Férrico , Ferro/metabolismo , Metano/metabolismo
14.
Arch Insect Biochem Physiol ; 102(1): e21592, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31276235

RESUMO

Ferritin, which is ubiquitous among all living organisms, plays a crucial role in maintaining iron homeostasis, immune response, and detoxification. In the present research, we identified an iron-binding protein, ferritin heavy chain subunit, from Papilio xuthus and named PxFerHCH. The complete complementary DNA of PxFerHCH was 1,252 bp encoding a sequence of 211 amino acids, which includes an iron-responsive element. Phylogenetic analysis showed that PxFerHCH is clustered with Manduca sexta and Galleria mellonella ferritin heavy chain subunits. Expression levels of PxFerHCH in various tissues were analyzed by reverse transcription quantitative polymerase chain reaction, and the results exhibited that PxFerHCH was expressed in all tissues with the highest expression in the fat body. The relative expression level of PxFerHCH in response to bacterial (Escherichia coli and Staphylococcus aureus) challenges sharply increased by about 12 hr postinfection (hpi) and then decreased at 24 hpi. In addition, the iron-binding capacity and antioxidation activity of recombinant PxFerHCH protein were also investigated. These results reveal that PxFerHCH might play an important role in defense against bacterial infection.


Assuntos
Apoferritinas/metabolismo , Borboletas/metabolismo , Ferro/metabolismo , Sequência de Aminoácidos , Animais , Apoferritinas/genética , Apoferritinas/isolamento & purificação , Sequência de Bases , Borboletas/genética , Borboletas/imunologia , Escherichia coli , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Staphylococcus aureus
15.
Plant Mol Biol ; 101(1-2): 129-148, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31267256

RESUMO

Iron and phosphorus are abundant elements in soils but poorly available for plant nutrition. The availability of these two nutrients represents a major constraint for fruit tree cultivation such as apple (Malus × domestica) leading very often to a decrease of fruit productivity and quality worsening. Aim of this study was to characterize common and specific features of plant response to Fe and P deficiencies by ionomic, transcriptomic and exudation profiling of apple roots. Under P deficiency, the root release of oxalate and flavonoids increased. Genes encoding for transcription factors and transporters involved in the synthesis and release of root exudates were upregulated by P-deficient roots, as well as those directly related to P acquisition. In Fe-deficiency, plants showed an over-accumulation of P, Zn, Cu and Mn and induced the transcription of those genes involved in the mechanisms for the release of Fe-chelating compounds and Fe mobilization inside the plants. The intriguing modulation in roots of some transcription factors, might indicate that, in this condition, Fe homeostasis is regulated by a FIT-independent pathway. In the present work common and specific features of apple response to Fe and P deficiency has been reported. In particular, data indicate similar modulation of a. 230 genes, suggesting the occurrence of a crosstalk between the two nutritional responses involving the transcriptional regulation, shikimate pathway, and the root release of exudates.


Assuntos
Ferro/deficiência , Malus/fisiologia , Fósforo/deficiência , Transcriptoma , Transporte Biológico , Perfilação da Expressão Gênica , Homeostase , Ferro/metabolismo , Malus/genética , Fósforo/metabolismo , Exsudatos de Plantas/metabolismo , Folhas de Planta/genética , Folhas de Planta/fisiologia , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Análise de Sequência de RNA
16.
J Agric Food Chem ; 67(29): 8096-8106, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31260296

RESUMO

Field experiments were conducted on wheat to study the effects of foliar-applied iodine(I) alone, Zn (zinc) alone, and a micronutrient cocktail solution containing I, Zn, Se (selenium), and Fe (iron) on grain yield and grain concentrations of micronutrients. Plants were grown over 2 years in China, India, Mexico, Pakistan, South Africa, and Turkey. Grain-Zn was increased from 28.6 mg kg-1 to 46.0 mg-1 kg with Zn-spray and 47.1 mg-1 kg with micronutrient cocktail spray. Foliar-applied I and micronutrient cocktail increased grain I from 24 µg kg-1 to 361 µg kg-1 and 249 µg kg-1, respectively. Micronutrient cocktail also increased grain-Se from 90 µg kg-1 to 338 µg kg-1 in all countries. Average increase in grain-Fe by micronutrient cocktail solution was about 12%. The results obtained demonstrated that foliar application of a cocktail micronutrient solution represents an effective strategy to biofortify wheat simultaneously with Zn, I, Se and partly with Fe without yield trade-off in wheat.


Assuntos
Biofortificação/métodos , Produção Agrícola/métodos , Iodo/metabolismo , Ferro/metabolismo , Selênio/metabolismo , Triticum/metabolismo , Zinco/metabolismo , China , Fertilizantes/análise , Índia , Iodo/análise , Ferro/análise , México , Micronutrientes/análise , Micronutrientes/metabolismo , Paquistão , Folhas de Planta/química , Folhas de Planta/metabolismo , Sementes/química , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Selênio/análise , África do Sul , Triticum/química , Triticum/crescimento & desenvolvimento , Turquia , Zinco/análise
17.
World J Microbiol Biotechnol ; 35(8): 117, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332532

RESUMO

Iron- and sulfur-oxidizing bacteria inhabiting rice rhizoplane play a significant role on arsenic biogeochemistry in flooded rice paddies, influencing arsenic translocation to rice grains. In the present study, the selective pressure of arsenic species on these microbial populations was evaluated. Rice roots from continuously flooded plants were incubated in iron sulfide (FeS) gradient tubes and exposed to either arsenate or arsenite. The biomass developed in the visible iron-oxidation band of the enrichments was analyzed by Scanning Electron Microscopy and Energy-Dispersive Spectroscopy (SEM-EDS) and the bacterial communities were characterized by 16S rRNA gene sequencing. Different Proteobacteria communities were selected depending on exposure to arsenate and arsenite. Arsenate addition favored the versatile iron-oxidizers Dechloromonas and Azospira, associated to putative iron (hydr)oxide crystals. Arsenite exposure decreased the diversity in the enrichments, with the development of the sulfur-oxidizer Thiobacillus thioparus, likely growing on sulfide released by FeS. Whereas sulfur-oxidizers were observed in all treatments, iron-oxidizers disappeared when exposed to arsenite. These results reveal a strong impact of different inorganic arsenics on rhizospheric iron-oxidizers as well as a crucial role of sulfur-oxidizing bacteria in establishing rice rhizosphere communities under arsenic pressure.


Assuntos
Arsênico/metabolismo , DNA Bacteriano/isolamento & purificação , Oryza/efeitos dos fármacos , Oryza/microbiologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/microbiologia , Arseniatos/metabolismo , Arsenitos/metabolismo , DNA Bacteriano/genética , Ferro/metabolismo , Oxirredução , Proteobactérias/efeitos dos fármacos , Proteobactérias/isolamento & purificação , Proteobactérias/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/isolamento & purificação , Solo/química , Microbiologia do Solo , Poluentes do Solo/metabolismo , Enxofre/metabolismo
18.
Nat Commun ; 10(1): 2935, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31270335

RESUMO

Trace elements play important roles in human health, but little is known about their functions in humoral immunity. Here, we show an important role for iron in inducing cyclin E and B cell proliferation. We find that iron-deficient individuals exhibit a significantly reduced antibody response to the measles vaccine when compared to iron-normal controls. Mice with iron deficiency also exhibit attenuated T-dependent or T-independent antigen-specific antibody responses. We show that iron is essential for B cell proliferation; both iron deficiency and α-ketoglutarate inhibition could suppress cyclin E1 induction and S phase entry of B cells upon activation. Finally, we demonstrate that three demethylases, KDM2B, KDM3B and KDM4C, are responsible for histone 3 lysine 9 (H3K9) demethylation at the cyclin E1 promoter, cyclin E1 induction and B cell proliferation. Thus, our data reveal a crucial role of H3K9 demethylation in B cell proliferation, and the importance of iron in humoral immunity.


Assuntos
Linfócitos B/imunologia , Proliferação de Células , Histonas/química , Histonas/imunologia , Imunidade Humoral , Lisina/imunologia , Animais , Linfócitos B/química , Linfócitos B/citologia , Ciclo Celular , Células Cultivadas , Ciclina E/genética , Ciclina E/imunologia , Desmetilação , Proteínas F-Box/genética , Proteínas F-Box/imunologia , Histonas/genética , Ferro/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/imunologia , Ativação Linfocitária , Lisina/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/imunologia , Regiões Promotoras Genéticas , Linfócitos T/citologia , Linfócitos T/imunologia
20.
Pestic Biochem Physiol ; 157: 161-168, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153464

RESUMO

Paraquat (PQ) is a widely used herbicide with no antidote which is implicated in the pathogenesis of the Parkinson's disease. The present study then investigated the potential of caffeic acid (CA), a known antioxidant, cardioprotective and neuroprotective molecule to counteract oxidative stress mediated by PQ. In addition, molecular docking was performed to understand the mechanism underlying the inhibitory effect of CA against PQ poisoning. The fruit fly, Drosophila melanogaster, was exposed to PQ (0.44 mg/g of diet) in the absence or presence of CA (0.25, 0.5, 1 and 2 mg/g of died) for 7 days. Data showed that PQ-fed flies had higher incidence of mortality which was associated with mitochondrial dysfunction, increased free Fe(II) content and lipid peroxidation when compared to the control. Co-exposure with CA reduced mortality and markedly attenuated biochemical changes induced by PQ. The mechanism investigated using molecular docking revealed a strong interaction (-6.2 Kcal/mol) of CA with D. melanogaster transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2). This was characterized by the binding of CA to keap-1 domain of Nrf2. Taking together these results indicate the protective effect of CA against PQ-induced oxidative damage in D. melanogaster was likely through its coordination which hinders Nrf2-keap-1 binding leading to an increase of the antioxidant defense system.


Assuntos
Ácidos Cafeicos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Paraquat/farmacologia , Animais , Drosophila melanogaster , Ferro/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética
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