Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.286
Filtrar
1.
Food Chem ; 386: 132827, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35364499

RESUMO

The structure and function of ferritin from seafood has been largely unexplored. In this study, homopolymeric scallop ferritin (ApF) was prepared for the first time, the apo form of which exhibited the stronger ability to protect DNA from iron-induced oxidative damage as compared to its analogue, homopolymeric shrimp ferritin (MjF). Their difference in DNA-protective activity was derived from less hydroxyl radicals produced during iron oxidation in the presence of scallop ferritin than shrimp ferritin. The kinetic results showed that apo-ApF catalyzed the faster ferrous ions oxidation by oxygen into nontoxic ferric ions as compared to apo-MjF. Newly reported crystal structure of ApF revealed that its stronger ferroxidase activity stemmed from different structures in the triple axis channel and ferroxidase site as compared to MjF. All these new findings advance our understanding of the relationship between the structure and function of food-related protein.


Assuntos
Ferritinas , Pectinidae , Animais , Ceruloplasmina , DNA/metabolismo , Ferritinas/metabolismo , Radical Hidroxila/metabolismo , Ferro/química , Oxirredução , Estresse Oxidativo , Pectinidae/genética , Pectinidae/metabolismo , Alimentos Marinhos
2.
Sheng Wu Gong Cheng Xue Bao ; 38(4): 1602-1611, 2022 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-35470630

RESUMO

Enzyme separation, purification, immobilization, and catalytic performance improvement have been the research hotspots and frontiers as well as the challenges in the field of biocatalysis. Thus, the development of novel methods for enzyme purification, immobilization, and improvement of their catalytic performance and storage are of great significance. Herein, ferritin was fused with the lichenase gene to achieve the purpose. The results showed that the fused gene was highly expressed in the cells of host strains, and that the resulted fusion proteins could self-aggregate into carrier-free active immobilized enzymes in vivo. Through low-speed centrifugation, the purity of the enzymes was up to > 90%, and the activity recovery was 61.1%. The activity of the enzymes after storage for 608 h was higher than the initial activity. After being used for 10 cycles, it still maintained 50.0% of the original activity. The insoluble active lichenase aggregates could spontaneously dissolve back into the buffer and formed the soluble polymeric lichenases with the diameter of about 12 nm. The specific activity of them was 12.09 times that of the free lichenase, while the catalytic efficiency was 7.11 times and the half-life at 50 ℃ was improved 11.09 folds. The results prove that the ferritin can be a versatile tag to trigger target enzyme self-aggregation and oligomerization in vivo, which can simplify the preparation of the target enzymes, improve their catalysis performance, and facilitate their storage.


Assuntos
Ferritinas , Glicosídeo Hidrolases , Biocatálise , Enzimas Imobilizadas/metabolismo , Ferritinas/genética , Ferritinas/metabolismo , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo
3.
Oxid Med Cell Longev ; 2022: 9598211, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464768

RESUMO

Oxidative stress (OS) is considered a significant risk factor for the development of anemia in patients treated by regular hemodialysis (HD). Moreover, OS represents a risk factor for the development of erythropoietin (EPO) resistance in these patients. The aim of this study was to examine the role of OS regarding EPO resistance development in patients treated by regular HD. 96 patients treated with standard HD and on-line hemodiafiltration were included in this study. The patients were treated with short-acting and long-acting EPOs for anemia. The concentration of superoxide anion radical, hydrogen peroxide, thiobarbituric acid reactive substances, and nitric oxide in the form of nitrites and the activity of catalase, superoxide dismutase and reduced glutathione were measured in patients' blood spectrophotometrically. Standard biochemical analysis, inflammatory markers, nutritional status, HD parameters, and erythropoietin resistance index were also determined. Patients with resistance to short-acting EPO had significantly lower concentration of hemoglobin in the blood and hematocrit value, a significantly higher serum ferritin concentration, and significantly lower catalase activity in erythrocytes than patients without EPO resistance. Patients with resistance to long-acting EPO have a significantly lower hemoglobin concentration in the blood, hematocrit values, and serum concentration of prealbumin and vitamin D, as well as significantly higher concentration of C-reactive protein, superoxide anion, and hydrogen peroxide concentration than those without resistance. OS significantly contributes to EPO resistance development. OS, higher ferritin and CRP levels, lower hemoglobin, hematocrit and prealbumin levels, and vitamin D deficiency represent significant risk factors for EPO resistance development in HD patients.


Assuntos
Anemia , Eritropoetina , Falência Renal Crônica , Anemia/etiologia , Proteína C-Reativa/metabolismo , Catalase/metabolismo , Feminino , Ferritinas/metabolismo , Hemoglobinas/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Estresse Oxidativo , Pré-Albumina/metabolismo , Proteínas Recombinantes/metabolismo , Diálise Renal/efeitos adversos , Superóxidos/metabolismo
4.
Arh Hig Rada Toksikol ; 73(1): 48-61, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35390238

RESUMO

Ferritin is the main intracellular storage of iron. Animal studies show that female liver and kidney express more ferritin and accumulate more iron than male. However, no study so far has investigated sex and age differences in light (FtL) and heavy (FtH) ferritin chain expression. To address this, we relied on specific antibodies and immunochemical methods to analyse the expression of both ferritin chains in the liver and kidney of 3-month and 2-year-old male and female Wistar rats. To see how sex hormones may affect expression we also studied adult animals gonadectomised at the age of 10 weeks. FtL and FtH were more expressed in both organs of female rats, while gonadectomy increased the expression in males and decreased it in females, which suggests that it is stimulated by female and inhibited by male steroid hormones. Normal kidney ferritin distribution and change with aging warrant more attention in studies of (patho) physiological and toxicological processes.


Assuntos
Apoferritinas , Ferritinas , Envelhecimento , Animais , Apoferritinas/metabolismo , Castração , Feminino , Ferritinas/metabolismo , Ferro , Rim/metabolismo , Fígado/metabolismo , Fígado/cirurgia , Masculino , Ratos , Ratos Wistar , Caracteres Sexuais
5.
Biomolecules ; 12(3)2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35327558

RESUMO

Ferritins are iron storage proteins assembled from 24 subunits into a spherical and hollow structure. The genomes of many bacteria harbor genes encoding two types of ferritin-like proteins, the bacterial ferritins (Ftn) and the bacterioferritins (Bfr), which bind heme. The genome of P. aeruginosa PAO1 (like the genomes of many bacteria) contains genes coding for two different types of ferritin-like molecules, ftnA (PA4235) and bfrB (PA3531). The reasons for requiring the presence of two distinct types of iron storage protein in bacterial cells have remained largely unexplained. Attempts to understand this issue in P. aeruginosa through the recombinant expression of the ftnA and bfrB genes in E. coli host cells, coupled to the biochemical and structural characterization of the recombinant 24-mer FtnA and 24-mer BfrB molecules, have shown that each of the recombinant molecules can form an Fe3+-mineral core. These observations led to the suggestion that 24-mer FtnA and 24-mer BfrB molecules coexist in P. aeruginosa cells where they share iron storage responsibilities. Herein, we demonstrate that P. aeruginosa utilizes a single heterooligomeric 24-mer Bfr assembled from FtnA and BfrB subunits. The relative content of the FtnA and BfrB subunits in Bfr depends on the O2 availability during cell culture, such that Bfr isolated from aerobically cultured P. aeruginosa is assembled from a majority of BfrB subunits. In contrast, when the cells are cultured in O2-limiting conditions, the proportion of FtnA subunits in the isolated Bfr increases significantly and can become the most abundant subunit. Despite the variability in the subunit composition of Bfr, the 24-mer assembly is consistently arranged from FtnA subunit dimers devoid of heme and BfrB subunit dimers each containing a heme molecule.


Assuntos
Escherichia coli , Pseudomonas aeruginosa , Proteínas de Bactérias/metabolismo , Grupo dos Citocromos b , Escherichia coli/genética , Escherichia coli/metabolismo , Ferritinas/metabolismo , Heme/metabolismo , Ferro/metabolismo , Oxigênio/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo
6.
Mol Metab ; 60: 101470, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35304332

RESUMO

BACKGROUND: With long-term metabolic malfunction, diabetes can cause serious damage to whole-body tissue and organs, resulting in a variety of complications. Therefore, it is particularly important to further explore the pathogenesis of diabetes complications and develop drugs for prevention and treatment. In recent years, different from apoptosis and necrosis, ferroptosis has been recognized as a new regulatory mode of cell death and involves the regulation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Evidence shows that ferroptosis and ferritinophagy play a significant role in the occurrence and development of diabetes complications. SCOPE OF REVIEW: we systematically review the current understanding of ferroptosis and ferritinophagy, focusing on their potential mechanisms, connection, and regulation, discuss their involvement in diabetes complications, and consider emerging therapeutic opportunities and the associated challenges with future prospects. MAJOR CONCLUSIONS: In summary, ferroptosis and ferritinophagy are worthy targets for the treatment of diabetes complications, but their complete molecular mechanism and pathophysiological process still require further study.


Assuntos
Complicações do Diabetes , Diabetes Mellitus , Ferroptose , Apoptose , Autofagia/fisiologia , Ferritinas/metabolismo , Humanos
7.
Food Chem ; 386: 132716, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35358860

RESUMO

Phytoferritin was explored as an attractive nanocarrier to encapsulate bioactive compounds due to its excellent stability and biocompatibility. In the present study, a novel phytoferritin derived from alfalfa (Medicago sativa) was successfully expressed, purified and characterized. Results confirmed that alfalfa ferritin, self-assembled by 24 subunits, formed a spherical hollow structure. Baicalein exhibits superior antioxidant properties and nutritious values, but low bioavailability and solubility limit its application. Herein, we fabricated water-soluble chitosan-ferritin-baicalein nanoparticles to overcome its drawbacks. It was calculated that one apoferritin cage could encapsulate 52 molecules of baicalein. Moreover, chitosan-ferritin-baicalein nanoparticles prolonged the release of baicalein in simulated gastrointestinal tract digestion. Caco-2 cell monolayer absorption analysis demonstrated that baicalein encapsulated within ferritin-chitosan double layers was more efficient in cellular transportation. These results indicated that alfalfa ferritin, as a novel cage-like protein, has potential application in improving the bioavailability of insoluble bioactive molecules.


Assuntos
Quitosana , Nanopartículas , Células CACO-2 , Quitosana/química , Digestão , Portadores de Fármacos/química , Ferritinas/metabolismo , Flavanonas , Humanos , Medicago sativa/metabolismo
8.
EMBO Rep ; 23(5): e54278, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35318808

RESUMO

Iron is not only essential but also a toxic trace element. Under iron repletion, ferritin maintains cellular iron homeostasis by storing iron to avoid iron toxicity. Under iron depletion, the ferritin-specific autophagy adaptor NCOA4 delivers ferritin to lysosomes via macroautophagy to enable cells to use stored iron. Here, we show that NCOA4 also plays crucial roles in the regulation of ferritin fate under iron repletion. NCOA4 forms insoluble condensates via multivalent interactions generated by the binding of iron to its intrinsically disordered region. This sequesters NCOA4 away from ferritin and allows ferritin accumulation in the early phase of iron repletion. Under prolonged iron repletion, NCOA4 condensates can deliver ferritin to lysosomes via a TAX1BP1-dependent non-canonical autophagy pathway, thereby preventing relative iron deficiency due to excessive iron storage and reduced iron uptake. Together, these observations suggest that the NCOA4-ferritin axis modulates intracellular iron homeostasis in accordance with cellular iron availability.


Assuntos
Ferritinas , Ferro , Autofagia/fisiologia , Ferritinas/genética , Ferritinas/metabolismo , Homeostase , Ferro/metabolismo , Lisossomos/metabolismo , Coativadores de Receptor Nuclear/genética , Fatores de Transcrição/metabolismo
9.
Clin Lab ; 68(3)2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35254032

RESUMO

BACKGROUND: ß-thalassemia is an inherited disorder that stems from a defect in beta-globin chain synthesis. Iron overload toxicity is one of the major clinical complications in ß-thalassemia that may be due to a reduction in the hepcidin level. As a result, intestinal iron absorption increases and finally iron overload occurs. The current study aimed to investigate the effect of curcumin on serum iron status, ferritin, and transferrin in patients with ß-thalas-semia intermedia. METHODS: This study was a randomized, controlled, double-blind clinical trial. Before and after the intervention period with curcumin, 5 ml blood was taken for the measurement of the entire index related to iron status. RESULTS: Our results demonstrated the levels of serum iron (p-value < 0.001), ferritin (p-value = 0.002), and transferrin saturation (p-value < 0.001) significantly decreased in the curcumin group compared to placebo. CONCLUSIONS: The data presented in this article show that curcumin supplementation would be effective in alleviating iron overload in patients with ß-thalassemia intermedia.


Assuntos
Curcumina , Sobrecarga de Ferro , Talassemia beta , Curcumina/uso terapêutico , Método Duplo-Cego , Ferritinas/metabolismo , Humanos , Ferro/metabolismo , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/metabolismo , Talassemia beta/complicações , Talassemia beta/tratamento farmacológico , Talassemia beta/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-35240430

RESUMO

INTRODUCTION: Ferritin is the major iron-storage glycoprotein found in all tissues. Ferritin glycosylation can be assessed by the differential affinities of ferritin glycoforms for Concanavalin A (ConA), a lectin. The fraction of serum ferritin bound to ConA is called "glycosylated ferritin" (GF). Low GF reflects macrophagic activation and is an essential biomarker used in adult-onset Still's disease (AOSD), macrophage activation syndrome (MAS) and Gaucher disease diagnosis and therapeutic management. To date, no complete assay description and method validation according to the ISO 15189 standard has been published. This study aimed to describe and validate our method used for GF measurement and describe GF values observed in patients. MATERIALS AND METHODS: Ferritin glycoforms were separated based on their affinities for ConA using commercially available TRIS-barbital buffer, Sepharose and ConA/Sepharose 4B gels. Ferritin concentrations were measured on the Siemens Dimension Vista 1500®. We analysed 16,843 GF values obtained between 2000 and 2021 from our database of patients. RESULTS: Optimal separation of ferritin glycoforms was obtained by 15-min incubation of serum with ConA/Sepharose at pH 8. The optimized volume were 0.4 mL for total serum ferritin (TSF) 30-1000 µg/L and 0.5 mL for TSF 1000-2500 µg/L. Serum with higher TSF should be pre-diluted in the TRIS-barbital buffer. Reproducibility of ferritin measurement in the TRIS-barbital buffer matrix was excellent (intra-assay CV < 1%; inter-assay CV < 4%). Reproducibility of GF assay was good (intra-assay CV < 10% for low and high ferritin samples, respectively; and inter-assay CV < 10%). Inter-operator variability was 21.6% for GF < 20%. Ferritin was stable for up to 3 days in the TRIS-barbital buffer. An inter-laboratory exchange program conducted with another French hospital showed good agreement between results. In our database, <20% GF levels were scarce, compatible with the low prevalence of Still's disease, MAS, and Gaucher disease. The 95% confidence interval for GF was [26-58]%, lower than values described in the literature for healthy individuals. CONCLUSION: Thanks to good performances, this technique can become readily available for laboratories servicing patients with AOSD, MAS (including severe COVID-19 patients) and Gaucher disease patients.


Assuntos
Técnicas de Química Analítica/métodos , Concanavalina A/metabolismo , Ferritinas/sangue , Síndrome de Ativação Macrofágica/sangue , Doença de Still de Início Tardio/sangue , Biomarcadores/sangue , Biomarcadores/metabolismo , Ferritinas/metabolismo , Doença de Gaucher/sangue , Doença de Gaucher/metabolismo , Humanos , Síndrome de Ativação Macrofágica/metabolismo , Ligação Proteica , Doença de Still de Início Tardio/metabolismo
11.
Cells ; 11(6)2022 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-35326435

RESUMO

Elemental iron is an indispensable prosthetic group of DNA replication relative enzymes. The upregulation of ferritin translation by iron regulatory proteins (IRP1) in host cells is a nutritional immune strategy to sequester available iron to pathogens. The efficient replication of Ostreid herpesvirus 1 (OsHV-1), a lethal dsDNA virus among bivalves, depends on available iron. OsHV-1 infection was found to trigger iron limitation in ark clams; however, it is still an enigma how OsHV-1 successfully conducted rapid replication, escaping host iron limitations. In this study, we identified the IRP1 protein (designated as SbIRP-1) in the ark clam (Scapharca broughtonii) and found it could bind to the iron-responsive element (IRE) of ferritin (SbFn) mRNA based on electrophoretic mobility shift assay (EMSA). Knockdown of SbIRP-1 expression (0.24 ± 1.82-fold of that in NC group, p < 0.01) by RNA interference resulted in the accumulation of SbFn in hemocytes (1.79 ± 0.01-fold, p < 0.01) post-24 h of enhanced RNA interference injection. During OsHV-1 infection, SbFn mRNA was significantly upregulated in hemocytes from 24 h to 60 h, while its protein level was significantly reduced from 24 h to 48 h, with the lowest value at 36 h post-infection (0.11 ± 0.01-fold, p < 0.01). Further analysis by RNA immunoprecipitation assays showed that OsHV-1 could enhance the binding of SbIRP-1 with the SbFn IRE, which was significantly increased (2.17 ± 0.25-fold, p < 0.01) at 36 h post-infection. Consistently, SbIRP-1 protein expression was significantly increased in hemocytes from 12 h to 48 h post OsHV-1 infection (p < 0.01). In conclusion, the results suggest that OsHV-1 infection could suppress post-transcriptional translation of SbFn through the regulation of SbIRP-1, which likely contributes to OsHV-1 evasion of SbFn-mediating host iron limitation.


Assuntos
Scapharca , Animais , Ferritinas/genética , Ferritinas/metabolismo , Ferro/metabolismo , Proteína 1 Reguladora do Ferro/metabolismo , RNA Mensageiro/genética , Scapharca/genética
12.
ACS Nano ; 16(3): 4175-4185, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35167250

RESUMO

Sperm motility can be enhanced by adding ATP exogenously during in vitro fertilization. However, administering exogenous ATP to the testis to improve sperm motility for in vivo asthenozoospermia treatment has not been investigated yet. Inspired by the recent advances in nanomedicine, we investigated whether the capability of drug delivery nanocarriers to traverse the blood-testis barrier (BTB) can facilitate ATP-dependent asthenozoospermia treatment. We found that the human H-ferritin (HFn) nanocarrier possesses the capability to traverse the BTB and specifically targets the head of elongated sperm cells. Specifically, the HFn nanocarrier traversed the BTB and accumulated in the sperm heads by binding with the HFn receptor (HFR), whose expression was relatively low in Sertoli cells but high in sperm heads. In a gossypol-induced mouse asthenozoospermia model, the administration of an ATP-loaded HFn nanocage through a tail vein injection significantly improved sperm motility. Moreover, the HFn nanocarrier was not toxic to mice in the short (1d) and long terms (30d, 90d) nor did it affect their reproductive health. Thus, the ATP-loaded HFn nanocarrier can potentially serve as a drug-delivery system for treating asthenozoospermia.


Assuntos
Astenozoospermia , Trifosfato de Adenosina/metabolismo , Animais , Apoferritinas/metabolismo , Astenozoospermia/tratamento farmacológico , Astenozoospermia/metabolismo , Barreira Hematotesticular/metabolismo , Ferritinas/metabolismo , Humanos , Masculino , Camundongos , Motilidade Espermática , Espermatozoides/metabolismo
13.
Int J Mol Sci ; 23(3)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35162949

RESUMO

Despite advances in the management of iron deficiency in heart failure (HF), the mechanisms underlying the effects of treatment remain to be established. Iron distribution and metabolism in HF pathogenesis need to be clarified. We used a porcine tachycardia-induced cardiomyopathy model to find out how HF development influences hepatic and myocardial iron storing, focusing on ferritin, the main iron storage protein. We found that cumulative liver congestion (due to the decrease of heart function) overwhelms its capacity to recycle iron from erythrocytes. As a consequence, iron is trapped in the liver as poorly mobilized hemosiderin. What is more, the ferritin-bound Fe3+ (reflecting bioavailable iron stores), and assembled ferritin (reflecting ability to store iron) are decreased in HF progression in the liver. We demonstrate that while HF pigs show iron deficiency indices, erythropoiesis is enhanced. Renin-angiotensin-aldosterone system activation and hepatic hepcidin suppression might indicate stress erythropoiesisinduced in HF. Furthermore, assembled ferritin increases but ferritin-bound Fe3+ is reduced in myocardium, indicating that a failing heart increases the iron storage reserve but iron deficiency leads to a drop in myocardial iron stores. Together, HF in pigs leads to down-regulated iron bioavailability and reduced hepatic iron storage making iron unavailable for systemic/cardiac needs.


Assuntos
Insuficiência Cardíaca/metabolismo , Hemossiderina/metabolismo , Fígado/metabolismo , Taquicardia/complicações , Animais , Modelos Animais de Doenças , Ferritinas/metabolismo , Humanos , Ferro/metabolismo , Masculino , Sistema Renina-Angiotensina , Suínos , Taquicardia/etiologia , Taquicardia/metabolismo
14.
Int J Mol Sci ; 23(4)2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35216492

RESUMO

A major hallmark of Parkinson's disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates. A triad contribution of α-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated α-synuclein inhibits SNARE protein complexes and destabilizes microtubules to halt vesicular trafficking systems, including that of autophagy effectively. The scope of this review is to describe the physiological and pathological relationship between iron regulation and α-synuclein, providing a detailed understanding of iron metabolism within nigral neurons. The underlying mechanisms of autophagy and ferritinophagy are explored in the context of PD, identifying potential therapeutic targets for future investigation.


Assuntos
Autofagia/fisiologia , Ferritinas/metabolismo , Ferro/metabolismo , Doença de Parkinson/metabolismo , alfa-Sinucleína/metabolismo , Animais , Humanos
15.
Int J Mol Sci ; 23(3)2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35162984

RESUMO

Iron accumulates in the ageing brain and in brains with neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Down syndrome (DS) dementia. However, the mechanisms of iron deposition and regional selectivity in the brain are ill-understood. The identification of several proteins that are involved in iron homeostasis, transport, and regulation suggests avenues to explore their function in neurodegenerative diseases. To uncover the molecular mechanisms underlying this association, we investigated the distribution and expression of these key iron proteins in brain tissues of patients with AD, DS, PD, and compared them with age-matched controls. Ferritin is an iron storage protein that is deposited in senile plaques in the AD and DS brain, as well as in neuromelanin-containing neurons in the Lewy bodies in PD brain. The transporter of ferrous iron, Divalent metal protein 1 (DMT1), was observed solely in the capillary endothelium and in astrocytes close to the ventricles with unchanged expression in PD. The principal iron transporter, ferroportin, is strikingly reduced in the AD brain compared to age-matched controls. Extensive blood vessel damage in the basal ganglia and deposition of punctate ferritin heavy chain (FTH) and hepcidin were found in the caudate and putamen within striosomes/matrix in both PD and DS brains. We suggest that downregulation of ferroportin could be a key reason for iron mismanagement through disruption of cellular entry and exit pathways of the endothelium. Membrane damage and subsequent impairment of ferroportin and hepcidin causes oxidative stress that contributes to neurodegeneration seen in DS, AD, and in PD subjects. We further propose that a lack of ferritin contributes to neurodegeneration as a consequence of failure to export toxic metals from the cortex in AD/DS and from the substantia nigra and caudate/putamen in PD brain.


Assuntos
Doença de Alzheimer , Síndrome de Down , Doenças Neurodegenerativas , Doença de Parkinson , Agregados Proteicos , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Proteínas de Transporte de Cátions , Síndrome de Down/complicações , Síndrome de Down/metabolismo , Ferritinas/metabolismo , Hepcidinas/metabolismo , Humanos , Ferro/metabolismo , Doenças Neurodegenerativas/metabolismo , Doença de Parkinson/metabolismo
16.
Adv Healthc Mater ; 11(8): e2101715, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34997700

RESUMO

Methods that leverage bone marrow mesenchymal stem cells (BMSCs) and stimulating factor kartogenin (KGN) for chondrocyte differentiation have paved the way for cartilage repair. However, the scarce carriers for efficiently bridging the two components significantly impede their further application. Therefore, one kind of bifunctional ferritin has designed and synthesized: RC-Fn, a genetically engineered ferritin nanocage with RGD peptide and WYRGRL peptide on the surface. The RGD can target the integrin αvß3 of BMSCs and promote proliferation, and the WYRGRL peptide has an inherent affinity for the cartilage matrix component of collagen II protein. RC-Fn nanocages have an ideal size for penetrating the proteoglycan network of cartilage. Thus, intra-articularly injected RC-Fn with KGN loading can convert the articular cavity from a barrier into a reservoir to prevent rapid release and clearance of KGN and exogenous BMSCs, which results in efficient and persistent chondrogenesis in cartilage regeneration.


Assuntos
Condrogênese , Células-Tronco Mesenquimais , Anilidas , Cartilagem/metabolismo , Diferenciação Celular , Ferritinas/metabolismo , Ácidos Ftálicos
17.
Int J Mol Sci ; 23(1)2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35008961

RESUMO

Mitochondrial ferritin (FtMt) is a mitochondrial iron storage protein associated with neurodegenerative diseases. In patients with progressive supranuclear palsy (PSP), FtMt was shown to accumulate in nigral neurons. Here, we investigated FtMt and LC3 in the post-mortem midbrain of PSP patients to reveal novel aspects of the pathology. Immunohistochemistry was used to assess the distribution and abnormal changes in FtMt and LC3 immunoreactivities. Colocalization analysis using double immunofluorescence was performed, and subcellular patterns were examined using 3D imaging and modeling. In the substantia nigra pars compacta (SNc), strong FtMt-IR and LC3-IR were observed in the neurons of PSP patients. In other midbrain regions, such as the superior colliculus, the FtMt-IR and LC3-IR remained unchanged. In the SNc, nigral neurons were categorized into four patterns based on subcellular LC3/FtMt immunofluorescence intensities, degree of colocalization, and subcellular overlapping. This categorization suggested that concomitant accumulation of LC3/FtMt is related to mitophagy processes. Using the LC3-IR to stage neuronal damage, we retraced LC3/FtMt patterns and revealed the progression of FtMt accumulation in nigral neurons. Informed by these findings, we proposed a hypothesis to explain the function of FtMt during PSP progression.


Assuntos
Ferritinas/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Mitocondriais/metabolismo , Neurônios/metabolismo , Substância Negra/metabolismo , Paralisia Supranuclear Progressiva/metabolismo , Biomarcadores , Suscetibilidade a Doenças , Ferritinas/genética , Imunofluorescência , Humanos , Imuno-Histoquímica , Mesencéfalo/metabolismo , Mesencéfalo/patologia , Proteínas Associadas aos Microtúbulos/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Mitofagia , Ligação Proteica , Transporte Proteico , Substância Negra/patologia , Paralisia Supranuclear Progressiva/diagnóstico , Paralisia Supranuclear Progressiva/etiologia
18.
FEBS Open Bio ; 12(3): 664-674, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35090095

RESUMO

Ferritin is considered to be an ubiquitous and conserved iron-binding protein that plays a crucial role in iron storage, detoxification, and immune response. Although ferritin is of critical importance for almost all kingdoms of life, there is a lack of knowledge about its role in the marine invertebrate sea cucumber (Apostichopus japonicus). In this study, we characterized the first crystal structure of A. japonicus ferritin (AjFER) at 2.75 Å resolution. The structure of AjFER shows a 4-3-2 symmetry cage-like hollow shell composed of 24 subunits, mostly similar to the structural characteristics of other known ferritin species, including the conserved ferroxidase center and 3-fold channel. The 3-fold channel consisting of three 3-fold negative amino acid rings suggests a potential pathway in which metal ions can be first captured by Asp120 from the outside environment, attracted by His116 and Cys128 when entering the channel, and then transferred by Glu138 from the 3-fold channel to the ferroxidase site. Overall, the presented crystal structure of AjFER may provide insights into the potential mechanism of the metal transport pathway for related marine invertebrate ferritins.


Assuntos
Pepinos-do-Mar , Stichopus , Animais , Cristalografia , Ferritinas/química , Ferritinas/metabolismo , Invertebrados/metabolismo , Pepinos-do-Mar/metabolismo , Stichopus/metabolismo
19.
Langmuir ; 38(3): 1106-1113, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35015545

RESUMO

Ferritin is a spherical cage-like protein that is useful for loading large functional particles for various applications. To our knowledge, how pH affects the interfaces inside ferritin and the mechanism of ferritin disassembly is far from complete. For this article, we conducted a series of molecular dynamics simulations (MD) at different pH values to study how interfaces affect ferritins' stability. It is shown that dimers are stable even at extremely low pH (pH 2.0), indicating that the dimer is the essential subunit for disassembly, and the slight swelling of the dimer resulting from monomer rotation inside a dimer is what triggers disassembly. During ferritin disassembly, there are two types of interfaces involved, and the interface between dimers is crucial. We also found that the driving forces for maintaining dimer stability are different when a dimer is inside ferritin and in an acidic solution. At low pH, the protonation of residues can lead to the loss of the salt bridge and the hydrogen bond between dimers, resulting in the disassembly of ferritin in an acidic environment. The above simulations reveal the possible mechanism of ferritin disassembly in an acidic solution, which can help us to design innovative and functional ferritin cages for different applications.


Assuntos
Ferritinas , Simulação de Dinâmica Molecular , Ferritinas/metabolismo , Ligação de Hidrogênio
20.
Microb Biotechnol ; 15(5): 1525-1541, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34644442

RESUMO

Ferritin proteins have an enormous capacity to store iron in cells. In search for the best conditions to accumulate and store bioavailable iron, we made use of a double mutant null for the monothiol glutaredoxins GRX3 and GRX4. The strain grx3grx4 accumulates high iron concentrations in the cytoplasm, making the metal easily available for ferritin chelation. Here, we perform a comparative study between human (L and H) and soya bean ferritins (H1 and H2) function in the eukaryotic system Saccharomyces cerevisiae. We demonstrate that the four human and soya bean ferritin chains are successfully expressed in our model system. Upon coexpression of either both human or soya bean ferritin chains, respiratory conditions along with iron supplementation led us to obtain the maximum yields of iron stored in yeast described to date. Human and soya bean ferritin chains are functional and present equivalent properties as promoters of cell survival in iron overload conditions. The best system revealed that the four human and soya bean ferritins possess a novel function as anti-ageing proteins in conditions of iron excess. In this respect, both ferritin chains with oxidoreductase capacity (human-H and soya bean-H2) bear the highest capacity to extend life suggesting the possibility of an evolutionary conservation.


Assuntos
Fabaceae , Proteínas de Saccharomyces cerevisiae , Saccharomycetales , Ferritinas/genética , Ferritinas/metabolismo , Humanos , Ferro/metabolismo , Oxirredutases/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...