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121.
    
Human ferritin H-chain protein (FTH1)-based nanoparticles possess a precisely assembled nanometer-scale structure and high safety. However, their applications for imaging and drug delivery towards cancer cells remain limited due to a lack of target specificity. Epidermal growth factor receptor (EGFR) is overexpressed in many malignant tissues including breast cancer, and has been used as a therapeutic target for cancer treatment. Herein, a genetic method is shown to generate EGF-FTH1 chimeric proteins. EGF-FTH1 nanoparticles with EGF on the surface are then produced. The data demonstrate that EGF-FTH1 nanoparticles, with a small size (11.8 ± 1.8 nm), narrow size distribution, and high biosafety, can specifically bind to and then be taken up by breast cancer MCF-7 cells and MDA-MB-231 cells, but not normal breast epithelial MCF-10A cells. In contrast, binding and absorption of nontargeted ferritin-based nanoparticles to breast cancer cells are negligible. In vivo studies show that EGF-FTH1 nanoparticles are accumulated in breast tumors in a mouse xenograft model. Interestingly, the concentration of EGF-FTH1 nanoparticles in the tumor site is significantly reduced when mice are pretreated with an excess of free EGF. These results imply that EGF-EGFR interaction plays an important role in regulating the tumor retention of EGF-FTH1 nanoparticles.  相似文献   
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To study the feasibility of promoting iron absorption by peptides derived from α-lactalbumin and β-lactoglobulin, the present work examined the transport of iron across Caco-2 monolayer cell as in vitro model. Caco-2 cells were seeded in bicameral chambers with α-lactalbumin hydrolysate-Fe (α-LAH-Fe) complex and β-lactoglobulin hydrolysate-Fe (β-LGH-Fe) complex, α-LAH and iron mixture, β-LGH and iron mixture, FeSO4 and ascorbic acid mixture, and FeSO4. In addition, the cytotoxicity of α-LAH-Fe and β-LGH-Fe complexes were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The iron absorption and ferritin content were assessed using the coupled in vitro digestion/Caco-2 cell model. Results support that peptide-iron complexes can promote ferritin formation and it is possible to apply β-LGH-Fe complexes as iron-fortified supplements with high iron absorbability.  相似文献   
124.
    
Ferritins are ubiquitous iron storage proteins where Fe(II) sequestration prevents not only its spontaneous oxidation to Fe(III) but also production of toxic free radicals. Recently, scientists have subverted these nature functions and used ferritin cage structures of nanometer dimensions for encapsulation of guest molecules such as anti‐cancer drugs or bioactive nutrients based on pH induced ferritin disassembly and reassembly property. However, prior to this study, ferritin nanocage was required to disassemble only under harsh pH conditions (≤2.0 or ≥11.0), followed by reassembly at near neutral pH. Such harsh conditions can cause protein or guest molecules damage to a great extent during this pH‐induced unfolding–refolding process. Here, we provide evidence demonstrating that the apoferritin shell is flexible rather than rigid. Indeed, we found that two large complex molecules, uranyl acetate dihydrate and phosphotungstic acid, can reach the cavity of both plant and animal apoferritin followed by mineralization. Moreover, large organic compound such as curcumin and doxorubicin can also be encapsulated within ferritin cavity by its mixing with protein. This strategy will increase the use of ferritin in nanotechnology, and could be also applicable to other shell‐like proteins as templates to prepare nanomaterials.  相似文献   
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We report herein a novel mechanism, unraveled by proteomics and validated by in vitro and in vivo studies, of the aberrant aging-associated upregulation of ovarian transferrin and ferritin in rat ovaries. The ovarian mass and serum estradiol titer plummeted while the ovarian labile ferrous iron and total iron levels escalated with age in rats. Oxidative stress markers, such as nitrite/nitrate, 3-nitrotyrosine, and 4-hydroxy-2-nonenal, accumulated in the aging ovaries due to an aberrant upregulation of the ovarian transferrin, ferritin light/heavy chains, and iron regulatory protein 2(IRP2)-mediated transferrin receptor 1 (TfR1). Ferritin inhibited estradiol biosynthesis in ovarian granulosa cells in vitro via the upregulation of a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p65/p50-induced oxidative and inflammatory factor inducible nitric oxide synthase (iNOS). An in vivo study demonstrated how the age-associated activation of NF-κB induced the upregulation of iNOS and the tumor necrosis factor α (TNFα). The downregulation of the keap1-mediated nuclear factor erythroid 2-related factor 2 (Nrf2), that induced a decrease in glutathione peroxidase 4 (GPX4), was observed. The aberrant transferrin and ferritin upregulation triggered an iron accumulation via the upregulation of an IRP2-induced TfR1. This culminates in NF-κB-iNOS-mediated ovarian oxi-inflamm-aging and serum estradiol decrement in naturally aging rats. The iron accumulation and the effect on ferroptosis-related proteins including the GPX4, TfR1, Nrf2, Keap1, and ferritin heavy chain, as in testicular ferroptosis, indicated the triggering of ferroptosis. In young rats, an intraovarian injection of an adenovirus, which expressed iron regulatory proteins, upregulated the ovarian NF-κB/iNOS and downregulated the GPX4. These novel findings have contributed to a prompt translational research on the ovarian aging-associated iron metabolism and aging-associated ovarian diseases.  相似文献   
126.
    
Auranofin (AF), a gold(I) compound that is currently used for the treatment of rheumatoid arthritis and is in clinical trials for its promising anticancer activity, was encapsulated within the human H-chain and the horse spleen ferritin nanocages using the alkaline disassembly/reassembly protocol. The aim of the work was to highlight possible differences in their drug loading capacity and efficacy. The drug-loaded ferritins were characterized via UV-vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy to assess AF encapsulation and to define the exact amount of gold atoms trapped in the Ft cavity. The crystal structures allowed us to define the nature of AF interaction with both ferritins and to identify the gold binding sites. Moreover, the biological characterization let us to obtain preliminary information on the cytotoxic effect of AF when bound to the human H-chain.  相似文献   
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With iron at its core, the tetrapyrrole heme ring is a cardinal prosthetic group made up of many proteins that participate in a wide array of cellular functions and metabolism. Once released, due to its pro-oxidant properties, free heme in sufficient amounts can result in injurious effects to the kidney and other organs. Heme oxygenase-1 (HO-1) has evolved to promptly attend to such injurious potential by facilitating degradation of heme into equimolar amounts of carbon monoxide, iron, and biliverdin. HO-1 induction is a beneficial response to tissue injury in diverse animal models of diseases, including those that affect the kidney. These protective attributes are mainly due to: (i) prompt degradation of heme leading to restraining potential hazardous effects of free heme, and (ii) generation of byproducts that along with induction of ferritin have proven beneficial in a number of pathological conditions. This review will focus on describing clinical aspects of some of the conditions with the unifying end-result of increased heme burden and will discuss the molecular mechanisms that ensue to protect the kidneys.  相似文献   
129.
铁蛋白(ferritin)是一种广泛存在于动物、植物和微生物中的多亚基笼形结构蛋白,具有调节体内铁代谢平衡的功能,同时可以保护细胞免受因各种环境胁迫而导致的细胞氧化损伤.近年来,随着研究的深入,铁蛋白独特的纳米笼形结构以及特殊的理化性质使其成为一种具有广泛应用前景的新型蛋白质纳米载体材料.文章对铁蛋白的分子结构和功能进...  相似文献   
130.
High hydrostatic pressure (HHP) has drawn considerable attention because of its potential application in food industry. Ferritin, an iron storage protein, is widely distributed in food made from legume seeds, which is highly stable due to its shell-like structure. Therefore, it is of special interest to know whether or not high HHP treatment has effect on this protein. In this study, the structure and activity of soybean seed ferritin (SSF) were examined by circular dichroism spectrum (CD), UV–VIS and fluorescence spectrophotometry in conjunction with stopped-flow light scattering upon treatment with HHP at 400 MPa for 10 min. Results revealed that such treatment has little effect on the primary and secondary structure of SSF, but pronouncedly altered its tertiary and quaternary structure. As a result, the protein aggregation property and iron release activity were dramatically changed, while its activity of iron oxidative deposition was kept unchanged.  相似文献   
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