更新于：2024-09-19

CYBRD1

更新于：2024-09-19

基本信息

别名

CYB561A2、CYBRD1、cytochrome b reductase 1

+ [6]

简介

Plasma membrane reductase that uses cytoplasmic ascorbate as an electron donor to reduce extracellular Fe(3+) into Fe(2+) (PubMed:30272000). Probably functions in dietary iron absorption at the brush border of duodenal enterocytes by producing Fe(2+), the divalent form of iron that can be transported into enterocytes (PubMed:30272000). It is also able to reduce extracellular monodehydro-L-ascorbate and may be involved in extracellular ascorbate regeneration by erythrocytes in blood (PubMed:17068337). May also act as a ferrireductase in airway epithelial cells (Probable). May also function as a cupric transmembrane reductase (By similarity).

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100 项与 CYBRD1 相关的临床结果

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100 项与 CYBRD1 相关的转化医学

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0 项与 CYBRD1 相关的专利（医药）

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213

项与 CYBRD1 相关的文献（医药）

2024-08-21·Journal of the American Chemical Society

All “Roads” Lead to Rocksalt Structure

Article

作者: Chen, Helen ; Stevanovic, Vladan ; Novick, Andrew ; Stevanović, Vladan ; Chen, Helen ; Jankousky, Matthew ; Novick, Andrew

Rocksalt is the most common crystal structure among binary compounds. Moreover, no long-lived, metastable polymorphs are observed in compounds with the rocksalt ground state. We investigate the absence of polymorphism via first-principles random structure sampling and transformation kinetics modeling of three rocksalt compounds: MgO, TaC, and PbTe. Random structure sampling reveals that for all three systems the rocksalt basin of attraction covers much more of configuration space than any other, making it statistically the most significant structure. The kinetics modeling shows that virtually all other relevant structures, including most of the 457 known A₁B₁ prototypes, transform rapidly to rocksalt, making it the only option at ambient conditions. These results explain the absence of polymorphism in binary rocksalts, answer why rocksalt is the structure of choice for high-entropy ceramics and disordered ternary nitrides, and help understand/predict metastable states in crystalline solids more generally.

2024-07-01·Archives of Microbiology

Direct and macrophage stimulation mediated effects of active, inactive, and cell-free supernatant forms of Akkermansia muciniphila and Faecalibacterium duncaniae on hepcidin gene expression in HepG2 cells

Article

作者: Rohani, Pejman ; Khatami, Shohreh ; Masotti, Andrea ; Irian, Saeed ; Siadat, Seyed Davar ; Ahmadi Badi, Sara ; Malek, Amin ; Bereimipour, Ahmad ; Sohouli, Mohammad Hassan ; Shojaie, Shima ; Seyedi, Seyed Amirhesam

Hepcidin is a crucial regulator of iron homeostasis with protective effects on liver fibrosis. Additionally, gut microbiota can also affect liver fibrosis and iron metabolism. Although the hepatoprotective potential of Akkermansia muciniphila and Faecalibacterium duncaniae, formerly known as F. prausnitzii, has been reported, however, their effects on hepcidin expression remain unknown. We investigated the direct and macrophage stimulation-mediated effects of active, heat-inactivated, and cell-free supernatant (CFS) forms of A. muciniphila and F. duncaniae on hepcidin expression in HepG2 cells by RT-qPCR analysis. Following stimulation of phorbol-12-myristate-13-acetate (PMA) -differentiated THP-1 cells with A. muciniphila and F. duncaniae, IL-6 concentration was assessed via ELISA. Additionally, the resulting supernatant was treated with HepG2 cells to evaluate the effect of macrophage stimulation on hepcidin gene expression. The expression of genes mediating iron absorption and export was also examined in HepG2 and Caco-2 cells via RT-qPCR. All forms of F. duncaniae increased hepcidin expression while active and heat-inactivated/CFS forms of A. muciniphila upregulated and downregulated its expression, respectively. Active, heat-inactivated, and CFS forms of A. muciniphila and F. duncaniae upregulated hepcidin expression, consistent with the elevation of IL-6 released from THP-1-stimulated cells as a macrophage stimulation effect in HepG2 cells. A. muciniphila and F. duncaniae in active, inactive, and CFS forms altered the expression of hepatocyte and intestinal iron-mediated absorption /exporter genes, namely dcytb and dmt1, and fpn in HepG2 and Caco-2 cells, respectively. In conclusion, A. muciniphila and F. duncaniae affect not only directly but also through macrophage stimulation the expression of hepcidin gene in HepG2 cells. These findings underscore the potential of A. muciniphila and F. duncaniae as a potential therapeutic target for liver fibrosis by modulating hepcidin and intestinal and hepatocyte iron metabolism mediated gene expression.

2024-04-01·animal

Influence of copper source and dietary inclusion level on growth performance of weaned pigs and expression of trace element related genes in the small intestine

Article

作者: van Baal, J ; Kruijt, L ; Bikker, P ; Romeo, A ; Durosoy, S ; Binnendijk, G P

Copper is routinely supplemented to weanling pig diets at concentrations above nutritional requirements to enhance growth performance. We hypothesised that this effect depends on the source of Cu and its dietary concentration. We tested this in weaned pigs (26 d of age) over a 35-d period using a 2 × 3 factorial arrangement with two Cu-sources (CuSO₄ and Cu₂O, monovalent copper oxide, CoRouge®) and three supplementary dietary Cu-levels (15, 80 and 160 mg Cu/kg) as respective factors. Increasing Cu level linearly increased (P < 0.001) final BW and daily gain. These effects tended (P = 0.09) to be greater with Cu₂O than CuSO₄. Feed conversion ratio decreased linearly (P < 0.001) with increasing dietary Cu content, independent of Cu source. Plasma Cu, Zn and Fe levels were unaffected, whereas liver Cu content increased quadratically (P < 0.001) with increasing dietary Cu content, with a larger increase (P < 0.001) with CuSO₄ than Cu₂O. Bile Cu content increased quadratically (P = 0.025) with increasing Cu content, irrespective of Cu source. RT-qPCR analysis revealed that increasing Cu content quadratically (P = 0.009) increased duodenal but not ileal metallothionein 1A (MT1A) mRNA, with greater effect (P = 0.010) of CuSO₄. Regardless of the Cu source, increasing Cu dose linearly increased (P = 0.006) duodenal DMT1/SLC11A2 mRNA but decreased ZIP4/SLC39A4 mRNA in duodenum (P < 0.001) and ileum (P < 0.005). ZnT10/SLC30A10 mRNA was significantly (P = 0.021) and numerically (P = 0.061) greater with Cu₂O compared to CuSO₄, in duodenum and ileum, respectively. Copper content quadratically modulated duodenal but not ileal transferrin receptor (P = 0.029) and ferric reductase CYBRD1 mRNA (P = 0.022). In hypothalamus, high Cu dose (P = 0.024) and Cu₂O as source (P = 0.028) reduced corticotropin-releasing hormone (CRH) mRNA. Low versus high CuSO₄ increased corticotropin-releasing hormone receptor (CRHR2) mRNA, while low Cu₂O had the opposite effect (P = 0.009). In conclusion, incremental Cu intake enhanced growth performance, with a tendency for a greater effect of Cu₂O. The lower increase in duodenal MT1A mRNA and liver Cu content indicates that less Cu from Cu₂O was absorbed by gut and sequestered in liver. Thus, high Cu absorption is not essential for its growth-promoting effect and dietary Cu may affect intestinal Fe and Zn absorption via the active, transcellular route. The effects on hypothalamic CRH and CRHR2 expression indicate a role for the hypothalamus in mediating the effects of Cu on growth performance.

项与 CYBRD1 相关的新闻（医药）

2024-01-11

·Science Daily

A new type of plant metalloreductase maintains root growth under low phosphorus

Phosphorus is essential for undisturbed plant growth and development. However, in many soils, phosphorus is only poorly available. One mechanism used by plants to increase phosphorus availability is the release of malate, an organic acid, which can form complexes with iron or aluminium in the soil, thereby liberating sorbed phosphate. However, this response can also result in iron overaccumulation, which can inhibit root growth. The release of low-molecular weight carboxylates, such as malate, is used by many plant species to mine poorly available phosphorus (P) from the soil. Malate can increase the availability of phosphate, the P form taken up by plants, by chelating trivalent aluminium or iron (Fe). Work in the last years has demonstrated that the accumulation of Fe(III)-malate complexes in the apoplast of root tips attenuates root growth under low-P conditions because the now soluble Fe(III) (ferric Fe) participates in reactions leading to oxidative stress. However, how root tips cope with this increased ferric Fe availability has remained elusive as all currently known ferric reductases, which are required for Fe uptake, are repressed in response to P deficiency or not expressed in root tips. "By searching for other potential ferric reductases among P deficiency-induced genes, we found a previously uncharacterized gene encoding a domain predicted to participate in ferric reduction," explains Dr. Ricardo Giehl, co-leader of IPK's research group "Molecular Plant Nutrition." "When we disrupted this gene, Fe over accumulated in root tips and root growth under low P was even more severely inhibited." The gene was, therefore, named HYPERSENSITIVE TO LOW P1 (HYP1). HYP1 is a member of the CYBDOM family and possesses a cytochrome b561 domain, which is common in several ferric reductases active in animal cells, such as the duodenal cytochrome b (Dcytb) involved with dietary Fe uptake in humans. "Although CYBDOMs are ubiquitous in several organisms and come typically as large families in plants, their function in any organism is still poorly understood," explains Rodolfo Maniero, first author of the study. Using AlphaFold-supported modeling and site-directed mutagenesis, the researchers found that HYP1 can coordinate three b-hemes, which are critical for the protein's activity. Electrophysiological characterization of HYP1 in oocytes revealed that the protein can transport electrons derived from ascorbate (vitamin C) across the plasma membrane. Acceptors of these electrons are Fe(III) and Cu(II) (cupric ion), indicating that the protein is a metalloreductase. "Regarding the ferric reductase activity of HYP1, our results demonstrate that this function is critical to prevent malate-induced Fe overaccumulation in the apoplast and to maintain cell elongation and meristem integrity in root tips exposed to low P," explains Dr. Ricardo Giehl. "Our results also suggested that an Fe-uptake mechanism is active in root tips, where the well-known ferric reductase FRO2 and the Fe(II) transporter IRT1 are not present," says the IPK scientist. "Our study not only shed light on the physiological roles of CYBDOMs but also identified a new target to improve root growth under limiting-P conditions."

2023-08-15

·生物谷

谢黎炜/印遇龙团队系统总结铁元素在肠道菌群稳态和宿主健康中的作用机理

综上所述，肠道菌群、铁稳态和宿主健康三个因素之间的相互影响和制约非常复杂，仍需要深入研究和理解。然而，这种平衡对于维持宿主的健康至关重要。近期，广东省科学院微生物研究所、华南应用微生物国家重点实验室、肠道微生态与健康团队谢黎炜研究员，联合中国科学院亚热带农业生态研究所的印遇龙院士和万丹博士，在 SCIENCE CHINA-Life Sciences 期刊发表了题为：Gut microbiota bridges the iron homeostasis and host health 的综述文章。该综述系统性地总结了铁元素在肠道菌群稳态以及宿主健康中的作用机理。肠腔内的肠道菌群通过分解肠道内容物产生多种次级代谢产物。其中，一些较为突出的有益产物包括发酵纤维素产生的短链脂肪酸族（SCFAs）、多种支链氨基酸（BCAA）以及次级胆汁酸等。这些代谢物能够通过肠道上皮和肠道免疫系统在菌群影响下分泌的免疫因子，进入循环系统并到达宿主各个组织和器官，发挥相应作用。然而，肠道菌群中同时存在一些对宿主有害或机会型致病菌的菌种。这些菌种的代谢物或存在本身对宿主健康不利，例如LPS、细菌毒素等产物能够直接导致宿主疾病。在肠道菌群中，各个菌群组分之间又存在竞争关系。在有害菌群占优势的情况下，有益菌群代谢物的减少也会导致宿主的各个器官或系统受到不利影响。因此，肠道菌群与宿主器官之间的交互调节机制被称为“肠-轴”。“肠-轴”连接肠道菌群和宿主生理和病理，建立了紧密的联系，在并且在疾病的发生和发展过程中扮演了重要的角色（图1）。图1：“肠-轴”介导肠道菌群与器官/系统交互调节 “肠-轴”相关的疾病包括代谢性综合征、消化系统、神经系统和免疫系统疾病等。这些疾病通常与肠道菌群紊乱后特定代谢产物的增减密切相关，例如SCFAs。这些代谢产物是肠道菌群与宿主器官和系统互作的重要媒介，同时也是肠道免疫细胞的重要营养物质。这些代谢产物的变化能够通过直接或间接的途径对宿主各个系统健康造成影响，持续的积累会导致器官发生病变。作为肠道菌群稳态调控和宿主健康之间的重要联系节点，铁稳态的重要性毋庸置疑。宿主铁稳态失衡会导致多种疾病，肠道及腔内容物所构成的肠道铁环境对肠道菌群的组成和动态平衡也具有重要影响。食物是哺乳动物主要的铁源。在经过肠道上皮细胞上的Dcytb还原和DMT1吸收后，铁元素通过FPN1进入循环系统，并以与转铁蛋白（Transferrin，Trf）结合的形式转运。这些铁元素大部分被红细胞以血红蛋白的形式储存和携带，其余部分被细胞用于构建线粒体电子传递链或以铁蛋白的形式储存在细胞中。铁在细胞中的氧化还原反应是其发挥功能的关键，但铁稳态被破坏后，会引起组织器官功能受损。铁缺乏通常会导致缺铁性贫血、循环系统障碍以及肠道相关疾病。而铁过量则会导致细胞脂质过氧化，破坏膜性细胞器，从而引发器官功能损伤。铁稳态失衡与多种铁代谢相关疾病有关，如帕金森综合征、结肠癌、肌萎缩等。此外，铁稳态失衡也与代谢性疾病如非酒精性脂肪肝、肥胖和二型糖尿病密切相关（图2）。图2：系统铁稳态和疾病发生于发展