更新于：2024-11-01

Nramp2

更新于：2024-11-01

基本信息

别名

DCT1、Divalent cation transporter 1、Divalent metal transporter 1

+ [8]

简介

Proton-coupled metal ion symporter operating with a proton to metal ion stoichiometry of 1:1 (PubMed:17109629, PubMed:22736759, PubMed:25491917, PubMed:17293870, PubMed:25326704). Selectively transports various divalent metal cations, in decreasing affinity: Cd(2+) > Fe(2+) > Co(2+), Mn(2+) >> Zn(2+), Ni(2+), VO(2+) (PubMed:17109629, PubMed:22736759, PubMed:25491917, PubMed:17293870, PubMed:25326704). Essential for maintenance of iron homeostasis by modulating intestinal absorption of dietary Fe(2+) and TF-associated endosomal Fe(2+) transport in erythroid precursors and other cells (By similarity). Enables Fe(2+) and Mn(2+) ion entry into mitochondria, and is thus expected to promote mitochondrial heme synthesis, iron-sulfur cluster biogenesis and antioxidant defense (PubMed:24448823) (By similarity). Can mediate uncoupled fluxes of either protons or metal ions.

关联

项与 Nramp2 相关的药物

XEN602

靶点

Nramp2

作用机制

Nramp2抑制剂

在研机构

Xenon Pharmaceuticals, Inc.

原研机构

Xenon Pharmaceuticals, Inc.

在研适应症

小细胞低色素性贫血伴铁过载

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

XEN-600 series (Xenon Pharmaceuticals)

靶点

Nramp2

作用机制

Nramp2抑制剂

在研机构-

原研机构

Xenon Pharmaceuticals, Inc.

在研适应症-

非在研适应症

β地中海贫血 [+1]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 Nramp2 相关的临床结果

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100 项与 Nramp2 相关的转化医学

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0 项与 Nramp2 相关的专利（医药）

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1,509

项与 Nramp2 相关的文献（医药）

2025-01-01·Nutrition

Influence of supplementation with probiotic bacteria Lactiplantibacillus plantarum and Latilactobacillus curvatus on selected parameters of duodenum iron metabolism in rats on a high-fat, iron-deficient diet

Article

作者: Skrypnik, Katarzyna ; Suliburska, Joanna ; Mikołajczyk-Stecyna, Joanna ; Olejnik-Schmidt, Agnieszka ; Schmidt, Marcin

OBJECTIVESA high-fat, iron (Fe)-deficient Western diet induces obesity and dysregulates Fe metabolism. We compared the influence of Lactiplantibacillus plantarum and Latilactobacillus curvatus with and without Fe supplementation on duodenal Fe uptake under high-fat diet conditions.METHODSRats were fed a high-fat diet (HF group) or high-fat, Fe-deficient diet (HFDEF group) or control diet (C group) for 8 wk. For the next 8 wk, the rats in the C and HF groups continued on the same diet, whereas the rats in the HFDEF group were divided into six groups and fed high-fat, Fe-deficient diet combinations with L. plantarum (Lp), L. curvatus (Lc), and Fe supplementation (HFDEF, HFDEFFe, HFDEFLp, HFDEFLc, HFDEFFeLp, HFDEFFeLc). Duodenum and serum samples were collected for analysis.RESULTSIn the duodenum, the Fe content was higher in the HFDEFFeLp and HFDEFFeLc groups; the ferroportin level was higher in the HFDEFFeLp and HFDEFFeLc groups versus the HF group; the divalent metal transporter 1 level was higher in the HFDEFFeLc group versus the C and HF groups; and duodenal cytochrome B was higher in the HFDEFLc versus all the other groups. In addition, duodenal expression of the solute carrier family 11 member 2 gene was higher in the HFDEF group versus the C, HF, HFDEFFe, HFDEFFeLp, and HFDEFFeLc groups; that of the TFRC gene was higher in the HFDEFFeLc group versus the C, HF, HFDEF, and HFDEFFe groups; and that of the HJV gene was higher in the HFDEFFeLp group versus the C, HF, HFDEF, HFDEFFe, and HFDEFLc groups.CONCLUSIONSL. plantarum and L. curvatus supplementation shows some potential to enhance duodenal cellular Fe uptake in rats on a high-fat, Fe-deficient diet.

2024-12-31·Gut Microbes

The microbiota and the host organism switch between cooperation and competition based on dietary iron levels

Article

作者: Nicolas, Gaël ; Humblot, Christèle ; Lefebvre, Thibaud ; Noordine, Marie-Louise ; Canonne-Hergaux, François ; Bruneau, Aurélia ; Baye, Kaleab ; Seyoum, Yohannes ; Cherbuy, Claire ; Thomas, Muriel

The microbiota significantly impacts digestive epithelium functionality, especially in nutrient processing. Given the importance of iron for both the host and the microbiota, we hypothesized that host-microbiota interactions fluctuate with dietary iron levels. We compared germ-free (GF) and conventional mice (SPF) fed iron-containing (65 mg/Kg) or iron-depleted (<6 mg/Kg) diets. The efficacy of iron privation was validated by iron blood parameters. Ferritin and Dmt1, which represent cellular iron storage and transport respectively, were studied in tissues where they are abundant: the duodenum, liver and lung. When the mice were fed an iron-rich diet, the microbiota increased blood hemoglobin and hepcidin and the intestinal ferritin levels, suggesting that the microbiota helps iron storage. When iron was limiting, the microbiota inhibited the expression of the intestinal Dmt1 transporter, likely via the pathway triggered by Hif-2α. The microbiota assists the host in storing intestinal iron when it is abundant and competes with the host by inhibiting Dmt1 in conditions of iron scarcity. Comparison between duodenum, liver and lung indicates organ-specific responses to microbiota and iron availability. Iron depletion induced temporal changes in microbiota composition and activity, reduced α-diversity of microbiota, and led to Lactobacillaceae becoming particularly more abundant after 60 days of privation. By inoculating GF mice with a simplified bacterial mixture, we show that the iron-depleted host favors the gut fitness of Bifidobacterium longum.

2024-12-01·Genes & Nutrition

Dysfunction of DMT1 and miR-135b in the gut-testis axis in high-fat diet male mice

Article

作者: Ye, Yun ; Zhou, Lin ; Qi, Jia ; Cao, Wenbin ; Ding, Ruike ; Xue, Ying ; Zhang, Yulin ; Deng, Lijun ; Zhang, Yanru ; Liu, Enqi

AbstractBackgroundObese patients have been found to be susceptible to iron deficiency, and malabsorption of dietary iron is the cause of obesity-related iron deficiency (ORID). Divalent metal transporter 1 (DMT1) and ferroportin (FPN), are two transmembrane transporter proteins expressed in the duodenum that are closely associated with iron absorption. However, there have been few studies on the association between these two proteins and the increased susceptibility to iron deficiency in obese patients. Chronic inflammation is also thought to be a cause of obesity-related iron deficiency, and both conditions can have an impact on spermatogenesis and impair male reproductive function. Based on previous studies, transgenerational epigenetic inheritance through gametes was observed in obesity.ResultsOur results showed that obese mice had decreased blood iron levels (p < 0.01), lower protein and mRNA expression for duodenal DMT1 (p < 0.05), but no statistically significant variation in mRNA expression for duodenal FPN (p > 0.05); there was an increase in sperm miR-135b expression (p < 0.05). Bioinformatics revealed ninety overlapping genes and further analysis showed that they were primarily responsible for epithelial cilium movement, fatty acid beta-oxidation, protein dephosphorylation, fertilization, and glutamine transport, which are closely related to spermatogenesis, sperm development, and sperm viability in mice.ConclusionsIn obese mice, we observed downregulation of DMT1 in the duodenum and upregulation of miR-135b in the spermatozoa.

项与 Nramp2 相关的新闻（医药）

2024-08-01

·PRNewswire

Alsana's New 2023 Treatment Outcomes Report Reveals Virtual Treatment Success and Extraordinary Patient Care Results

Data demonstrates patient desire for virtual treatment and power of Adaptive Care Model® in reducing eating disorder symptoms ST. LOUIS, Aug. 1, 2024 /PRNewswire/ -- Alsana, an eating disorder recovery community, released its 2023 Treatment Outcomes Report, revealing that 91% of clients reported virtual treatment options provided comprehensive and adaptive care. Alsana's ongoing Perception of Care (PoC) and treatment outcomes survey identifies opportunities for improvement and provides patients the chance to reflect on their care experience. Of the clients enrolled in virtual treatment, 97% said they "would recommend Alsana to others in need of treatment." Furthermore, 97% of those who identify as LGBTQ+ described Alsana as an accepting and affirming environment, while 99% reported that their sexual and gender identity was affirmed by the clinical team. "Eating disorders are a festering mental health condition that don't just affect one's physical body, but also quality of life and mental state," said Allan Benham, CEO of Alsana. "Our clinical team is comprised of professionals who use the Adaptive Care Model® to approach the body, mind and soul for holistic healing. Alsana's in-person or virtual treatment journey utilizes the power of community and connection to support patients every step of the way for sustained recovery." The 2023 Eating Disorder Examination Questionnaire (EDE-Q), which surveyed respondents located at in-person treatment programs, features substantial data supporting the efficacy of eating disorder treatment, affirming care and positive treatment outcomes and reviews. The 2023 results demonstrated significant improvement in eating disorder symptoms (with a large effect size of .415). This measurement quantifies eating disorder symptom changes from admission to discharge. Among the Treatment Outcomes Report measurements, clients saw the most improvement in their quality of life, reporting statistically significant improvement before and after treatment with the largest effect size of .481. Other positive outcomes found in the report include improvements in anxiety, depression and trauma related symptoms, emotion regulation, and the compulsive exercise test. Alsana offers in-person Residential and PHP/IOP programs in Alabama, California and Missouri as well as thriving virtual programs across the U.S. For more information on Alsana's in-person or virtual treatment options or support services, visit Alsana.com. Alsana's full 2023 outcomes report is available for download here. About Alsana® Alsana is an eating recovery community with virtual Partial Hospitalization (PHP) and Intensive Outpatient (IOP) programs across the United States, in addition to Residential, PHP/IOP programs in Alabama, California, and Missouri. Its eating disorder treatment programs are compassion-focused, evidence-based, and designed in alignment with Alsana's Adaptive Care Model®. This whole-person approach addresses healing in all areas of clients' lives by integrating medical, nutritional, and therapeutic care with movement and relational therapies. Alsana serves adult clients of all genders and sexual identities struggling with a broad spectrum of eating, feeding, and co-occurring mental health conditions. Alsana's programs accommodate the unique needs of vegan clients and clients struggling with ED-DMT1, also known as "diabulimia." Learn more at . SOURCE Alsana

临床结果

2024-07-10

·PRNewswire

Alsana Enhances Eating Disorder Treatment Options with Multi-Level Care Campus in Birmingham

Clients transition seamlessly between Residential and Day Treatment in the new comprehensive, supportive environment. BIRMINGHAM, Ala., July 10, 2024 /PRNewswire/ -- Alsana, an eating disorder recovery community, has incorporated Partial Hospitalization (PHP) and Intensive Outpatient (IOP) treatments into its residential treatment program in Birmingham, AL. The integration of these treatments enables those with eating disorders to remain in the same location as their needs change during their recovery and healing process. According to a study from the Harvard T.H. Chan School of Public Health, 9% of Alabama residents, or roughly 430,271 people, will develop an eating disorder in their lifetime. It's one of the deadliest mental health conditions second only to opioid addiction. Knowing the signs is key to getting early treatment, which can lead to a lasting recovery. "Our Birmingham campus provides in-patient and out-patient clients with three levels of care in a nurturing and inclusive residential environment," said Mary Elizabeth Akinaka, LPC, CEDS-S, Regional Executive Director with Alsana. "We meet our clients where they are in their recovery journey - our local in-person programs allow them stay close to home for the added support and comfort during treatment." The Birmingham campus features: A serene and scenic healing location in Birmingham's rolling hills Access to a continuum of high-quality early intervention treatment, along with inpatient and outpatient care featuring clinical, nutritional, and medical support in one centralized location Adaptable programs that consider each adult's needs and schedules to help them return to their families, school and jobs Click here for additional information about Alsana's Birmingham campus. About Alsana® Alsana is an eating recovery community with virtual Partial Hospitalization (PHP) and Intensive Outpatient (IOP) programs across the United States, in addition to Residential, PHP/IOP programs in Alabama, California, and Missouri. Its eating disorder treatment program are compassion-focused, evidence-based, and designed in alignment with Alsana's Adaptive Care Model®. This whole-person approach addresses healing in all areas of clients' lives by integrating medical, nutritional, and therapeutic care with movement and relational therapies. Alsana serves adult clients of all genders and sexual identities struggling with a broad spectrum of eating, feeding, and co-occurring mental health conditions. Alsana's programs accommodate the unique needs of vegan clients and clients struggling with ED-DMT1, also known as "diabulimia." Learn more at . SOURCE Alsana

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