更新于：2024-05-01

Nramp2

solute carrier family 11 member 2

更新于：2024-05-01

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-

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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1,449

项与 Nramp2 相关的文献（医药）

2024-02-14·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Targeting iron-metabolism:a potential therapeutic strategy for pulmonary fibrosis.

Review

作者: Yi Sun ; Yu Ren ; Li-Yun Song ; Yin-Ying Wang ; Tian-Gang Li ; Ying-Li Wu ; Li Li ; Zhong-Shan Yang

Iron homeostasisis is integral to normal physiological and biochemical processes of lungs. The maintenance of iron homeostasis involves the process of intake, storage and output, dependening on iron-regulated protein/iron response element system to operate tightly metabolism-related genes, including TFR1, DMT1, Fth, and FPN. Dysregulation of iron can lead to iron overload, which increases the virulence of microbial colonisers and the occurrence of oxidative stress, causing alveolar epithelial cells to undergo necrosis and apoptosis, and form extracellular matrix. Accumulated iron drive iron-dependent ferroptosis to exacerbated pulmonary fibrosis. Notably, the iron chelator deferoxamine and the lipophilic antioxidant ferritin-1 have been shown to attenuate ferroptosis and inhibit lipid peroxidation in pulmonary fibrosis. The paper summarises the regulatory mechanisms of dysregulated iron metabolism and ferroptosis in the development of pulmonary fibrosis. Targeting iron metabolism may be a potential therapeutic strategy for the prevention and treatment of pulmonary fibrosis.

2024-02-14·Clinical science (London, England : 1979)

Tetramethylpyrazine attenuates renal tubular epithelial cell ferroptosis in contrast-induced nephropathy by inhibiting transferrin receptor and intracellular reactive oxygen species.

Article

作者: Zhongqiang Zhu ; Jun Li ; Zhiyong Zhi Song ; Tonglu Tong Li ; Zongping Zong Li ; Xuezhong Gong

Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury (AKI). Recently ferroptosis was reported to be crucial for AKI pathogenesis. Our previous studies indicated antioxidant tetramethylpyrazine (TMP) prevent CIN in vivo. However, whether ferroptosis is involved in TMP nephroprotective mechanism against CIN is unclear. In present study we investigated the role of renal tubular epithelial cell ferroptosis in TMP reno-protective effect against CIN and the molecular mechanisms by which TMP regulates ferroptosis. Classical contrast-medium Iohexol was used to construct CIN models in rats and HK-2 cells. Results showed tubular cell injury was accompanied by ferroptosis both in vivo and in vitro, including the typical features of ferroptosis, Fe2+ accumulation, lipid peroxidation and decreased glutathione peroxidase 4 (GPX4). Ferroptosis inhibition by classic inhibitors Fer-1 and DFO promoted cell viability and reduced intracellular ROS production. Additionally, TMP significantly inhibited renal dysfunction, reduced AKI biomarkers, prevented ROS production, inhibited renal Fe2+ accumulation and increased GPX4 expression. Expressions of various proteins associated with iron ion metabolism, including transferrin receptor (TFRC), divalent metal transporter 1, iron-responsive element binding protein 2, ferritin heavy chain 1, ferroportin 1, and heat shock factor binding protein 1, were examined using mechanistic analyses. Among these, TFRC changes were the most significant after TMP pretreatment. Results of siRNA knockdown and plasmid overexpression of TFRC indicated TFRC is essential for TMP to alleviate ferroptosis and reduce LDH release, Fe2+ accumulation and intracellular ROS. Our findings provide crucial insights about the potential of TMP in treating AKI associated with ferroptosis.

2024-02-12·Journal of agricultural and food chemistry

Gum Arabic-Derived Hydroxyproline-Rich Peptides Stimulate Intestinal Nonheme Iron Absorption via HIF2α-Dependent Upregulation of Iron Transport Proteins.

Article

作者: Shiyang Li ; Wenshuo Xing ; Yuxin Gang ; Meichao Zhang ; Zifang Zhao ; Haohao Wu ; Suqin Zhu

The stimulation of host iron absorption is a promising antianemia strategy adjunctive/alternative to iron intervention. Here, gum arabic (GA) containing 3.14 ± 0.56% hydroxyproline-rich protein with repetitive X-(Pro/Hyp)_n motifs was found to increase iron reduction, uptake, and transport to upregulate duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferroportin, and hephaestin to inhibit hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) and to stabilize HIF2α in polarized Caco-2 cell monolayers in a dose-dependent manner, and this was dependent on its protein fraction, rather than the polysaccharide fraction. Three abundant GA-derived hydroxyproline-containing dipeptides of Hyp-Hyp, Pro-Hyp, and Ser-Hyp were detected by liquid chromatography-mass spectrometry in the lysates of polarized Caco-2 cell monolayers at the maximum levels of  0.167 ± 0.021, 0.134 ± 0.017, and 0.089 ± 0.015 μg/mg of protein, respectively, and showed desirable docking affinity energy values of -7.53, - 7.91, and -7.39 kcal/mol, respectively, against human PHD3. GA-derived peptides also acutely increased duodenal HIF2α stability and Dcytb, DMT1, ferroportin, and hephaestin transcription in rats (P < 0.05). Overall, GA-derived hydroxyproline-rich peptides stimulated intestinal iron absorption via PHD inhibition, HIF2α stabilization, and subsequent upregulation of iron transport proteins.

项与 Nramp2 相关的新闻（医药）

2024-04-02

·PRNewswire

Alsana Appoints Eating Disorder Industry Veteran Allan Benham as CEO

WESTLAKE VILLAGE, Calif., April 2, 2024 /PRNewswire/ -- Allan Benham, BSN and MBA, a healthcare executive who specializes in leading organizations in the behavioral health treatment sector, has been appointed CEO of Alsana, an eating disorder recovery community. Benham has more than 20 years of experience in the healthcare industry. He most recently served as the chief operating officer (COO) and vice president of inpatient services with Meadows Behavioral Healthcare, a trauma, mental health, drug and alcohol addiction treatment, and eating disorder recovery program with 14 programs in seven states, with operations based in Arizona. In this role, he oversaw and led both inpatient and outpatient services while ensuring top-quality clinical care and regulatory compliance. "My passion for changing lives through recovery and for patients struggling with eating disorder behaviors patient aligns with Alsana's purpose: to provide compassionate, personalized treatment with a holistic approach, empowering people to embrace healing," said Benham. "I am excited to work closely with the professionals at Alsana to grow our in-person and virtual treatment programs to help more people across the nation achieve a long-lasting recovery." Prior to Benham's role as COO at Meadows Behavioral Healthcare, he was an executive director at the organization's Gentle Path at The Meadows, an addiction treatment center for men. He has also served as the executive director of Meadows Behavioral Healthcare's Remuda Ranch, their Eating Disorder program, and oversaw direct patient care as director of nursing and director of training and quality. A graduate of Chamberlain University College of Nursing in Addison, Il. with a Bachelor of Science in Nursing, Benham began his career as a Registered Nurse with Meadows Behavioral Health where he cared for patients with eating disorders. He also holds a Master of Business Administration from Grand Canyon University. 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

高管变更

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

微生物疗法

2023-05-06

·生物谷

Nature子刊：林爱福团队揭示LncRNA通过重编程铁代谢调控肿瘤进程

该研究发现，铁动态响应的 lncRNA LncRIM通过与Hippo通路上游节点分子NF2互作，抑制LATS1激酶活性，继而促进YAP下游铁代谢调控重要靶基因DMT1和TFR1表达，并通过放大LncR 细胞代谢重编程是恶性肿瘤的重要标志之一，识别和阻断肿瘤代谢进程重要调控途径业已成为肿瘤靶向治疗关注热点。目前研究表明，微量元素代谢异常在肿瘤发生发展中扮演重要角色，其中铁离子作为人体重要微量元素，参与包括DNA合成、氧运输和细胞呼吸链合成在内诸多生理活动，铁代谢失调与肿瘤发生发展密切相关。深入探究肿瘤细胞铁代谢节点分子调控事件，或将为恶性肿瘤临床干预提供新思路和新策略。