Last update 19 Sep 2024

Nramp2

Last update 19 Sep 2024

Basic Info

Synonyms

DCT1, Divalent cation transporter 1, Divalent metal transporter 1

+ [8]

Introduction

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.

Drugs associated with Nramp2

XEN602

Target

Nramp2

Mechanism

Nramp2 inhibitors

Active Org.

Xenon Pharmaceuticals, Inc.

Originator Org.

Xenon Pharmaceuticals, Inc.

Active Indication

Anemia, Hypochromic Microcytic, With Iron Overload

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

XEN-600 series (Xenon Pharmaceuticals)

Target

Nramp2

Mechanism

Nramp2 inhibitors

Active Org.-

Originator Org.

Xenon Pharmaceuticals, Inc.

Active Indication-

Inactive Indication

Beta-Thalassemia [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Nramp2

100 Translational Medicine associated with Nramp2

0 Patents (Medical) associated with Nramp2

1,491

Literatures (Medical) associated with Nramp2

31 Dec 2024·Gut Microbes

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

Article

Author: Nicolas, Gaël ; Canonne-Hergaux, François ; Humblot, Christèle ; Noordine, Marie-Louise ; Lefebvre, Thibaud ; 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.

01 Dec 2024·Journal of Ethnopharmacology

Benja-ummarit induces ferroptosis with cell ballooning feature through ROS and iron-dependent pathway in hepatocellular carcinoma

Article

Author: Erofeev, Alexander ; Maiuthed, Arnatchai ; Wichaiyo, Surasak ; Timoshenko, Roman ; Juntranggoor, Pichakorn ; Vaneev, Alexander ; Pradidarcheep, Wisuit ; Sandech, Nichawadee ; Savin, Nikita ; Yang, Meng Chieh ; Gorelkin, Petr ; Rukthong, Pattarawit

ETHNOPHARMACOLOGICAL RELEVANCEBenja-ummarit (BU), a traditional Thai herbal formula, has been prescribed by traditional Thai practitioners for the treatment of liver cancer. Clinical trials of BU have shown an increase in overall survival in hepatocellular carcinoma (HCC) patients, including stage 1-3 (with or without prior standard chemotherapy) and terminal stage. The clinical outcomes differ from those of other apoptosis-based conventional chemotherapies. The molecular mechanisms underlying the anti-cancer properties of BU remain unclear.AIM OF STUDYTo investigate BU-induced ferroptosis through morphological and molecular analyses of HCC cell lines and HCC rat tissues.METHODOLOGYCytotoxicity of BU extract in HepG2 and HuH-7 cells, with or without LX-2 in 2D and 3D cultures, was determined through MTT assay and by observing spheroid formation, respectively, as compared to sorafenib. Morphological changes and the cellular ultrastructure of the treated cells were evaluated by light microscopy and transmission electron microscopy (TEM), respectively. In addition, alterations in ferroptosis protein markers in both cell lines and rat liver tissue were determined using western blot analysis and immunohistochemical staining, respectively. To investigate the pathways mediating ferroptosis, cells were pretreated with an iron chelator to confirm the iron-dependent ferroptosis induced by the BU extract. Intracellular ROS, a mediator of ferroptosis, was measured using a scanning ion conductance microscope (SICM). SICM was also used to determine cellular stiffness. The lipid profiles of BU-treated cells were studied using LC-MS/MS.RESULTSThe BU extract induced cell death under all HCC cell culture conditions. The BU-IC₅₀ in HepG2 and HuH-7 were 31.24 ± 4.46 μg/mL and 23.35 ± 0.27 μg/mL, respectively as determined by MTT assay. In co-culture with LX-2, BU exhibited a similar trend of cytotoxicity in both HepG2 and HuH-7 cells. Light microscopy showed cell ballooning features with intact plasma membranes, and TEM microscopy showed mitochondrial swelling and reduced mitochondrial cristae in BU-treated cells. BU promotes intracellular iron levels by increasing DMT1 and NCOA4 expression and decreasing FTH1 expression. BU also suppressed the cellular antioxidant system by lowering CD98, NRF2, and GPX4 expression, and promoting KEAP1 expression. IHC results of HCC rat liver tissues showed the absence of DMT1 and high expression of GPX4 in the tumor area. Pre-treatment with an iron chelator partially restored cell viability and shifted the mode of cell death to a more apoptosis-like morphology in the BU-treated group. The SICM showed increased intracellular ROS levels and cellular stiffness 24 h after BU treatment. In more detail of BU-mediated ferroptosis, cellular lipid profiling revealed increased expression of 3 polyunsaturated lipids, which are highly susceptible to lipid peroxidation, in BU-treated cells.DISCUSSIONAlterations in intracellular iron levels, ROS levels, and cellular lipid composition have been previously reported in cancer cells. Therefore, targeting the iron-dependent ROS pathway and polyunsaturated lipids via BU-induced ferroptosis may be more cancer-specific than apoptosis-based cancer drugs. These observations are in accordance with the clinical outcomes of BU. The ferroptosis-inducing mechanism of BU makes it an extremely promising novel drug candidate for the treatment of HCC.

01 Dec 2024·Genes & Nutrition

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

Article

Author: 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.

News (Medical) associated with Nramp2

01 Aug 2024

·www.prnewswire.com

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

Clinical Result

10 Jul 2024

·www.prnewswire.com

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

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