FOOD RESEARCH INTERNATIONAL
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2024
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IF 7
Xiangjun Ding,Mengdan Xu,Haili Li,Xueling Li,Meiqing Li
There is an increasing amount of research into the development of a third generation of iron supplementation using peptide-iron chelates. Peptides isolated from mung bean were chelated with ferrous iron (MBP-Fe) and tested as a supplement in mice suffering from iron-deficiency anemia (IDA). Mice were randomly divided into seven groups: a group fed the normal diet, the IDA model group, and IDA groups treated with inorganic iron (FeSO 4 ), organic iron (ferrous bisglycinate, Gly-Fe), low-dose MBP-Fe(L-MBP-Fe), high-dose MBP-Fe(H-MBP-Fe), and MBP mixed with FeSO 4 (MBP/Fe). The different iron supplements were fed for 28 days via intragastric administration. The results showed that MBP-Fe and MBP/Fe had ameliorative effects, restoring hemoglobin (HGB), red blood cell (RBC), hematocrit (HCT), and serum iron (SI) levels as well as total iron binding capacity (TIBC) and body weight gain of the IDA mice to normal levels. Compared to the inorganic (FeSO 4 ) and organic (Gly-Fe) iron treatments, the spleen coefficient and damage to liver and spleen tissues were significantly lower in the H-MBP-Fe and MBP/Fe mixture groups, with reparative effects on jejunal tissue. Gene expression analysis of the iron transporters Dmt 1 ( Divalent metal transporter 1 ), Fpn 1 ( Ferroportin 1 ), and Dcytb ( Duodenal cytochrome b ) indicated that MBP promoted iron uptake. These findings suggest that mung bean peptide-ferrous chelate has potential as a peptide-based dietary supplement for treating iron deficiency.
研究领域:
营养学
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分子生物学
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食品科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
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2023
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IF 5.4
Yang Wang,Na Ling,Yaping Wang,Dexin Ou,Zhao Liang,Guoqing Li,Hongyuan Zhao,Yingwang Ye
Cronobacter sakazakii ( C. sakazakii ) is a common food-borne pathogen that induces meningitis, sepsis, and necrotizing enterocolitis, primarily in newborns and infants. Iron plays a pivotal role in the growth of cells and biofilm formation. However, the effects of hemin (ferric ion donor) on C. sakazakii cells are scarcely known. Here, we explored the effect of ferric ions on the growth of planktonic C. sakazakii , biofilm formation, and swarming motility by crystal violet staining (CVS), scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and swarming assay. Our study demonstrated that ferric ions facilitated the growth of planktonic C. sakazakii , while hemin at concentrations ranging from 50 to 800 μmol/L promoted biofilm formation and at concentrations between 50 and 200 μmol/L enhanced the swarming motility of C. sakazakii . Furthermore, high hemin concentrations (400–800 μmol/L) were found to reduce flagellar length, as confirmed by transmission electron microscopy (TEM). These findings indicated that ferric ions mediated the swarming motility of C. sakazakii by regulating flagellar assembly. Finally, transcriptomic analysis of C. sakazakii was performed at hemin concentrations of 0, 50, and 200 μmol/L, which revealed that several genes associated with iron transport and metabolism, and flagellar assembly were essential for the survival of C. sakazakii under hemin treatment. Our findings revealed the molecular basis of ferric ions on C. sakazakii growth and biofilm formation, thus providing a novel perspective for its prevention and control.
研究领域:
微生物学
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食品安全
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分子生物学
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DOI
PubMed
高影响因子
EMBO REPORTS
·
2021
·Vol. 22
·期 2
·e51162
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IF 8.807
Jia Song,Tongtong Liu,Yue Yin,Wei Zhao,Zhiqiang Lin,Yuxin Yin,Dan Lu,Fuping You
Although iron is required for cell proliferation, iron-dependent programmed cell death serves as a critical barrier to tumor growth and metastasis. Emerging evidence suggests that iron-mediated lipid oxidation also facilitates immune eradication of cancer. However, the regulatory mechanisms of iron metabolism in cancer remain unclear. Here we identify OTUD1 as the deubiquitinase of iron-responsive element-binding protein 2 (IREB2), selectively reduced in colorectal cancer. Clinically, downregulation of OTUD1 is highly correlated with poor outcome of cancer. Mechanistically, OTUD1 promotes transferrin receptor protein 1 (TFRC)-mediated iron transportation through deubiquitinating and stabilizing IREB2, leading to increased ROS generation and ferroptosis. Moreover, the presence of OTUD1 promotes the release of damage-associated molecular patterns (DAMPs), which in turn recruits the leukocytes and strengthens host immune response. Reciprocally, depletion of OTUD1 limits tumor-reactive T-cell accumulation and exacerbates colon cancer progression. Our data demonstrate that OTUD1 plays a stimulatory role in iron transportation and highlight the importance of OTUD1-IREB2-TFRC signaling axis in host antitumor immunity.
研究领域:
癌症生物学
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免疫学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Nature Communications
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2024
·Vol. 15
·期 1
·1-13
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IF 14.7
Li Huihui,Cui Yanmei,Hu Yule,Zhao Mengran,Li Kuanyu,Pang Xiaoyun,Sun Fei,Zhou Bing
Iron is a potent biochemical, and accurate homeostatic control is orchestrated by a network of interacting players at multiple levels. Although our understanding of organismal iron homeostasis has advanced, intracellular iron homeostasis is poorly understood, including coordination between organelles and iron export into the ER/Golgi. Here, we show that SLC39A13 (ZIP13), previously identified as a zinc transporter, promotes intracellular iron transport and reduces intracellular iron levels. ZIP13 loss causes an iron deficiency in the ER/Golgi and other intracellular compartments, such as lysosomes and mitochondria, as well as elevating iron in the cytosol. ZIP13 overexpression has the opposite effect, increasing iron in organellar compartments. We suggest that ZIP13 gatekeeps an iron trafficking route that shunts iron from the cytosol to the ER/Golgi hub. Zip13- knockout male mice have iron deposition in several tissues. These data demonstrate that mammalian ZIP13 is crucial for iron homeostasis and suggest a potential iron transport function.
研究领域:
细胞生物学
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分子生物学
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铁代谢
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营养生物化学
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DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Huali Lei,Guanghui Hou,Lin Liu,Zifan Pei,Youdong Chen,Yujie Lu,Nalin Yang,Shumin Sun,Liang Cheng
Iron metabolism has emerged as a promising target for cancer therapy; however, the innate metabolic compensatory capacity of cancer cells significantly limits the effectiveness of iron metabolism therapy. Herein, bioactive gallium sulfide nanodots (GaSx), with dual functions of “reprogramming” and “interfering” iron metabolic pathways, were successfully developed for tumor iron metabolism therapy. The constructed GaSx nanodots ingeniously harness hydrogen sulfide (H2S) gas, which is released in response to the tumor microenvironment, to reprogram the inherent transferrin receptor 1 (TfR1)-ferroportin 1 (FPN1) iron metabolism axis in cancer cells. Concurrently, the gallium ions (Ga3+) derived from GaSx act as a biochemical “Trojan horse”, mimicking the role of iron and displacing it from essential biomolecular binding sites, thereby influencing the fate of cancer cells. By leveraging the dual mechanisms of Ga3+-mediated iron disruption and H2S-facilitated reprogramming of iron metabolic pathways, GaSx prompted the initiation of a paraptosis–apoptosis hybrid pathway in cancer cells, leading to marked suppression of tumor proliferation. Importantly, the dysregulation of iron metabolism induced by GaSx notably increased tumor cell susceptibility to both chemotherapy and immune checkpoint blockade (ICB) therapy. This study underscores the therapeutic promise of gas-based interventions and metal ion interference strategies for the tumor metabolism treatment.
研究领域:
癌症生物学
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纳米技术
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药理学
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治疗学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2024
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IF 5.3
Ting Li,Yangge Du,Hantao Yao,Boxuan Zhao,Zijun Wang,Rourong Chen,Yaoting Ji,Minquan Du
As bone-resorbing cells rich in mitochondria, osteoclasts require high iron uptake to promote mitochondrial biogenesis and maintain a high-energy metabolic state for active bone resorption. Given that abnormal osteoclast formation and activation leads to imbalanced bone remodeling and osteolytic bone loss, osteoclasts may be crucial targets for treating osteolytic diseases such as periodontitis. Isobavachin (IBA), a natural flavonoid compound, has been confirmed to be an inhibitor of receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation from bone marrow-derived macrophages (BMMs). However, its effects on periodontitis-induced bone loss and the potential mechanism of its anti-osteoclastogenesis effect remain unclear. Our study demonstrated that IBA suppressed RANKL-induced osteoclastogenesis in BMMs and RAW264.7 cells and inhibited osteoclast-mediated bone resorption in vitro. Transcriptomic analysis indicated that iron homeostasis and reactive oxygen species (ROS) metabolic process were enriched among the differentially expressed genes following IBA treatment. IBA exerted its anti-osteoclastogenesis effect by inhibiting iron accumulation in osteoclasts. Mechanistically, IBA attenuated iron accumulation in RANKL-induced osteoclasts by inhibiting the mitogen-activated protein kinase (MAPK) pathway to upregulate ferroportin1 (Fpn1) expression and promote Fpn1-mediated intracellular iron efflux. We also found that IBA inhibited mitochondrial biogenesis and function, and reduced RANKL-induced ROS generation in osteoclasts. Furthermore, IBA attenuated periodontitis-induced bone loss by reducing osteoclastogenesis in vivo. Overall, these results suggest that IBA may serve as a promising therapeutic strategy for bone diseases characterized by osteoclastic bone resorption.
研究领域:
药理学
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牙科
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
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IF 6.1
Sen Wang,Hui Ren,Chen Fan,Qian Lin,Man Liu,Jun Tian
Mycotoxin ochratoxin A (OTA) is a critical food safety concern due to its nephron-toxic effects and is detected in a wide range of food and feedstuffs. OTA nephrotoxicity is related to oxidative stress and damage. However, the mediator(s) of the excessive oxidative stress is unclear. The current study used human kidney cell lines to investigate whether and how intracellular iron contributed to OTA-induced ROS accumulation and how OTA-induced iron-dependent ferroptotic cell death. Our results showed that OTA treatment affected the cell viability and induced the typical characteristics of cell ferroptosis. Furthermore, gene and protein expression results indicated that OTA disrupted iron homeostasis by upregulating the expression levels of iron importer TFR1 and FTH, while downregulating the expression level of iron exporter FPN and dramatically increasing its negative regulator Hepcidin. The changes were consistent with the induction of intracellular iron accumulation and elevated levels of oxidative stress and lipid peroxidation. Additionally, co-treatment with OTA and an iron chelator significantly improved cell viability, reduced cellular total iron and ROS, and reversed OTA-induced changes in iron metabolism gene expression levels. Interestingly, the addition of a ROS scavenger also reversed cell death and changes in mRNA and protein expression levels of iron metabolism genes but to a lesser degree than that of the iron-chelating agent. Our results revealed that OTA induced ferroptosis in renal cells by disrupting iron homeostasis and increasing ROS.
研究领域:
毒理学
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细胞生物学
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食品安全
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2020
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IF 6.17
Kang Han,Xiaofang Jin,Xin Guo,Guoli Cao,Siyu Tian,Yiming Song,Yuanyuan Zuo,Peng Yu,Guofen Gao,Yan-Zhong Chang
The transcription factor NF-E2-related factor 2 (Nrf2) is a central regulator of cellular antioxidant and detoxification response. The association between Nrf2 activity and iron-related oxidative stress in neurodegenerative diseases has been studied, and Nrf2 was found to transcriptionally regulate the expression of iron transporters and ferroptosis-related factors. However, the role of Nrf2 in age-related motor dysfunction and its link to iron metabolism dysregulation in brain have not been fully elucidated. In this study, with different ages of Nrf2 knockout (KO) and wild type (WT) mice, we investigated the effects of Nrf2 deficiency on brain oxidative stress, iron metabolism and the motor coordination ability of mice. In contrast to the predicted neuroprotective role of Nrf2 in oxidative stress-related diseases , we found that Nrf2 KO remarkably improved the motor coordination of aged mice, which was associated with the reduced ROS level and decreased apoptosis of dopaminergic neurons in substantia nigra (SN) of 18-month-old Nrf2 KO mice . With high-iron and Parkinson's disease (PD) mouse models, we revealed that Nrf2 KO prevented the deposition of brain iron, particularly in SN and striatum, which may subsequently delay motor dysfunction in aged mice. The regulation of Nrf2 KO on brain iron metabolism was likely mediated by decreasing the ferroportin 1 (FPN1) level on brain microvascular endothelial cells , thus hindering the process of iron entry into the brain. Nrf2 may be a potential therapeutic target in age-related motor dysfunction diseases for its role in regulating brain iron homeostasis .
研究领域:
神经科学
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分子生物学
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衰老研究
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-23
·
IF 12.6
Yang Yang,Lv Mingzhu,Liu Ruihong,Yu Peilu,Shen Ziyi,Bai Dazhang,Zhao Peilin,Yang Jin,Tang Xiaoping,Yang Hanfeng,Yong Yuan,Jiang Guohui
Background Intracerebral haemorrhage (ICH) is a devastating neurological disorder with high morbidity and mortality rates, largely owing to the lack of effective therapeutic strategies. Growing evidence has underscored the pivotal role of ferroptosis in intracerebral haemorrhage, and its contribution to neuronal death and exacerbation of brain injury, thus establishing it as a crucial target for therapeutic intervention. In recent years, polyoxometalate nanoclusters (NCs) have been applied in various neurodegenerative diseases, demonstrating neuroprotective effects. However, their impact on brain iron content and neurological function following ICH has yet to be reported. Here, we explored the potential of tungsten-based polyoxometalate (W-POM) NCs as ferroptosis inhibitors targeting the iron metabolic pathway mediated by S100A8/A9 for the treatment of ICH. Results We successfully synthesized ultra-small reduced W-POM NCs that can rapidly cross the blood-brain barrier and are cleared through the kidney. In vitro experiments demonstrated that W-POM NCs exhibit significant and stable ROS scavenging activity while effectively alleviating iron overload and associated neuronal damage. In vivo, W-POM NCs treatment restored iron metabolism homeostasis, suppressed neuroinflammation and oxidative stress, ultimately alleviating severe neurological damage and motor deficits in ICH mice. Proteomic combined with bioinformatic analyses identified two core genes, S100A8 and S100A9, most associated with W-POM NCs intervention in ICH. Further experiments confirmed that W-POM NCs act by modulating the toll-like receptor 4/hepcidin/ferroportin signaling pathway, thereby regulating iron metabolism and reducing secondary brain injury. Conclusions This study pioneers the application of polyoxometalates in intracerebral haemorrhage, offering a novel and promising therapeutic approach for the management of ferroptosis-related brain injuries.
研究领域:
神经病学
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药理学
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纳米技术
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生物化学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2020
·
IF 4.099
Xi Zhao,Zhenhua Liu,Jie Gao,Hu Li,Xiaorong Wang,Yinchuan Li,Fei Sun
Busulfan is commonly used for cancer chemotherapy, nevertheless it cause male infertility via damaging the germ cells. Therefore, the underlying mechanism should be explored. In the present study, we demonstrated for the first time that ferroptosis was involved in busulfan-induced oligospermia in mice. Mice were given testicular injection of busulfan on both sides at the dose of 4 mg/kg body weight to establish the model of oligospermia. Four weeks later, the results showed that busulfan-treated mice exhibited decreased sperm concentration and motility, along with features of typical ferroptosis in testis, such as increased malondialdehyde (MDA) content and prostaglandin-endoperoxide synthase (PTGS2) mRNA expression, and decreased NADPH content. Inhibition of ferroptosis by ferrostatin-1 (Fer-1) or deferoxamine (DFO) partially alleviated busulfan-induced oligospermia in mice. Additionally, we also revealed that busulfan treatment induced spermatogenic cells ferroptosis by down-regulating nuclear factor-E2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4) expressions, and decreasing iron efflux through reduction of ferroportin 1 (FPN1) expression. Fer-1 or DFO obviously reversed busulfan-induced ferroptosis by increasing Nrf2, GPX4 and FPN1 expressions. Furthermore, after activation of Nrf2 by sulforaphane, sperm concentration and motility in busulfan-treated mice increased, accompanied by enhanced expressions of GPX4 and FPN1. These findings imply that busulfan-induced ferroptosis might be mediated via inhibition of Nrf2-GPX4 (FPN1) signaling pathway, and highlight that targeting ferroptosis serves as a potential strategy for prevention of busulfan-induced damage and male infertility.
研究领域:
药理学
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生殖生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
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