Nature Communications
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2025
·Vol. 16
·期 1
·1-14
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IF 15.7
Tong Li,Wang Jie,Ma Yunjin,Wang Chunying,Fu Yue,Li Qi,Gao Chengjiang,Song Hui,Qin Ying,Zhao Chunyuan,Zhao Wei
Viruses rely on intracellular materials, including iron, to complete their life cycles and iron withholding may limit viral infections. However, the mechanisms through which viruses disrupt host iron homeostasis and the impact of intracellular iron on the host’s antiviral defense aren’t well studied. Here we show that viral infections facilitate the polyubiquitination and degradation of ferroportin (FPN1, the only cellular iron exporter) by upregulating the host E3 ubiquitin ligase DTX3L, leading to an elevation in cellular iron levels. Excessive ferrous iron suppresses type I IFN responses and autophagy by promoting TBK1 hydroxylation and STING carbonylation in macrophages. FPN1 deficiency suppresses host antiviral defense and facilitates viral replication in vitro and in vivo, while DTX3L deficiency has the opposite effect. These results reveal that viruses hijack host FPN1 to disrupt iron withholding and achieve immune escape, and suggest that iron homeostasis maintained by FPN1 is required for the optimal activation of TBK1- and STING-dependent antiviral responses.
研究领域:
微生物学
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免疫学
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Wenli Guo,Jinjin Zhang,Xiaoqian Zhang,Quanzhong Ren,Guangzhe Zheng,Jianxin Zhang,Guoxing Nie
Cadmium (Cd) pollution is considered a pressing challenge to eco-environment and public health worldwide. Although it has been well-documented that Cd exhibits various adverse effects on aquatic animals, it is still largely unknown whether and how Cd at environmentally relevant concentrations affects iron metabolism . Here, we studied the effects of environmental Cd exposure (5 and 50 μg/L) on iron homeostasis and possible mechanisms in common carp. The data revealed that Cd elevated serum iron, transferrin saturation and iron deposition in livers and spleens, leading to the disruption of systemic iron homeostasis. Mechanistic investigations substantiated that Cd drove hemolysis by compromising the osmotic fragility and inducing defective morphology of erythrocytes. Cd concurrently exacerbated hepatic inflammatory responses, resulting in the activation of IL6-Stat3 signaling and subsequent hepcidin transcription. Notably, Cd elicited ferroptosis through increased iron burden and oxidative stress in livers. Taken together, our findings provide evidence and mechanistic insight that environmental Cd exposure could undermine iron homeostasis via erythrotoxicity and hepatotoxicity. Further investigation and ecological risk assessment of Cd and other pollutants on metabolism-related effects is warranted, especially under the realistic exposure scenarios.
研究领域:
环境科学
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毒理学
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水生生物学
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分子生物学
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DOI
PubMed
高影响因子
CHEMOSPHERE
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2017
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IF 4.208
Ping Xiang,Rui-Wen He,Rong-Yan Liu,Kan Li,Peng Gao,Xin-Yi Cui,Hongbo Li,Yungen Liu,Lena Q. Ma
Cancerous human liver cell line has been used to test the hepatic toxicity of indoor dust, showing its organic extract decreases cell viability. However, little is known about its impact on normal human liver cell line. In the present study, we compared the cellular responses between carcinoma cell line (HepG2) and normal cell line (HL-7702) after exposing to 10–640 μg/100 μL organic dust extract for 24 h. The dust extract caused cytotoxicity, oxidative damage, inflammatory response and loss of mitochondrial transmembrane potential (MMP) in both cells. The inhibition of cell viability in HL-7702 cells was stronger than that in HepG2 cells, with HL-7702 cells having lower LC 50 . Higher production of oxidative stress , more loss of MMP and stronger suppression of antioxidant enzymes mRNA level occurred in HepG2 cells, while mRNA expression and hepcidin secretion were enhanced in HL-7702 cells at 40/100 μL, indicating the dust extract probably perturbed their liver Fe homeostasis . Our data showed considerable differences in cellular responses between normal and cancerous cell lines. To obtain accurate data, normal hepatocytes should be employed as they better match with the in vivo tissue than cancerous cell lines.
研究领域:
毒理学
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细胞生物学
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环境健康
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-23
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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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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Hao Wu,Xiping Yuan,Yong He,Jinwei Gao,Min Xie,Zhonggui Xie,Rui Song,Dongsheng Ou
Niclosamide (NIC) is a commonly used insecticide and molluscicide in the prevention and treatment of parasitic diseases in fish. The utilization of NIC has the potential to disrupt the microbial community present on the mucosal tissue of fish, leading to localized inflammatory responses. The objective of this study was to evaluate the impact of NIC on the immune system and bacterial populations within the gill and gut of Mylopharyngodon piceus . Fish were subjected to varying concentrations of NIC, including a control group (0 μg/L), a low NIC group (15% 96 h LC50, LNG, 9.8 μg/L), and a high NIC group (80% 96 h LC50, HNG, 52.5 μg/L). Gill and gut samples were collected 28 days post-exposure for analysis. The findings revealed that the 96-h LC 50 for NIC was determined to be 65.7 μg/L, and histopathological examination demonstrated that exposure to NIC resulted in gill filament subepithelial edema, exfoliation, degeneration, and a decrease in gill filament length. Furthermore, the gut exhibited apical enterocyte degeneration and leucocyte infiltration following NIC exposure. Additionally, NIC exposure led to a significant elevation in the levels of immunoglobulin M (IgM), complement component 3 (C3), and complement component 4 (C4) in both gill and gut tissues. Moreover, the activity of lysozyme (LYZ) was enhanced in the gill, while the activities of peroxidase (POD) and immunoglobulin T (IgT) were increased in gut tissue. The exposure to NIC resulted in enhanced mRNA expression of c3 , c9 , tnfα , il6 , il8 , and il11 in the gill tissue, while decreasing c3 and il8 expression in the gut tissue. Furthermore, the natural resistance-associated macrophage protein ( nramp ) mRNA increased, and liver-expressed antimicrobial peptide 2 ( leap2 ) mRNA decreased in gill and gut tissues. And hepcidin ( hepc ) mRNA levels rose in gill but fell in gut tissue. NIC exposure also led to a decrease in gill bacterial richness and diversity, which significantly differed from the control group, although this separation was not significant in the gut tissue. In conclusion, the administration of NIC resulted in alterations in both the immune response and mucosal microbiota of fish. Furthermore, it was noted that gills displayed a heightened vulnerability to sublethal effects of NIC in comparison to gut tissues.
研究领域:
水生毒理学
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免疫学
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微生物学
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鱼类生物学
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DOI
PubMed
高影响因子
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