Communications Biology
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2024
·Vol. 7
·期 1
·1-13
·
IF 5.2
Lin Hui,Lin Shuaijun,Shi Liuhong,Xu Guangsen,Lin Manjie,Li Supeng,Chen Jiale,Li Zhiquan,Nakazibwe Catherine,Xiao Yunbei,Li Xiaokun,Pan Xuebo,Wang Cong
The acquisition of ectopic fibroblast growth factor receptor 1 (FGFR1) expression is well documented in prostate cancer (PCa) progression, notably in conferring tumor growth advantage and facilitating metastasis. However, how FGFR1 contributes to PCa progression is not fully revealed. Here we report that ectopic FGFR1 in PCa cells promotes transferrin receptor 1 (TFR1) expression and expands the labile iron pool (LIP), and vice versa. We further demonstrate that FGFR1 stabilizes iron regulatory proteins 2 (IRP2) and therefore, upregulates TFR1 via promoting IRP2 binding to the IRE of TFR1. Deletion of FGFR1 in DU145 cells decreases the LIP, which potentiates the anticancer efficacy of iron chelator. Intriguingly, forced expression of IRP2 in FGFR1 depleted cells reinstates TFR1 expression and LIP, subsequently restoring the tumorigenicity of the cells. Together, our results here unravel a new mechanism by which FGFR1 drives PCa progression and suggest a potential novel target for PCa therapy.
研究领域:
肿瘤学
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细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Catalysis
·
2024
·
IF 11.3
Xiaoli Sun,Jie Liu,Yunmei Du,Yanru Liu,Wenna Wang,Dehong Chen,Ruiyong Zhang,Lei Wang
Constructing multifunctional electrodes with high metal utilization by a one-step synthesis strategy is a serious challenge. Herein, Zn-IrP2/FeP with dual-functional activity induced by trimetallic sites are constructed by the “one-step phosphorization”. Relevant characterizations and DFT calculations reveal that Ir and Fe act as the HER and HzOR sites, respectively, promoting the overall hydrazine splitting (OHzS) at the industrial-level current. Specially the Zn dopant, as an auxiliary active site for Ir–Fe dual-active sites, optimizes the physical structure, electronic configuration, d-band center, and adsorption intermediate capabilities of the Zn-IrP2/FeP/IF electrode from multiple perspectives. As expected, Zn-IrP2/FeP/IF only requires 223.0 and 382.0 mV to drive the industrial-grade current density of 1 A cm–2 for HER and HzOR, respectively. Notably, the voltage of the OHzS for Zn-IrP2/FeP/IF to reach 500 mA cm–2 is 1.38 V lower than that of the OWS. In summary, trimetallic sites exhibit synergetic electrocatalytic functions and synergistically maximize electrocatalytic efficiency. Moreover, the multiactive site mechanism of the dopant as an auxiliary active site is innovatively proposed in this work. This presents a valuable idea for designing multimetal catalysts with high metal utilization efficiency and in-depth investigation of catalytic mechanisms.
研究领域:
电化学
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材料科学
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催化
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能源转换
✓ 已验证
DOI
高影响因子
APPLIED SURFACE SCIENCE
·
2021
·
IF 6.707
Yingnan Yang,Pang Yang,Linsen Zhou,Ruilin He,Yawei Hao,Jingchuan Wang,Ruizhi Qiu,Xiaochong Zhao,Lijun Yang
Platinum-group metals are the most promising catalysts choice for hydrogen evolution reaction (HER) due to their good catalytic stability and optimum Gibbs free energy for hydrogen adsorption and desorption. However, high cost restricts their industrial application. To lower price, the most commonly used method is to reduce noble metals’ dosage. Herein, iridium (Ir) and its diphosphide (IrP 2 ) based on one-dimensional carbon nanofibers (CNFs) are easily fabricated by electrospinning and following calcination, and then are applied as efficient catalysts for HER. Both Ir-CNFs and IrP 2 -CNFs show excellent HER performances with overpotentials of 22 mV and 19 mV under the current density of 10 mA cm −2 in alkaline medium, respectively. The experimental results are further proved by density function theory (DFT) calculations, in which IrP 2 (2 0 0) shows better HER kinetics than Ir (1 1 1) with lower water adsorption and hydrogen evolution energies. This work presents a simple method to prepare Ir-CNFs and IrP 2 -CNFs and provides a new feasibility for design and synthesis of efficient and stable HER catalysts.
研究领域:
材料科学
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催化化学
·
能源科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Qiang-Ming Li,Tong Xu,Xue-Qiang Zha,Xiao-Wen Feng,Feng-Yun Zhang,Jian-Ping Luo
Ethnopharmacological relevance Parkinson's disease (PD) is the second neurodegenerative disease that lacks effective treatments. Buddlejasaponin IVb (BJP-IVb) is the main bioactive component of herbs in genus Clinopodium which display antioxidative, anti-inflammatory and neuroprotective activities. However, the role of BJP-IVb in PD still remains unknown. Aim of the study This study aimed to evaluate the effect of BJP-IVb on dopaminergic neurodegeneration in PD and clarified the underlying mechanisms from the aspect of iron overload-mediated ferroptosis . Materials and methods One-methyl-4-phenylpyridinium (MPP + ) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD models were established in this study. Behavioral tests, cell cytotoxicity assay , tyrosine hydroxylase (TH) and Nissl staining were performed to evaluate the antiparkinsonian effect of BJP-IVb. Cellular ultrastructure, iron content and lipid peroxidation were detected to evaluate iron overload-mediated dopaminergic neuron ferroptosis. Iron regulatory protein 2 (IRP2) and iron transport-related proteins were detected by immunofluorescence and Western blot to evaluated iron transport. Finally, plasmid vector-mediated IRP2 overexpression were performed to further clarify the molecular mechanism. Results BJP-IVb alleviated MPP + -induced neurotoxicity in vitro and improved MPTP-induced dopaminergic neuron loss and motor dysfunctions of PD mice, confirming an effect of BJP-IVb against dopaminergic neurodegeneration of PD. Further results revealed that BJP-IVb protected against PD by suppressing iron overload-mediated dopaminergic neuron ferroptosis, as evidenced by the attenuated lipid peroxidation, decreased iron content and changes in cellular ultrastructure. Finally, the decreased iron regulatory protein (IRP2) was confirmed to be responsible for BJP-IVb-mediated ferroptosis suppression by modulating iron transport-related proteins and alleviating iron overload. Conclusion BJP-IVb suppressed iron overload-mediated dopaminergic neuron ferroptosis and improved motor dysfunctions in PD, which was achieved by inhibiting IRP2-mediated iron overload. This study provided a potential drug candidate for the treatment of PD.
研究领域:
神经科学
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药理学
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民族药理学
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神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2018
·Vol. 8
·期 1
·1-11
·
IF 4.122
Li Huihui,Zhao Hongting,Hao Shuangying,Shang Longcheng,Wu Jing,Song Chuanhui,Meyron-Holtz Esther G.,Qiao Tong,Li Kuanyu
Iron is essential for growth and proliferation of mammalian cells. The maintenance of cellular iron homeostasis is regulated by iron regulatory proteins (IRPs) through binding to the cognate iron-responsive elements in target mRNAs and thereby regulating the expression of target genes. Irp1 or Irp2 -null mutation is known to reduce the cellular iron level by decreasing transferrin receptor 1 and increasing ferritin. Here, we report that Irp1 or Irp2 -null mutation also causes downregulation of frataxin and IscU, two of the core components in the iron-sulfur cluster biogenesis machinery. Interestingly, while the activities of some of iron-sulfur cluster-containing enzymes including mitochondrial aconitase and cytosolic xanthine oxidase were not affected by the mutations, the activities of respiratory chain complexes were drastically diminished resulting in mitochondrial dysfunction. Overexpression of human ISCU and frataxin in Irp1 or Irp2 -null cells was able to rescue the defects in iron-sulfur cluster biogenesis and mitochondrial quality. Our results strongly suggest that iron regulatory proteins regulate the part of iron sulfur cluster biogenesis tailored specifically for mitochondrial electron transport chain complexes.
研究领域:
分子生物学
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细胞生物学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2019
·Vol. 197
·期 2
·580-590
·
IF 2.431
Zhang Jian,Huang Wanyue,Xu Feibo,Cao Zheng,Jia Fubo,Li Yanfei
Aluminum (Al) alters iron regulatory factors content and leads to the changes in iron-related proteins causing iron accumulation. But limited evidence ascertains this hypothesis. Therefore, our experiment was conducted and four groups of male Wistar rats were orally administrated of 0, 50, 150, and 450 mg/kg BW/d aluminum chloride (AlCl 3 ) for 90 days by drinking water, respectively. The cognitive function, pathological lesion of hippocampus, oxidative stress, as well as iron-related proteins and iron regulatory factors expression were detected. The results showed that AlCl 3 remarkably induced the oxidative stress and pathological lesion in the hippocampus and impaired the learning-memory ability. The contents of Al and iron increased in all AlCl 3 -exposed groups. Meanwhile, the increased divalent metal transporter 1 (DMT1) expression enhanced iron import and the decreased ferroportin 1 (Fpn1) expression reduced iron export in AlCl 3 -exposed groups. The iron accumulated and ferritin heavy chains (Fth) expression decreased in all AlCl 3 -exposed groups led to an increase in free iron. The study also showed that iron regulatory factor iron regulatory protein 2 (IRP2) was decreased and hepcidin was increased in AlCl 3 -exposed groups. The results indicated that AlCl 3 induces iron dyshomeostasis presenting as iron accumulation, the disordered expression of iron import, export, store, and regulatory proteins in rat hippocampus accompanied with oxidative stress, pathological lesion, and impaired learning-memory ability.
研究领域:
神经毒理学
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药理学
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分子生物学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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