Advanced Healthcare Materials
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2025
·
IF 9.6
Weibo Zhang,Chong Chen,Ran Wang,Yixuan Li,Yinhua Zhu,Jiazeng Sun,Yongting Luo,Junjie Luo,Liang Zhao,Yanan Sun,Huiyuan Guo,Hao Zhang,Bing Fang,Yao Hu,Rong Liu,Xiaoyu Wang,Jiayue Guo,Ping Liu,Peng An,Pengjie Wang,Juan Chen,Fazheng Ren
Human serum albumin (HSA) plays an indispensable role as a carrier of endogenous and exogenous substances in vivo. The efficiency of endocytosis determines the transport capacity. However, the potential for enhancing the efficiency of HSA endocytosis remains largely unknown. This research represented a substantial advancement, revealing that Fe 2+ markedly increased HSA endocytosis. Moreover, Fe 2+ facilitated the endocytosis and transport of HSA in vivo. The enhancement in HSA uptake facilitated by Fe 2+ is markedly decreased following iron chelation, indicating a specific interaction between Fe 2 ⁺ and HSA that promoted endocytosis. Moreover, the study elucidated that FcRn and caveolin regulated HSA endocytosis under normal conditions. Yet, in the presence of Fe 2 ⁺, endocytosis shifted toward clathrin- and caveolin-enriched membrane domains, requiring both divalent metal transporter 1 (DMT1) and FcRn for efficient process completion. Thereby a new pathway is discovered for Fe 2+ -dependent HSA endocytosis involving DMT1 and clathrin. This findings highlighted the crucial role of iron in enhancing HSA endocytosis and transport, establishing Fe 2+ as a vital endocytic enhancer that required binding to HSA to substantially improve its uptake. This insight into the mechanism of HSA endocytosis not only expands the understanding of protein transport but also opens new avenues for therapeutic intervention.
研究领域:
生物化学
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细胞生物学
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医学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Nan Li,Ruiyan Wang,Zeyuan Deng,Jianqun Zhou,Wenwen Li,Qian Du,Liufeng Zheng
Sucrose emerges as a metal-ion chelating agent with excellent stability that may increase metal-ion absorption. This study aimed to characterize the structure of zinc–sucrose complex and investigate its ability to promote zinc absorption in Caco-2 monolayer cells and mice. Based on the results of the inductively coupled plasma emission spectrometer (ICP-ES), scanning electron microscopy–energy-dispersive X-ray spectroscopy (SEM-EDX), and Fourier transform infrared spectroscopy (FT-IR), it can be inferred that zinc and sucrose were chelated at a 1:1 ratio, with the hydroxyl groups playing a significant role. The Caco-2 monolayer cell model revealed that zinc–sucrose complex increased the amount of zinc uptake, retention, and transport in a dose- and time-dependent manner. Through the upregulation of genes and proteins for ZIP4, MT1, and DMT1, treatment with zinc–sucrose complex improved the proportion of absorbed zinc utilized for transport compared to ZnCl2 (26.21 ± 4.96 versus 8.50 ± 1.51%). Pharmacokinetic analysis of mice confirmed the zinc absorption-promoting effect of zinc–sucrose complex, as indicated by the considerably higher serum zinc level (4.16 ± 0.53 versus 2.56 ± 0.45 mg/L) and intestinal ZIP4, MT1, and DMT1 gene expression than ZnCl2. Further treatment of different zinc channel inhibitors and CETSA demonstrated the direct interaction of zinc–sucrose complex with ZIP4 protein and ZIP4-mediated cellular transport of zinc–sucrose complex. These findings provide a novel insight into the zinc absorption-promoting mechanism of zinc–sucrose complex, which could be used as an ingredient in functional foods to treat zinc deficiency.
研究领域:
营养学
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药理学
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分子生物学
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细胞生物学
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生物化学
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DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-15
·
IF 14.7
Jiang Jun,Yang Lili,Xie Qianqian,Liu Xi,Jiang Jie,Zhang Jie,Zhang Shuping,Zheng Huizhen,Li Wenjie,Cai Xiaoming,Liu Sijin,Li Ruibin
Ferroptosis is a promising strategy for cancer therapy, with numerous inhibitors of its braking axes under investigation as potential drugs. However, few studies have explored the potential of activating the driving axes to induce ferroptosis. Herein, phosphatidylcholine peroxide decorating liposomes (LIP PCPO ) are synthesized to induce ferroptosis by targeting divalent metal transporter 1 (DMT1). LIP PCPO is found to boost lysosomal Fe 2+ efflux by inducing cysteinylation of lysosomal DMT1, resulting in glutathione peroxidase 4 (GPX4) suppression, glutathione depletion and ferroptosis in breast cancer cells and xenografts. Importantly, LIP PCPO induced ferroptotic cell death is independent of acquired resistance to radiation, chemotherapy, or targeted agents in 11 cancer cell lines. Furthermore, a strong synergistic ferroptosis effect is observed between LIP PCPO and an FDA-approved drug, artesunate, as well as X rays. The formula of LIP PCPO encapsulating artesunate significantly inhibits tumor growth and metastasis and improves the survival rate of breast cancer-bearing female mice. These findings provide a distinct strategy for inducing ferroptosis and highlight the potential of LIP PCPO as a vector to synergize the therapeutic effects of conventional ferroptosis inducers.
研究领域:
癌症生物学
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药理学
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治疗学
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分子生物学
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DOI
PubMed
高影响因子
Chinese Herbal Medicines
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2020
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IF 0
Xin Li,Xiao-wen Jiang,Hai-xiao Chu,Qing-chun Zhao,Huai-wei Ding,Chao-hong Cai
Objective Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra (SN). Our previous study demonstrated kukoamine A (KuA) to exhibit strong neuroprotective effects through antioxidative stress, and autophagy in MPTP/MPP + -induced PD models in vivo and in vitro . It is necessary to evaluate the efficacy of the anti-PD effects under various models. Methods In the present study, total chemical synthesis was used to obtain KuA, which performed low content in Lycii Cortex . Then, 6-OHDA-induced PD model of PC12 cells was used to investigate the effects of KuA on PD. Results Our results demonstrated that KuA ameliorated cell loss and mitochondrial membrane potential (MMP) loss, and inhibited Bax/Bcl-2 ratio increase that were induced by 6-OHDA. Iron accumulation in SN is thought to participate in neuronal death in PD, which subsequently resulted in oxidative stress and overexpression of α-synuclein caused by iron metabolism protein disorder. In our study, KuA could chelate cellular iron content and decrease iron influx. Moreover, KuA could upregulate the expression of ferroportin1 and Hephaestin, downregulate the expression of DMT1, TfR, and Ferritin to maintain cellular iron homeostasis avoiding neuronal death from cellular iron deposition. Moreover, KuA could decrease the expression of a-synuclein in cells. All the results indicated that KuA protected against neurotoxin-induced PD due to the apoptosis inhibition and iron homeostasis maintaining. Conclusion KuA treatment might represent a neuroprotective treatment for PD.
研究领域:
神经科学
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药理学
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细胞生物学
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神经退行性疾病
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DOI
PubMed
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
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神经科学
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产品关联
DOI
PubMed
高影响因子
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