INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2024
·Vol. 25
·期 5
·2493
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IF 4.9
Zhu Ying,Meng Yin,Zifu Zhu,Zheng Shang,Yanqun Pei,Jing Liu,Qun Liu
Iron is an indispensable nutrient for the survival ofToxoplasma gondii; however, excessive amounts can lead to toxicity. The parasite must overcome the host’s “nutritional immunity” barrier and compete with the host for iron. SinceT. gondiican infect most nucleated cells, it encounters increased iron stress during parasitism. This study assessed the impact of iron stress, encompassing both iron depletion and iron accumulation, on the growth ofT. gondii. Iron accumulation disrupted the redox balance ofT. gondiiwhile enhancing the parasite’s ability to adhere in high-iron environments. Conversely, iron depletion promoted the differentiation of tachyzoites into bradyzoites. Proteomic analysis further revealed proteins affected by iron depletion and identified the involvement of phosphotyrosyl phosphatase activator proteins in bradyzoite formation.Keywords:Toxoplasma gondii;iron depletion;iron accumulation;bradyzoite differentiation
研究领域:
寄生虫学
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分子生物学
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PubMed
高影响因子
PHYTOMEDICINE
·
2019
·
IF 4.18
Dan Chen,Ya-Xian Wu,Yu-bao Qiu,Bin-bin Wan,Gang Liu,Jun-liang Chen,Mu-dan Lu,Qing-feng Pang
Background Hypoxia is commonly existed in tumors and lead to cancer cell chemo/radio-resistance. It is well-recognized that tumor hypoxia is a major challenge for the treatment of various solid tumors . Hyperoside (quercetin-3-O-galactoside, Hy) possesses antioxidant effects and has been reported to protect against hypoxia/reoxygenation induced injury in cardiomyocytes . Therefore, Hy may be attractive compound applicable to hypoxia-related diseases . Purpose This study was designed to determine the role of Hy in hypoxia-induced proliferation of non-small cell lung cancer cells and the underlying mechanism. Study Design and Methods A549, a human non-small cell lung cancer (NSCLC) cell line, was used in the present study. 1% O 2 was used to mimic the in vivo hypoxic condition of NSCLC. The potential mechanisms of Hy on hypoxia-induced A549 survival and proliferation, as well as the involvement of AMPK/HO-1 pathway were studied via CCK-8 assay, EdU staining, flow cytometry, qRT-PCR and western blot . Results We showed that pretreatment with Hy suppressed hypoxia-induced A549 survival and proliferation in dose-dependent manner. In terms of mechanism, hypoxia-treated A549 showed the lower AMPK phosphorylation and the reduced HO-1 expression, which were reversed by Hy pretreatment. Both AMPK inhibitor (Compound C) and HO-1 activity inhibitor (Zinc protoporphyrin IX) abolished Hy-evoked A549 cell death under hypoxia stimuli. Of note, Ferrous iron contributed to Hy-induced A549 cell death under hypoxia, while Hy had no effect on lipid peroxidation under hypoxia. Conclusion Taken together, our results highlighted the beneficial role of Hy against hypoxia-induced A549 survival and proliferation through ferrous accumulation via AMPK/HO-1 axis.
研究领域:
肿瘤学
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药理学
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分子生物学
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PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
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2024
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IF 3.7
Xiuhao Yu,Shaokun Chen,Hailin Wang
Chlorobenzoquinones (CBQs) are a class of emerging water disinfection byproducts that pose significant risks to public health. In this study, we found that three CBQs (tetrachloro-1,4-benzoquinone, 2,5-dichloro-1,4-benzoquinone, and 2-chloro-1,4-benzoquinone) can significantly aggravate cell death caused by Ras-selective lethal small molecule 3 (RSL3). Further study showed that the cell death caused by CBQs, either alone or in combination with RSL3, was related to iron accumulation and GPX4 inactivation, suggesting the occurrence of ferroptosis. Furthermore, reactive oxygen species are found to play a potential key role in mediating the toxicity of CBQs in CBQs and RSL3-induced ferroptosis. These findings will be helpful in understanding the toxic mechanism of CBQs to mammalian cells.
研究领域:
毒理学
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细胞生物学
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环境科学
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公共卫生
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PubMed
高影响因子
International Journal of Environmental Science and Technology
·
2022
·Vol. 20
·期 3
·2929-2938
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IF 3.519
Nguyen L. T. T.,Vo K. T. M.,Nguyen T. A.,Phan T. D.,Kwangsoo
In the present study, Acrostichum aureum Linn. (AAL) was proved as an accumulator of iron and a potential candidate to remove iron pollutants from groundwater. The iron-loaded biochar converted from the iron-contaminated AAL plants was determined the characterization and photocatalytic activity to demonstrate the potential for reusing the AAL biomass enriched with iron. In a 47-day hydroponic experiment, AAL plants could steadily grow in 20.0 mg L −1 Fe(NO 3 ) 3 solutions and pH ranging from 6.0 to 7.0. The total amount of iron introduced into the phytoremediation system is 240 mg iron, of which the AAL plants accumulate about 70%. X-ray diffraction (XRD) analysis showed that the iron-enriched biochar (named Fe-Bio-C) mainly consists of α -Fe 2 O 3 , and the Fe content determined by EDX is around 23 wt%. BET results revealed that the iron-enriched biochar possesses a higher specific surface area, around 266.9 m 2 g −1 , compared to the original biochar, around 18.2 m 2 g −1 . The photocatalytic performance of the Fe-Bio-C was studied in the discoloration of methyl orange (MO), with a maximum MO removal capacity of 18.8 mg g −1 . These findings show the phytoaccumulation of Acrostichum aureum Linn. plants to remove iron pollutants from groundwater and the potential application of the iron-accumulated biomass.
研究领域:
环境科学
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植物修复
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材料科学
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催化
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水处理
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DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Jixun Li,Ruzhen Feng,Wei Yang,Peiyao Liang,Tianming Qiu,Jingyuan Zhang,Xiance Sun,Qiujuan Li,Guang Yang,Xiaofeng Yao
Perfluorooctane sulfonate (PFOS) is known as a persistent organic pollutant. A significant correlation between PFOS and liver ferroptosis has been unveiled, but the precise mechanism needs to be elucidated. In prior research, we found that PFOS treatment provoked mitochondrial iron overload. In this study, we observed a gradual increase in lysosomal iron in L-O2 cells after exposure to PFOS for 0.5–24 h. In PFOS-exposed L-O2 cells, suppressing autophagy relieved the lysosomal iron overload. Inhibiting transient receptor potential mucolipin 1 (TRPML1), a calcium efflux channel on the lysosomal membrane, led to a further rise in lysosomal iron levels and decreased mitochondrial iron overload during PFOS treatment. Suppressing VDAC1, a subtype of voltage-dependent anion-selective channels (VDACs) on the outer mitochondrial membrane, had no impact on PFOS-triggered mitochondrial iron overload, whereas restraining VDAC2/3 relieved this condition. Although silencing VDAC2 relieved PFOS-induced mitochondrial iron overload, it had no effect on PFOS-triggered lysosomal iron overload. Silencing VDAC3 alleviated PFOS-mediated mitochondrial iron overload and led to an additional increase in lysosomal iron. Therefore, we regarded VDAC3 as the specific VDACs subtype that mediated the lysosomes-mitochondria iron transfer. Additionally, in the presence of PFOS, an enhanced association between TRPML1 and VDAC3 was found in mice liver tissue and L-O2 cells. Our research unveils a novel regulatory mechanism of autophagy on the iron homeostasis and the effect of TRPML1-VDAC3 interaction on lysosomes-mitochondria iron transfer, giving an explanation of PFOS-induced ferroptosis and shedding some light on the role of classic calcium channels in iron transmission.
研究领域:
毒理学
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细胞生物学
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环境科学
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Yuying He,Biyang Zhu,Huamai Qiu,Lijun You,Lianzhu Lin,Sandra Pedisić
Iron dextran complex is commonly used to treat iron deficiency anemia (IDA). In this work, dextran was degraded and oxidized by UV/H 2 O 2 treatment, and the product Dex-90 was chelated with FeCl 3 to prepare the iron dextran complex (Dex-90-Fe). Results showed that UV/H 2 O 2 treatment could significantly decrease the molecular weight of dextran and increase its carboxyl content, making it easier to chelate with iron (III). Moreover, Dex-90-Fe had a high iron content (30.77 % ± 0.87 %) and good thermal stability, which might be formed by Dex-90 with iron (III) via Fe O bond. Furthermore, the therapeutic effects of Dex-90-Fe on IDA were investigated in rats. After oral administration, Dex-90-Fe significantly improved hematological parameters, increased serum iron and serum ferritin, facilitated iron accumulation in the liver and spleen, and regulated the gene expressions of iron homeostasis. In summary, the iron dextran complex Dex-90-Fe prepared from UV/H 2 O 2 -degraded dextran could be developed as an iron supplement.
研究领域:
药剂学
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生物无机化学
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营养学
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血液学
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分子药理学
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药物代谢
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纳米医学
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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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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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PubMed
ADVANCED MATERIALS
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2025
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IF 26.8
Zekun Wang,Fangyuan Chen,Zhongkun Wang,Mengru Wu,Man Jiang,Zhekang Zheng,Yingying Li,Qing Li,Qingqing Wang,Dongdong Sun,Qingqing Miao
Nanozyme-driven ferroptosis provides a promising therapeutic strategy against drug-resistant bacterial infections by inducing iron overload and oxidative stress. However, bacterial metal transport proteins (MTP) and antioxidant systems can reduce iron accumulation and lipid peroxidation, limiting the efficacy of ferroptosis-based therapies and promoting resistance. Single-atom and chiral nanozymes, with their high atomic utilization and catalytic specificity, may provide an effective approach to overcoming bacterial defense mechanisms, which has been not exploited. In this study, we report D-chiral single-atom iron–carbon dot nanozymes (DFe-NSC) for effective bacterial infection treatment. Compared to L-chiral form (LFe-NSC), DFe-NSC exhibits significantly higher peroxidase (POD)-like and glutathione peroxidase (GPx)-like activities. The enhanced catalytic activity promotes reactive oxygen species (ROS) generation and glutathione depletion, disrupting bacterial redox homeostasis. More intriguingly, DFe-NSC more effectively modulates the expression and iron-regulatory function of MTP (including Fur and FtnA) than LFe-NSC. This will induce substantial accumulation of Fe 2 ⁺ intracellularly and thereafter lipid peroxidation, thereby facilitating the bactericidal effects of ferroptosis-like cell death. Resultantly, DFe-NSC exhibit markedly enhanced antibacterial and antibiofilm activities in diabetic infected wound and osteomyelitis models. This study introduces a chiral catalysis–MTP regulation strategy to induce bacterial ferroptosis-like death, providing a promising alternative for drug-resistant infection treatment.
研究领域:
纳米医学
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抗菌治疗
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催化
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传染病
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材料科学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Leyong Yuan,Yan Sun,Ning Zhou,Weipeng Wu,Weidong Zheng,Yukun Wang
Silicosis is a fatal occupational lung disease which currently has no effective treatment. Dihydroquercetin (DHQ) is a flavonoid compound known for its anti-inflammatory, anti-oxidant and anti-cancer bioactivity. However, whether DHQ protects against silica-induced lung fibrosis remains unknown. Therefore, we aimed to investigate the effect of DHQ on silica-induced lung fibrosis and the underlying molecular mechanism in vivo and in vitro . Our results demonstrated that DHQ treatment markedly attenuated SiO 2 -induced inflammation and fibrosis degree of lung tissues in the C57BL/6 mice. Additionally, experiments in vitro also confirmed that conditioned medium from DHQ-treated human bronchial epithelial (HBE) cells significantly decreased expression of fibrosis markers of human fetal lung fibroblast cells (MRC-5), such as α-SMA, collagen1 and fibronectin. Interestingly, HBE cells treated by DHQ showed few morphological features of ferroptosis compared with SiO 2 -treated cells. Furthermore, DHQ treatment remarkably inhibited ferroptosis in activated HBE cells by decreasing the accumulation of iron and lipid peroxidation products, and increasing levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4), whereas stimulation of ferroptosis by specific inducer erastin deeply impaired anti-fibrosis effect of DHQ in vitro . More importantly, our results showed that DHQ also evidently suppressed ferritinophagy by down-regulation of microtubule-associated protein 1A/1B-light chain 3 (LC3), and up-regulation of ferritin heavy chain 1 (FTH1), nuclear receptor co-activator 4 (NCOA4) in activated HBE cells. Nevertheless, activation of ferritinophagy by specific inducer rapamycin (Rapa) evidently blocked DHQ-inhibited HBE cells ferritinophagy and anti-fibrosis effect of DHQ. Overall, our research revealed that inhibition of ferritinophagy-mediated HBE cells ferroptosis was responsible for DHQ to ameliorate SiO 2 -induced lung fibrosis, which provided a preliminary theoretical basis for the clinical application of DHQ in the treatment of silicosis.
研究领域:
药理学
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毒理学
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肺病学
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细胞生物学
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分子生物学
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PubMed
高影响因子
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