LIPIDS
·
2016
·Vol. 52
·期 1
·27-35
·
IF 1.892
Pan Yao,Liu Benxin,Deng Zeyuan,Fan Yawei,Li Jing,Li Hongyan
The effects of two fatty acids, oleic acid (OLA) and elaidic acid (ELA) on normal human umbilical vein endothelial cells (HUVEC) and non-rafts HUVEC were investigated in this study. The expression levels of inflammatory cytokines (ICAM-1, VCAM-1 and IL-6) were analyzed. Western blot was used to analyze the expression levels of inflammation-related proteins (NF-κB, ERK1/2) and toll-like receptors 4 (TLR4). The results showed that the levels of nuclear translocation of NF-κB p65 and phosphorylated ERK1/2 were significantly decreased only in non-lipid rafts cells pretreated with trans fatty acid (TFA). The expression of TLR4 in the ELA-treated normal cells was higher than that in non-lipid rafts HUVEC. When the lipid rafts was destroyed by methyl-β-cyclodextrin, the levels of nuclear translocation of NF-κB p65, phosphorylated ERK1/2 and TLR4 were decreased significantly. Therefore, lipid rafts may be involved in TFA induced-inflammation in HUVEC through blocking the inflammatory signal pathway. Lipid rafts might be a platform for specific receptors such as TLR4 for TFA to activate the pro-inflammation on cell membranes.
研究领域:
细胞生物学
·
分子生物学
·
心血管研究
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2014
·
IF 3.107
Huan Rao,Li-Xin Ma,Ting-Ting Xu,Jing Li,Ze-Yuan Deng,Ya-Wei Fan,Hong-Yan Li
Our previous study showed that trans-fatty acids can cause apoptosis of endothelial cells through the caspase pathway and the mitochondrial pathway. The objective of this study was to explore how trans-fatty acids activate the caspase pathway, whether there exist specific receptors induced apoptosis by comparing normal cells and non-rafts cells treated with elaidic acid (9t18:1) and oleic acid (9c18:1), respectively. Compared to normal cells treated with 9t18:1, the cell viability increased by 13% and the number of apoptotic cells decreased by 3% in non-rafts cells treated with 9t18:1 (p < 0.05), and the expression levels of pro-apoptotic proteins such as caspase-3, -8, -9, Bax, and Bid decreased, and expression of antiapoptotic protein Bcl-2 increased (p < 0.05). In addition, Fas/FasL expression in cell membrane decreased significantly (p < 0.05). In conclusion, the lipid rafts and Fas/FasL pathway may involve in 9t18:1-induced apoptosis of human umbilical vein endothelial cells.
研究领域:
细胞生物学
·
分子生物学
·
心血管研究
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DOI
PubMed
高影响因子
TOXICOLOGICAL SCIENCES
·
2016
·Vol. 153
·期 2
·303-315
·
IF 3.88
Fu Juanli,Shi Qiong,Song Xiufang,Liu Zixuan,Wang Yawen,Wang Yuxin,Song Erqun,Song Yang
Tetrachlorobenzoquinone (TCBQ) is a confirmed active metabolite of a well-known environmental pollutant pentachlorophenol (PCP). Unfortunately, there is insufficient knowledge present available on TCBQ’s toxicity. Our previous studies indicated that TCBQ induces inflammatory response in vivo and in vitro; however, its exact mechanism needs further investigation. Toll-like receptors (TLRs) play a crucial role in conveying of inflammatory signaling, whilst high-mobility group box 1 (HMGB1) functions as a transcription-enhancing nuclear protein that regulates inflammation. Indeed, this study demonstrated that TCBQ induces the secretion/translocation of HMGB1, which in turn activates its receptors, TLR family gene (especially TLR4) and receptor for advanced glycation end-products (RAGE) expressions. Consistently, the binding affinity of HMGB1 with its receptors also increased. In the case of HMGB1 or TLR4 deficiency, there were decreases in TCBQ-induced neuroinflammatory cytokine production and neuropathological changes, eg, neuronal loss, astrocyte and macrophage cells activation. Moreover, we found the mobilization of TLR4 into lipid rafts occurs in response to TCBQ exposure, lipid rafts disruptors weakened this effect, suggested lipid rafts play an essential role for TLR4-mediated signal transduction and target inflammatory cytokines expressions. In summary, our current findings revealed a previously unknown mechanism of TCBQ-induced neurological inflammation related to HMGB1-TLR4 signaling.
研究领域:
毒理学
·
神经科学
·
免疫学
·
环境健康
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DOI
PubMed
高影响因子
Science Advances
·
2023
·Vol. 9
·期 23
·
IF 13.6
Zheng Dong,Juan Ma,Jiahuang Qiu,Quanzhong Ren,Qing’e Shan,Xuefeng Duan,Guangle Li,Yi Y. Zuo,Yu Qi,Yajun Liu,Guoliang Liu,Iseult Lynch,Min Fang,Sijin Liu
Mounting data suggest that environmental pollution due to airborne fine particles (AFPs) increases the occurrence and severity of respiratory virus infection in humans. However, it is unclear whether and how interactions with AFPs alter viral infection and distribution. We report synergetic effects between various AFPs and the H1N1 virus, regulated by physicochemical properties of the AFPs. Unlike infection caused by virus alone, AFPs facilitated the internalization of virus through a receptor-independent pathway. Moreover, AFPs promoted the budding and dispersal of progeny virions, likely mediated by lipid rafts in the host plasma membrane. Infected animal models demonstrated that AFPs favored penetration of the H1N1 virus into the distal lung, and its translocation into extrapulmonary organs including the liver, spleen, and kidney, thus causing severe local and systemic disorders. Our findings revealed a key role of AFPs in driving viral infection throughout the respiratory tract and beyond. These insights entail stronger air quality management and air pollution reduction policies.
研究领域:
环境科学
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病毒学
·
公共卫生
·
呼吸医学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Keying Liang,Shengsheng Mei,Xiangzheng Gao,Shanshan Peng,Jinbiao Zhan
Purpose T-DM1 is an antibody–drug conjugate (ADC) consisting of trastuzumab and DM1 linked together. T-DM1 binds to human epidermal growth factor receptor-2 (HER2) in tumors and then triggers the endocytosis of T-DM1 and release of payload. Therefore, endocytosis efficacy is considered as a critical step for the initiation of T-DM1 therapy; however, the endocytosis mechanism of T-DM1 remains poorly understood. Meanwhile, HER2 is regarded as an internalization-resistant receptor, which hinders the endocytosis and effectiveness of T-DM1. The present study is to explore the T-DM1 endocytosis pathway, which may provide insights into the internalization mechanism of ADCs and help to improve efficacy.Methods Confocal microscopy and flow cytometry were used to analyse T-DM1 intracellular trafficking and endocytosis efficiency, while Western blot assay was performed to detect T-DM1 degradation.Results We found that intracellular T-DM1 was increased to 50% within 12 h. T-DM1 was colocalized with cholera toxin B (CTxB), a lipid raft marker, within 2 h and then degraded in lysosome. Upon overexpression of caveolin-1 (CAV-1) and utilization of caveolae/lipid-raft disruptors, we found that temporal CAV-1 upregulation significantly facilitated T-DM1 endocytosis and degradation, whereas nystatin and lovastatin disrupted caveolae/lipid-raft structure and inhibited T-DM1 degradation. We demonstrate that T-DM1 internalizes through the lipid raft-mediated endocytosis in a CAV-1 dependent manner, rather than through the clathrin-mediated endocytosis in HER2-positive cancer cells.Conclusion Our findings suggest that modulation of the caveolae/lipid-raft mediated endocytosis may be a possible option for improving the clinical therapeutic effect of T-DM1 because it plays a key role in regulating T-DM1 internalization.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
·
分子生物学
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DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2021
·
IF 2.73
Shengyu Sun,Yourui Zou,Shaocai Hao,Zhanfeng Niu,Liang Wu
Objective Polydatin has been used in the treatment of various inflammatory diseases. However, its role in the regulation of neuroinflammation has not been reported. In this study, we designed to investigate the anti-inflammatory effects of polydatin in LPS-stimulated BV2 microglia cells.Methods Inflammatory mediators TNF-α, IL-1β, NO, and PGE2 production were measured by ELISA. The protein of signaling pathways were detected by western blot analysis.Results The results showed that polydatin significantly ameliorated the production of TNF-α, IL-1β, NO, and PGE2 up-regulated by LPS. Polydatin also blocked LPS-induced NF-κB activation. In addition, PI3K and AKT, the up-stream molecules of NF-κB signaling pathway, were inhibited by the treatment of polydatin. Also, we found the formation of lipid rafts was inhibited by polydatin through attenuating the cholesterol content. Finally, polydatin was found to increase the expression of ABCA1 and ABCG1.Conclusion In conclusion, the results of the present study suggested that polydatin exhibited its anti-inflammatory effects in BV2 cells through disrupting lipid rafts, which subsequently inhibiting PI3K/AKT signaling pathway.
研究领域:
药理学
·
神经科学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biosafety and Health
·
2020
·
IF 0
Cong Jin,Bin Che,Zhengyuan Guo,Chuan Li,Yang Liu,Wei Wu,Shiwen Wang,Dexin Li,Zongqiang Cui,Mifang Liang
Ebola virus (EBOV) is one of the most pathogenic viruses in humans which can cause a lethal hemorrhagic fever. Understanding the cellular entry mechanisms of EBOV can promote the development of new therapeutic strategies to control virus replication and spread. It has been known that EBOV virions bind to factors expressed at the host cell surface. Subsequently, the virions are internalized by a macropinocytosis-like process, followed by being trafficked through early and late endosomes. Recent researches indicate that the entry of EBOV into cells requires integrated and functional lipid rafts. Whilst lipid rafts have been hypothesized to play a role in virus entry, there is a current lack of supporting data. One major technical hurdle is the lack of effective approaches for observing viral entry. To provide evidence on the involvement of lipid rafts in the entry process of EBOV, we generated the fluorescently labeled Ebola virus like particles (VLPs), and utilized single-particle tracking (SPT) to visualize the entry of fluorescent Ebola VLPs in live cells and the interaction of Ebola VLPs with lipid rafts. In this study, we demonstrate the compartmentalization of Ebola VLPs in lipid rafts during entry process, and inform the essential function of lipid rafts for the entry of Ebola virus. As such, our study provides evidence to show that the raft integrity is critical for Ebola virus pathogenesis and that lipid rafts can serve as potential targets for the development of novel therapeutic strategies.
研究领域:
病毒学
·
细胞生物学
·
分子生物学
·
感染性疾病
·
生物医学成像
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DOI
Veterinary Sciences
·
2025
·Vol. 12
·期 3
·233
·
IF 2.3
Yang Yang,Xin Zhang,Jin Yang,Ziyan Wu,Junpeng Li,Ruilong Song,Chuang Meng,Guoqiang Zhu
Simple SummaryQuorum sensing (QS) not only regulates bacterial virulence through signaling molecules, but is also capable of causing direct damage to host cells. Previous studies have found a high correlation between N-acyl homoserine lactone (AHL) of the QS in the piglet intestine and piglet health. In a mouse model, AHL signaling N-(3-oxododecanoyl)-homoserine lactone (OdDHL) induced apoptosis of intestinal cells and damage to intestinal barrier. In a porcine intestinal epithelial cell model, OdDHL also was confirmed to induce apoptosis. The direct role and mechanism of OdDHL in the digestive tract of porcine animal models have not been elucidated. For the first time in a piglet model, we have verified that AHL induces apoptosis and disrupts the intestinal barrier, and we have also verified the protective effect of QS inhibitors. The present study also investigates the central role of cellular lipid rafts in the critical phase in which OdDHL adheres to cells and exerts functions. In cells where lipid rafts were eliminated, the ability of OdDHL adherence to cell surface was significantly reduced, and apoptosis induction was similarly impaired. This result indicates an important role for lipid rafts in relevant processes. This study provides basic data for the antimicrobial application of QSI in pig farming.Quorum sensing (QS) is a process by which bacteria sense their population density and regulate behavior accordingly. QS not only regulates bacterial virulence but also directly influences host cells. Previous studies have shown that QS is strongly associated with piglet intestinal health, but the mechanism is not yet clear. For the first time, we have confirmed in a piglet animal model that OdDHL directly damages intestinal cells in weaned piglets, disrupting the intestinal barrier. We also provide a preliminary exploration of the underlying mechanism of these effects. TUNEL assays confirmed that damage to the piglet intestinal barrier coincided temporally and spatially with dysregulated apoptosis. Lipid rafts, key components of the cell membrane, are involved in many biological processes, including the activation of apoptosis-related proteins. Following the disruption of the lipid raft structure in IPEC-J2 cells, the apoptosis rate under OdDHL stimulation decreased by 50%. These data demonstrate that lipid rafts mediate the attachment of OdDHL to porcine intestinal cells; then, OdDHL induces apoptosis in porcine intestinal cells through the mitochondrial and death receptor pathways, thereby compromising the integrity of the porcine intestinal barrier. This study provides foundational insights into the role of QS in piglet intestinal diseases.
研究领域:
动物科学
·
微生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Yi Wang,Mengyuan Guo,Peipei Wu,Chong Chen,Weibo Zhang,Fazheng Ren,Pengjie Wang,Shouyun Wu,Jianhuan Wei,Jie Luo,Jinghua Yu
This study provides insights into the composition and in-situ structures of the milk fat globule membrane (MFGM) in buffalo milk with different fat globule sizes (0.55 μm and 8.04 μm). Small fat globules contained a higher amount of MFGM proteins and polar lipids, while the content of MFGM components (except for ADPH) was greater per unit membrane area in large fat globules. A total of 386 differentially expressed proteins were identified, with many of the most differentially expressed proteins being associated with human diseases, such as cancer and elderly diseases. The coverage of sphingomyelin and certain MFGM proteins (BTN and PAS 6/7) on large fat globules was higher, potentially linked to the presence of larger, irregular lipid rafts and patch-shaped glycocalyxes, respectively. These findings suggest that small fat globules are suitable for nutritional fortification of buffalo milk, while large fat globules are appropriate for the preparation of functional dairy-based ingredients.
研究领域:
食品科学
·
营养学
·
生物化学
·
蛋白质组学
·
脂质组学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Dongyan Shao,Ting Bai,Bobo Zhu,Xiaojia Guo,Kai Dong,Junling Shi,Qingsheng Huang,Jie Kong
Natural killer (NK) cells have emerged as an important contributor to cancer immunotherapy, but their antitumor efficacy remains suboptimal. While cytokine-based priming shows promise in enhancing NK-cell activity, its clinical translation faces many challenges, including co-activation of multiple cytokines, poor pharmacokinetics, and limited mechanistic understanding. Here, we developed a polymeric micelle-based IL-15/IL-2 codelivery system (IL-15/2-PEG-PTMC) for NK-cell activation. In vivo studies demonstrated that the half-life of IL-15 and IL-2 as well as the recruitment of NK cell within tumor tissue was significantly increased after PEG-PTMC loading. Coupled with the coactivation effect of IL-15 and IL-2 conferred by this polymeric micelle-based system, it noticeably delayed the growth of tumors in mice compared to conventional NK cell activation approach, that was free IL-15 and IL-2. We also surprisingly found that cholesterol metabolism was highly involved in the NK cell activation by IL-15/2-PEG-PTMC. Following stimulation with IL-15/2-PEG-PTMC or IL-15, NK cells underwent a series of cholesterol metabolism reprogramming, which elevated the cholesterol levels on the NK cell membrane. This in turn promoted the formation of lipid rafts and actived immune synapse, effectively contributing to the enhancement of the NK cell's anti-tumor activity. We believe this will open a new avenue for improving the efficacy of NK cell immunotherapy by regulating cholesterol metabolism. This article is protected by copyright. All rights reserved
研究领域:
癌症生物学
·
免疫学
·
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2015
·
IF 5.736
Xiaomin Xia,Juanli Fu,Xiufang Song,Qiong Shi,Chuanyang Su,Erqun Song,Yang Song
Fulminant hepatic failure (FHF) is a lethal clinical syndrome characterized by the activation of macrophages and the increased production of inflammatory mediators . The purpose of this study was to investigate the effects of neohesperidin dihydrochalcone (NHDC), a widely-used low caloric artificial sweetener against FHF. An FHF experimental model was established in mice by intraperitoneal injection of D-galactosamine ( d -GalN) (400 mg/kg)/lipopolysaccharides (LPS) (10 μg/kg). Mice were orally administered NHDC for 6 continuous days and at 1 h before d -GalN/LPS administration. RAW264.7 macrophages were used as an in vitro model. Cells were pre-treated with NHDC for 1 h before stimulation with LPS (10 μg/ml) for 6 h. d -GalN/LPS markedly increased the serum transaminase activities and levels of oxidative and inflammatory markers, which were significantly attenuated by NHDC. Mechanistic analysis indicated that NHDC inhibited LPS-induced myeloid differentiation factor 88 (MyD88) and TIR-containing adapter molecule (TRIF)-dependent signaling. Transient transfection of TLR4 or MyD88 siRNA inhibited the downstream inflammatory signaling. This effect could also be achieved by the pretreatment with NHDC. The fluorescence microscopy and flow cytometry results suggested that NHDC potently inhibited the binding of LPS to TLR4 in RAW264.7 macrophages. In addition, the inhibitory effect of NHDC on LPS-induced translocation of TLR4 into lipid raft domains played an important role in the amelioration of production of downstream pro-inflammatory molecules. Furthermore, the activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) by NHDC inhibited TLR4 signaling. In conclusion, our results suggest that NHDC attenuates d -GalN/LPS-induced FHF by inhibiting the TLR4-mediated inflammatory pathway, demonstrating a new application of NHDC as a hepatoprotective agent.
研究领域:
免疫学
·
肝病学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 13
·3741-3750
·
IF 6.183
Song Zhang,Yiyun Cheng
Cytosolic protein delivery technique plays an important role in protein-based biotechnologies and therapeutics. However, the development of efficient nanocarriers for delivering cargo proteins into cytosols remains a continuing challenge due to the existence of multiple barriers. Here, we report an efficient strategy for the cytosolic delivery of native proteins by surface-engineered gold nanoparticles combined with hypertonicity treatment. Sub-10 nm gold nanoparticles stabilized by both cysteamine and 4-mercaptophenylboronic acid were used to complex cargo proteins via a combination of nitrogen-boronate coordination and ionic interactions. The yielding protein complexes with a size around 100 nm showed efficient endocytosis via micropinocytosis- and lipid raft-mediated pathways. Further the hypertonicity treatment of the transduced cells by glycerol, glucose, sucrose, and NaCl solutions efficiently facilitates the endosomal escape and the intracellular release of cargo proteins. By the proposed strategy, cargo proteins including bovine serum albumin, ovalbumin, green fluorescent protein, R-phycoerythrin, and horseradish peroxidase were successfully delivered into cell cytosol with maintained protein bioactivity. This study provides a feasible and efficient strategy for the intracellular protein delivery.
研究领域:
纳米技术
·
生物技术
·
治疗学
·
蛋白质工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）