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Xinyu Dou Yunlong Ma Qipeng Luo Chunyu Song Meijuan Liu Xiao Liu Donglin Jia Shuiqing Li Xiaoguang Liu 《Journal of cellular and molecular medicine》2023,27(16):2340-2353
Ferroptosis, a novel type of cell death mediated by the iron-dependent lipid peroxidation, contributes to the pathogenesis of the intervertebral disc degeneration (IDD). Increasing evidence demonstrated that melatonin (MLT) displayed the therapeutic potential to prevent the development of IDD. Current mechanistic study aims to explore whether the downregulation of ferroptosis contributes to the therapeutic capability of MLT in IDD. Current studies demonstrated that conditioned medium (CM) from the lipopolysaccharide (LPS)-stimulated macrophages caused a series of changes about IDD, including increased intracellular oxidative stress (increased reactive oxygen species and malondialdehyde levels, but decreased glutathione levels), upregulated expression of inflammation-associated factors (IL-1β, COX-2 and iNOS), increased expression of key matrix catabolic molecules (MMP-13, ADAMTS4 and ADAMTS5), reduced the expression of major matrix anabolic molecules (COL2A1 and ACAN), and increased ferroptosis (downregulated GPX4 and SLC7A11 levels, but upregulated ACSL4 and LPCAT3 levels) in nucleus pulposus (NP) cells. MLT could alleviate CM-induced NP cell injury in a dose-dependent manner. Moreover, the data substantiated that intercellular iron overload was involved in CM-induced ferroptosis in NP cells, and MLT treatment alleviated intercellular iron overload and protected NP cells against ferroptosis, and those protective effects of MLT in NP cells further attenuated with erastin and enhanced with ferrostatin-1(Fer-1). This study demonstrated that CM from the LPS-stimulated RAW264.7 macrophages promoted the NP cell injury. MLT alleviated the CM-induced NP cell injury partly through inhibiting ferroptosis. The findings support the role of ferroptosis in the pathogenesis of IDD, and suggest that MLT may serve as a potential therapeutic approach for clinical treatment of IDD. 相似文献
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Gene P. Ables Kryscilla Jian Zhang Yang Silke Vogel Antonio Hernandez-Ono Shuiqing Yu Jason J. Yuen Susan Birtles Linda K. Buckett Andrew V. Turnbull Ira J. Goldberg William S. Blaner Li-Shin Huang Henry N. Ginsberg 《Journal of lipid research》2012,53(11):2364-2379
Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 catalyzes the final step oftriglyceride (TG) synthesis. We show that acute administration of a DGAT1 inhibitor(DGAT1i) by oral gavage or genetic deletion of intestinal Dgat1(intestine-Dgat1−/−)markedly reduced postprandial plasma TG and retinyl ester excursions by inhibitingchylomicron secretion in mice. Loss of DGAT1 activity did not affect the efficiencyof retinol esterification, but it did reduce TG and retinoid accumulation in thesmall intestine. In contrast, inhibition of microsomal triglyceride transfer protein(MTP) reduced chylomicron secretion after oral fat/retinol loads, but withaccumulation of dietary TG and retinoids in the small intestine. Lack of intestinalaccumulation of TG and retinoids in DGAT1i-treated orintestine-Dgat1−/− miceresulted, in part, from delayed gastric emptying associated with increased plasmalevels of glucagon-like peptide (GLP)-1. However, neither bypassing the stomachthrough duodenal oil injection nor inhibiting the receptor for GLP-1 normalizedpostprandial TG or retinyl esters excursions in the absence of DGAT1 activity. Insummary, intestinal DGAT1 inhibition or deficiency acutely delayed gastric emptyingand inhibited chylomicron secretion; however, the latter occurred when gastricemptying was normal or when lipid was administered directly into the small intestine.Long-term hepatic retinoid metabolism was not impacted by DGAT1 inhibition. 相似文献
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转录因子E2F1和PCNA在分离、培养的人视网膜色素上皮细胞中的表达及意义 总被引：3，自引：0，他引：3
为探讨转录因子 E2 F1及增殖细胞核抗原 (PCN A)在增生性玻璃体视网膜病变 (PVR)中的作用 ,采用 SABC免疫细胞化学法检测转录因子 E2 F1和 PCNA在无血清组及 2 0 %血清组培养的人视网膜色素上皮细胞 (RPE)中的表达。结果显示在无血清组中 ,转录因子 E2 F1表达的阳性率为 2 .4%± 0 .2 5 % ,而未见 PCNA表达 ;在 2 0 %血清组中 ,E2 F1及 PCNA的表达阳性率分别为 2 9.1%± 0 .71%和 48.6 %± 1.13%。说明 E2 F1和 PCNA蛋白的表达取决于人 RPE细胞的生长状态 ,在增殖活跃的细胞中表达增高 ;转录因子 E2 F1调控人 RPE细胞中 PCNA蛋白的表达。提示转录因子 E2 F1调控人 RPE细胞的细胞周期进展 ,在 PVR的形成中也发挥着关键性的作用 相似文献
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Hermann Schillers Izhar Medalsy Shuiqing Hu Andrea L. Slade James E. Shaw 《Journal of molecular recognition : JMR》2016,29(2):95-101
Microvilli are a common structure found on epithelial cells that increase the apical surface thus enhancing the transmembrane transport capacity and also serve as one of the cell's mechanosensors. These structures are composed of microfilaments and cytoplasm, covered by plasma membrane. Epithelial cell function is usually coupled to the density of microvilli and its individual size illustrated by diseases, in which microvilli degradation causes malabsorption and diarrhea. Atomic force microscopy (AFM) has been widely used to study the topography and morphology of living cells. Visualizing soft and flexible structures such as microvilli on the apical surface of a live cell has been very challenging because the native microvilli structures are displaced and deformed by the interaction with the probe. PeakForce Tapping® is an AFM imaging mode, which allows reducing tip–sample interactions in time (microseconds) and controlling force in the low pico‐Newton range. Data acquisition of this mode was optimized by using a newly developed PeakForce QNM‐Live Cell probe, having a short cantilever with a 17‐µm‐long tip that minimizes hydrodynamic effects between the cantilever and the sample surface. In this paper, we have demonstrated for the first time the visualization of the microvilli on living kidney cells with AFM using PeakForce Tapping. The structures observed display a force dependence representing either the whole microvilli or just the tips of the microvilli layer. Together, PeakForce Tapping allows force control in the low pico‐Newton range and enables the visualization of very soft and flexible structures on living cells under physiological conditions. © 2015 The Authors Journal of Molecular Recognition Published by John Wiley & Sons Ltd. 相似文献
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立德树人是教育事业的根本任务,课程思政是将立德树人融入教育各环节、各领域的重要手段。"细胞生物学"既是现代生命科学的前沿分支学科之一,也是高校生命科学类专业的重要课程。该文在课程思政的背景下,选择新型冠状病毒肺炎疫情(简称:新冠疫情)为载体,以"细胞生物学"课程中"病毒的特征、入侵、增殖"为主线,从"教学内容的甄选"和"实施策略"两个方面着手,开展聚焦新冠疫情下"细胞生物学"课程思政教学的深入探讨。该研究旨在引导学生在研习专业知识的基础上,提升其科学素养、树立其正确的价值观,为侧重新冠疫情的课程思政研究提供重要参考。 相似文献
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为探讨GPER基因的活化对人乳腺癌相关成纤维细胞(CAF)有氧糖酵解的影响,本研究构建GPERsi RNA慢病毒,转染CAF细胞,以构建GPER敲低的稳定细胞系;对照组(CAF-shNC)和GPER-shRNA慢病毒感染组(CAF-shGPER组),经嘌呤霉素筛选后,实时荧光定量PCR和蛋白印迹法检测GPER的m RNA及蛋白的表达;用GPER特异性激动剂G1 (1μmol/L)处理以上两组细胞,得到G1+CAF-shNC和G1+CAFsh GPER,应用蛋白印迹法分别检测以上4组细胞中GPER下游基因p-PKA和p-CREB的表达;采用实时荧光定量PCR和蛋白印迹法检测CREB糖酵解相关靶基因PDK4和LDHB的表达,应用葡萄糖、乳酸检测试剂盒检测4组细胞中葡萄糖消耗,乳酸生成情况。最终,成功构建GPER敲低的CAF稳定细胞系;GPER特异性激动剂G1可明显上调CAF-shNC组中GPER mRNA和蛋白水平;G1+CAF-shNC与CAF-shNC和G1+CAFsh GPER组相比,GPER下游基因PKA和CREB的磷酸化水平显著增加(p<0.05);CREB糖酵解相关靶基因PDK4和LDHB的mRNA和蛋白水平明显上调(p<0.05);葡萄糖消耗量和乳酸生成量明显增加(p<0.05)。由此可得,在人乳腺癌相关成纤维细胞中,GPER特异性激动剂G1活化GPER促进CAF的有氧糖酵解。 相似文献
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Fusobacterium nucleatum is one of the most abundant gram-negative bacilli colonizing the subgingival plaque and closely associated with periodontal disease. However it is unclear whether F. nucleatum is involved in gingival inflammation under orthodontic appliance. A novel adhesin, FadA, which is unique to oral Fusobacteria, is required for F. nucleatum binding and invasion to epithelial cells and thus may play an important role in colonization of Fusobacterium in the host. In this study, we evaluated the prevalence of F. nucleatum and its virulence factor FadA adhesion gene (fadA) in 169 subgingival biofilm samples from 55 cases of gingivitis patients with orthodontic appliances, 49 cases of gingivitis patients without orthodontic treatment, 35 cases of periodontitis patients and 30 cases of periodontally healthy people via PCR. The correlations between the F. nucleatum/fadA and gingivitis index(GI)was also analyzed. The detection rate of F. nucleatum/fadA in periodontitis group and non-orthodontic gingivitis group was higher than the other two groups (p<0.01) while it was higher in orthodontic gingivitis group than in health people (p<0.05). An obviously positive correlation was observed between the prevalence of F. nucleatum/fadA and GI. F. nucleatum carrying fadA may be more closely related to the development of gingivitis and periodontal disease compared with orthodontic gingivitis. 相似文献