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排序方式: 共有257条查询结果,搜索用时 15 毫秒
1.
Presentation of alpha-galactosylceramide by murine CD1d to natural killer T cells is facilitated by plasma membrane glycolipid rafts 下载免费PDF全文
CD1 molecules are non-polymorphic major histocompatibility complex class I-related proteins that bind and present glycolipid antigens to T-cell antigen receptors (TCR) expressed by alphabeta T cells or natural killer-like T cells (NKT). Anti-metastatic properties of NKT cells reactive to the CD1d-binding antigen alpha-galactosylceramide (alpha-GalCer) are now being explored as a contributor to tumour cell killing. In this study, we tested the hypothesis that presentation of alpha-GalCer by murine CD1d (mCD1d) to mCD1d-restricted NKT cells was facilitated by plasma membrane glycolipid rafts. Confocal microscopy of mCD1d-transfected A20 B cells (A20mCD1d) demonstrated that mCD1d was raft-localized. This observation was confirmed by immunoblotting of raft fractions isolated on sucrose density gradients. Raft disruption by the cholesterol-binding agent nystatin, or short-chain ceramides, inhibited presentation of low concentrations of alpha-GalCer to NKT cells. Inhibition of antigen presentation was reversed by treatment of A20mCD1d cells with higher alpha-GalCer concentrations, or removal of raft-disrupting agents. These data indicate that partitioning of mCD1d into membrane rafts increases the capacity of antigen-presenting cells to present limiting quantities of glycolipid antigens, perhaps by stabilizing mCD1d/antigen structures on the plasma membrane and optimizing TCR engagement on NKT cells. 相似文献
2.
Ishitsuka R Kobayashi T 《Anatomical science international / Japanese Association of Anatomists》2004,79(4):184-190
Sphingomyelin is a major sphingolipid species in animal cells and is a major lipid constituent of plasma membranes. Recent reports have established important roles for sphingomyelin and its metabolites as second messengers in signal transduction events during development and differentiation. Sphingomyelin is also a major component of sphingolipid, cholesterol-rich plasma membrane microdomains, known as 'lipid rafts'. However, little is known about the organization of sphingomyelin in biological membranes. Lysenin is a recently discovered sphingomyelin-specific toxin. In the present review, we summarize the current characterization of this protein and describe our recent attempt to elucidate the organization of sphingomyelin in cellular membranes using lysenin as a unique tool. 相似文献
3.
Cbl-b differentially regulates activation-induced apoptosis in T helper 1 and T helper 2 cells 总被引:2,自引:0,他引:2
We previously reported that ligation of CD3 induces antiapoptotic signals in T helper 2 (Th2) cells, and in contrast causes Th1 cells to undergo apoptosis. Here we show that Cbl-b is accountable for the unequal response, revealing a previously unknown cell-specific regulatory function for the molecule. Absence of Cbl-b resulted in resistance to activation-induced apoptosis in murine Th1 cells following CD3 ligation, akin to what is observed in Th2 cells containing Cbl-b. Concurrent with the apoptosis profile, CD3 ligation in the absence of Cbl-b induced raft mobilization and cytoskeletal rearrangement in Th1 cells. Despite their ability to signal from CD3, Th2 cells did not aggregate their rafts, providing an explanation for cell-specific activity of Cbl-b. 相似文献
4.
There is now considerable evidence suggesting that the plasma membrane of mammalian cells is compartmentalized by functional lipid raft microdomains. These structures are assemblies of specialized lipids and proteins and have been implicated in diverse biological functions. Analysis of their protein content using proteomics and other methods revealed enrichment of signalling proteins, suggesting a role for these domains in intracellular signalling. In T lymphocytes, structure/function experiments and complementary pharmacological studies have shown that raft microdomains control the localization and function of proteins which are components of signalling pathways regulated by the T-cell antigen receptor (TCR). Based on these studies, a model for TCR phosphorylation in lipid rafts is presented. However, despite substantial progress in the field, critical questions remain. For example, it is unclear if membrane rafts represent a homogeneous population and if their structure is modified upon TCR stimulation. In the future, proteomics and the parallel development of complementary analytical methods will undoubtedly contribute in further delineating the role of lipid rafts in signal transduction mechanisms. 相似文献
5.
多不饱和二十二碳六烯酸对白细胞介素-2α受体的抑制作用 总被引:3,自引:1,他引:3
目的:研究多不饱和二十二碳六烯酸(DHA)可通过改变IL-2a受体在细胞膜亚区域的分布和免疫抑制调节。方法:用DHA(22:6)处理Jurkat E6-1T细胞,硬脂酸(18:0)处理作为阴性对照。应用流式细胞仪检测DHA对T细胞表面分子CD25(IL-2Ra)表达的抑制作用。超速离心分离T细胞膜脂肪微区域,应用蛋白印迹法分析检测IL-2Ra所在的T细胞膜亚区域组分,与硬脂酸处理相比较,分析DHA处理对T细胞膜不同亚区域IL-2Ra分布的影响。结果:流式细胞仪检测表明,对照组75umol/L硬脂酸处理,检测到细胞表面CD25阳性表达细胞率为40.14%,75umol/LDHA处理T细胞,细胞表面CD25阳性表达细胞率为19.28%,DHA可抑制T细胞表面分子CD25的表达。蛋白印迹法分析确定IL-2Ra存在于rafts组分中,DHA处理使部分IL-2Ra从膜rafts区域移位到可溶膜区域。结论:膜脂肪微区域为IL-2受体信号转导的功能性亚区域,DHA通过调节IL-2Ra在膜脂肪微区域的分布,使部分IL-2Ra从功能性rafts区域移位到非功能性可溶膜区域,而产生免疫抑制作用。 相似文献
6.
目的 探讨Nogo-66受体(NgR)存神经元胞膜脂质筏中的定位。方法 利用免疫荧光双标法检测NgR和脂质筏特异标志物穴蛋白(Cavcolin)在培养的小脑颗粒神经元上的表达.并用Wcstcrn blot法检测以去垢剂法提取的脂质筏中NgR的表达。结果 免疫荧光双标显示NgR和Cavcolin的表达部化.Western blot分析发现脂质筏中NgR的表达为阳性。结论 在小脑颗粒神经元胞膜脂质筏中有NgR的表达.提示脂质筏有可能促进NgR的信号转导。 相似文献
7.
Complement component 1, q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF‐1/IGF‐1R signaling 下载免费PDF全文
Haojun Shi Winston Fang Minda Liu Deliang Fu 《International journal of cancer. Journal international du cancer》2017,141(7):1389-1401
Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor‐induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin‐like growth factor‐1 (IGF‐1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF‐1‐dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown. In the study, we demonstrated a significant association between C1QBP expression and hepatic metastasis in patients with pancreatic cancer. IGF‐1 induced the translocation of C1QBP from cytoplasm to lipid rafts and further drove the formation of CD44 variant 6 (CD44v6)/C1QBP complex in pancreatic cancer cells. C1QBP interacting with CD44v6 in lipid rafts promoted phosphorylation of IGF‐1R and thus activated downstream PI3K and MAPK signaling pathways which mediated metastatic potential of pancreatic cancer cells including proliferation, apoptosis, invasion, adhesion and energy metabolism. Furthermore, C1QBP knockdown suppressed hepatic metastasis of pancreatic cancer cells in nude mice. We therefore conclude that C1QBP in lipid rafts serves a key regulator of IGF‐1/IGF‐1R‐induced hepatic metastasis from pancreatic cancer. Our findings about C1QBP in lipid rafts provide a novel strategy to block IGF‐1/IGF‐1R signaling in pancreatic cancer and a reliable premise for more efficient combined modality therapies. 相似文献
8.
Yuyang Wang Yangyang Zhang Wei Zuo Zongyi Bo Chengcheng Zhang Xiaorong Zhang Yantao Wu 《Viruses》2022,14(10)
Caveolin-1 (Cav-1) is the basic component of caveolae, a specialized form of lipid raft that plays an essential role in endocytic viral entry. However, the evidence of direct involvement of caveolae and Cav-1 in avian reovirus (ARV) entry remains insufficient. In this study, the membrane lipid rafts were isolated as detergent-resistant microdomains (DRMs) by sucrose gradient centrifugation, and the capsid protein σB of ARV was found to associate with Cav-1 in DRMs fractions. Additionally, the interaction between ARV σB protein and Cav-1 was demonstrated by immunofluorescence co-localization and co-immunoprecipitation assays. Furthermore, we found that the internalization of ARV is sensitive to caveolae and dynamin inhibitors, while it is insensitive to clathrin inhibitors. In conclusion, these results indicate that the ARV σB protein interacts with Cav-1 during dynamin-dependent caveolae-mediated endocytosis for the entry of ARV. 相似文献
9.
Chia-Hung Chen Tzu-Hsiang Weng Kai-Yao Huang Hui-Ju Kao Kuang-Wen Liao Shun-Long Weng 《International journal of medical sciences》2022,19(14):2008
Endometrial cancer is one of the most common malignancy affecting women in developed countries. Resection uterus or lesion area is usually the first option for a simple and efficient therapy. Therefore, it is necessary to find a new therapeutic drug to reduce surgery areas to preserve fertility. Anticancer peptides (ACP) are bioactive amino acids with lower toxicity and higher specificity than chemical drugs. This study is to address an ACP, herein named Q7, which could downregulate 24-Dehydrocholesterol Reductase (DHCR24) to disrupt lipid rafts formation, and sequentially affect the AKT signal pathway of HEC-1-A cells to suppress their tumorigenicity such as proliferation and migration. Moreover, lipo-PEI-PEG-complex (LPPC) was used to enhance Q7 anticancer activity in vitro and efficiently show its effects on HEC-1-A cells. Furthermore, LPPC-Q7 exhibited a synergistic effect in combination with doxorubicin or paclitaxel. To summarize, Q7 was firstly proved to exhibit an anticancer effect on endometrial cancer cells and combined with LPPC efficiently improved the cytotoxicity of Q7. 相似文献
10.
Apatinib induces apoptosis of breast cancer cells by redistribution of Fas into lipid rafts 下载免费PDF全文
Apatinib, an oral anti-angiogenic agent, has been shown to have anti-cancer effects for several cancer cell types. However, little is known about the direct anti-tumor activity of apatinib for breast cancer cells. Herein, the direct effect of apatinib on breast cancer cells and its mechanism of action were assessed. Cell viability was measured with a Cell Counting Kit-8. Cell apoptosis was assessed by flow cytometry. The expression of caspase-8 and the cleavage of poly ADP ribose polymerase were assessed by Western blotting analysis. Lipid rafts and Fas distribution were determined by immunofluorescence microscopy. Apatinib suppressed breast cancer cell proliferation in a dose-dependent manner. Furthermore, apatinib enhanced the aggregation of lipid rafts and the redistribution of Fas into lipid rafts. Pretreatment with methyl-β-cyclodextrin, a cholesterol-sequestering agent, significantlyreversed Fas redistribution and apatinib-induced apoptosis.In conclusion, these results demonstrated that apatinib induced apoptosis of breast cancer cells partially through recruitment of Fas into lipid rafts. 相似文献