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 共查询到19条相似文献,搜索用时 31 毫秒
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一类新的第二信使——花生四烯酸脂氧合酶代谢物   总被引:1,自引:0,他引:1       下载免费PDF全文
海免感觉神经元对神经活性肽四肽FMRF酰胺的抑制性应答,是以花生四烯酸脂氧合酶代谢物为第二信使介导的。这类新的第二信使既可在胞内也可在胞问传递信号。同种离子通道(S通道)的开或关,受两种不同的第二信使系统调节控制。  相似文献   

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第二信使神经酰胺   总被引:5,自引:0,他引:5  
第二信使神经酰胺丁振华(第一军医大学基础部,广州510515)关键词第二信使神经酰胺鞘磷脂酶1995年,Boucher及其同事发现,在原代培养的小鼠脾T淋巴细胞中,CD28的信号传导能够通过鞘磷脂(sphingomylin)通路而活化核因子NF-κB...  相似文献   

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主要介绍获得诺贝尔生理学和医学奖的美国生物学家萨瑟兰的生平和发现第二信使的过程.以问题探究的脉络为线索,从站在巨人的肩膀上、科学研究需要知觉、机遇垂青于有准备的人、执著是科学家的品格4部分介绍萨瑟兰教授是如何找到科学研究的突破口,如何突破科学研究中的难点,如何锲而不舍地推进自己的科学研究,最终建立第二信使学说的过程.  相似文献   

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神经酰胺:细胞凋亡信号转号的第二信使分子   总被引:2,自引:0,他引:2  
神经酰胺是细胞凋亡信号调控中的一个第二信使因子,许多应激刺激能激活神经鞘磷脂循环产生神经酰胺诱导多种细胞体系发生凋亡。神经酰胺介导细胞凋亡的机理尚未完全明了,可能是通过多个下游靶分子包括CAPK,CAKK,PKC,SAPK/JNK,CPP32,Bcl-2以及Ras-RaclJNK/p38-K→GADD153信号传导链等作用于不同的信号转导途径而诱导细胞凋亡的。  相似文献   

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第二信使介导模拟低氧下丘脑CRF分泌   总被引:4,自引:0,他引:4  
用模拟高原低氧的方法研究急性低氧条件下促肾上腺皮质激素释放因子(corticotropin-releasingfactor,CRF)分泌的变化及第二信使参与CRF分泌的作用。低氧(海拔7km)1h后,正中隆起(medianeminence,ME)处CRF含量明显下降(P<0.05),下丘脑(hypothalamus,Hy)CRF(不含ME)含量无明显变化,而Hy内cAMP含量明显增加(P<0.01)。脑室注射Forsklin、TPA后低氧暴露(海拔5km)1h,MECRF含量下降(P<0.05;P<0.05),HyCRF无明显变化。脑室注射Forsklin后HycAMP含量升高(P<0.05)。脑室注射H7和PKA抑制剂,MECRF升高(P<0.05;P<0.01),HyCRF和HycAMP均无显著变化。上述结果表明急性低氧应激中CRF分泌显著增加,第二信使通路PKA和PKC通路均参与CRF分泌  相似文献   

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杜斌  孙建和 《微生物学报》2015,55(2):126-133
环二腺苷酸(cyclic diadenosine monophosphate,c-di-AMP)是在细菌中新发现的一种第二信使分子,其参与调节多种生理功能,包括细菌的生长、细胞壁的代谢平衡以及细菌的致病力等。c-di-AMP除了在细菌中发挥作用外,它还可作为第二信使分子被真核宿主识别,激活先天性免疫应答。细菌细胞内c-di-AMP的代谢受二腺苷酸环化酶(diadenylate cyclase,DAC)和磷酸二酯酶(phosphodiesterase,PDE)的调控。本文综述了c-di-AMP的代谢途径、调控机制、受体蛋白、生物学功能以及未来的研究方向和应用前景。  相似文献   

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微生物依赖信号识别和信号传递来感知并响应外界环境变化。c-di-AMP作为第二信使分子在信号传导过程中发挥着关键作用,其通过酶、转录调控因子和核糖开关等受体靶标来调控细胞生长、生物膜形成、K+稳态、DNA完整性、细胞壁合成和脂肪酸合成等与生理功能相关的基因和蛋白的表达。尽管对于c-di-AMP代谢调控在枯草芽孢杆菌、单增李斯特氏菌和金黄色葡萄球菌等细菌中的研究较为深入,但对其在乳酸菌中的研究却相对较少。基于此,文章重点关注乳酸菌中cdi-AMP的代谢及其在K+稳态和抑制甘氨酸甜菜碱转运中的信号传导作用;同时,通过总结现有研究中的乳酸菌c-di-AMP代谢调控,深化对乳酸菌第二信使分子信号调控的认知。  相似文献   

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The recognition of nucleic acids is a general strategy used by the host to detect invading pathogens. Many studies have established that MITA/STING is a central component in the innate immune response to cytosolic DNA and RNA derived from pathogens. MITA can act both as a direct sensor of cyclic dinucleotides (CDNs) and as an adaptor for the recruitment of downstream signaling components. In both roles, MITA is part of signaling cascades that orchestrate innate immune defenses against various pathogens, including viruses, bacteria and parasites. Here, we highlight recent studies that have uncovered the molecular mechanisms of MITA-mediated signal transduction and regulation, and discuss some notable issues that remain elusive.  相似文献   

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The host takes use of pattern recognition receptors (PRRs) to defend against pathogen invasion or cellular damage. Among microorganism-associated molecular patterns detected by host PRRs, nucleic acids derived from bacteria or viruses are tightly supervised, providing a fundamental mechanism of host defense. Pathogenic DNAs are supposed to be detected by DNA sensors that induce the activation of NFκB or TBK1-IRF3 pathway. DNA sensor cGAS is widely expressed in innate immune cells and is a key sensor of invading DNAs in several cell types. cGAS binds to DNA, followed by a conformational change that allows the synthesis of cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) from adenosine triphosphate and guanosine triphosphate. cGAMP is a strong activator of STING that can activate IRF3 and subsequent type I interferon production. Here we describe recent progresses in DNA sensors especially cGAS in the innate immune responses against pathogenic DNAs.  相似文献   

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S-palmitoylation is a reversible posttranslational lipid modification of proteins. It controls protein activity, stability, trafficking and protein–protein interactions. Recent global profiling of immune cells and targeted analysis have identified many S-palmitoylated immunity-associated proteins. Here, we review S-palmitoylated immune receptors and effectors, and their dynamic regulation at cellular membranes to generate specific and balanced immune responses. We also highlight how this understanding can drive therapeutic advances to pharmacologically modulate immune responses.  相似文献   

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Cyclic GMP‐AMP synthase (cGAS) is activated by ds‐DNA binding to produce the secondary messenger 2′,3′‐cGAMP. cGAS is an important control point in the innate immune response; dysregulation of the cGAS pathway is linked to autoimmune diseases while targeted stimulation may be of benefit in immunoncology. We report here the structure of cGAS with dinucleotides and small molecule inhibitors, and kinetic studies of the cGAS mechanism. Our structural work supports the understanding of how ds‐DNA activates cGAS, suggesting a site for small molecule binders that may cause cGAS activation at physiological ATP concentrations, and an apparent hotspot for inhibitor binding. Mechanistic studies of cGAS provide the first kinetic constants for 2′,3′‐cGAMP formation, and interestingly, describe a catalytic mechanism where 2′,3′‐cGAMP may be a minor product of cGAS compared with linear nucleotides.  相似文献   

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The mimicking of olfaction is considered to be a promising approach for the construction of artificial odour-sensing systems. In the nose, the detection of volatile odorants begins when the odorant ligands interact with specific odorant receptors in the ciliary membrane of the olfactory neurons. A large family of genes encoding putative odorant receptors has been identified recently. Individual receptor types are expressed in subsets of cells distributed in distinct zones of the olfactory epithelium. Ligand-receptor interaction triggers a rapid multistep reaction cascade, resulting in a “pulse” of second messengers that initiates an electrical response from the receptor neuron. Olfactory signalling is terminated by phosphorylation of receptors via a negative feedback reaction, catalyzed by specific kinases.  相似文献   

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This essay attempts to summarize some of the best evidence for the role of inositol trisphosphate as a second messenger in signal transduction processes. The following aspects are addressed in the essay: (a) The synthesis of inositol trisphosphate and other inositol lipids, (b) Receptor-phosphatidylinositol bisphosphate phospholipase C coupling and the N-ras protooncogene, (c) Inositol trisphosphate and intracellular calcium, (d) Cell growth and oncogenes, (e) Receptors linked to the phosphatidylinositol cycle, (f) Phototransduction and (g) Interactions between inositol trisphosphate and other second messengers.Abbreviations Cyclic AMP Adenosine 3,5-cyclic monophosphate - Cyclic GMP Guanosine 3,5-cyclic monophosphate - DG sn, 1,2-Diacylglycerol - EGF Epidermal growth factor - GDP Guanosine diphosphate - GTP Guanosine triphosphate - IP Inositol 1-monophosphate - IP2 Inositol 1,4-diphosphate - IP3 Inositol 1,4,5-trisphosphate - PA Phosphatidic acid - PDGF Platelet-derived growth factor - PI Phosphatidylinositol - PIP Phosphatidylinositol 4-monophosphate - PIP2 Phosphatidylinositol 4,5-bisphosphate - PIP3 Phosphatidylinositol 3,4,5-trisphosphate - PLC Phospholipase C  相似文献   

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环二鸟苷酸——新型的细菌第二信使   总被引:1,自引:0,他引:1  
环二鸟苷酸(cyclic diguanylate,c-di-GMP)是新近发现的在细菌中普遍存在的第二信使分子,参与调节多种生理功能,包括细胞分化、从运动状态到生物被膜状态的转变、致病因子产生等.基于其对细菌抗生素耐药的物理屏障—生物被膜形成的影响,c-di-GMP的研究越来越受到人们的关注.细胞内c-di-GMP的产生受二鸟苷酸环化酶(diguanylate cyclase,DGC)合成和磷酸二酯酶(phosphodiesterase,PDE)降解两条途径调控.在结构上,通常DGC含有GGDEF结构域,PDE含有EAL结构域.c-di-GMP的作用靶点包括PilZ结构域和GEMM 核开关两种类型.本文综述了c-di-GMP的代谢途径、调控机理、生物学功能等方面的最新研究进展,并对c-di-GMP在今后研究中的应用和发展趋势进行展望.  相似文献   

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The foetus can be regarded as a half-allograft implanted into the maternal body. In a successful pregnancy, the mother does not reject the foetus because of the immune tolerance mechanism at the maternal-foetal interface. The innate immune cells are a large part of the decidual leukocytes contributing significantly to a successful pregnancy. Although the contributions have been recognized, their role in human pregnancy has not been completely elucidated. Additionally, the accumulated evidence demonstrates that the immune checkpoint molecules expressed on the immune cells are co-inhibitory receptors regulating their activation and biological function. Therefore, it is critical to understand the immune microenvironment and explore the function of the innate immune cells during pregnancy. This review summarizes the classic immune checkpoints such as PD-1, CTLA-4 and some novel molecules recently identified, including TIM-3, CD200, TIGIT and the Siglecs family on the decidual and peripheral innate immune cells during pregnancy. Furthermore, it emphasizes the role of the immune checkpoint molecules in pregnancy-associated complications and reproductive immunotherapy.  相似文献   

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Dimeric class II aspartyl-tRNA synthetase (AspRS) from yeast has a modular architecture and includes an N-terminal appendix of 70 amino acid residues that protrudes from the anticodon-binding module. This extension, of predicted helical structure, is not essential for aminoacylation but contains an RNA-binding motif that promotes non-specific interactions with tRNAs. As shown here, this protein extension can also interact with the 5' end of the AspRS mRNA. In vitro, optimal binding occurs on an mRNA domain comprising part of the 87 nucleotide long 5'UTR and the sequence encoding the N-terminal appendix. At the protein side, only the appendix and the anticodon-binding module participate in the interaction between AspRS and the mRNA domain. Binding is specific, since only tRNA(Asp) can dissociate the complex. In vivo, AspRS also binds specifically this mRNA domain and in doing so triggers a reduced translation of a fused GFP mRNA. From that, a mechanism for the regulation of this eukaryotic aminoacyl-tRNA synthetase is proposed. Implications for aspartylation accuracy in yeast are given.  相似文献   

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