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Vitamin K2: A Vitamin that Works like a Hormone, Impinging on Gene Expression 维生素K2:一种像激素一样作用的维生素,影响基因表达
Pub Date : 2019-04-17 DOI: 10.5772/INTECHOPEN.80388
J. Gordeladze
Vitamin K2 binds to the intranuclear receptor SXR and results in the activation of a pleth- ora of genes, both directly and indirectly. Among these genes are important biological markers of cellular characteristics or features (also known as cell phenotypes), as well as a set of molecules known to be involved in both hormone-induced, G-protein-mediated cell signalling, either directly or indirectly activating so-called sirtuins and/or histone deacetylaces (HDACs), known as determinants of cell types and their specific functions in a given tissue. Hence, vitamin K2 may be closely involved in or serving as a traditional molecular ‘link’ between hormonal receptors and intracellular signalling pathways. It has been stated that a true hormone is a product of living cells, which circulates in body fluids (such as blood) and elicits a specific and often stimulatory effect on the activity of cells situated remotely from its point of origin. A large bulk of evidence published over the past 10 years establishes vitamin K2 in this category of substances. Hence, vitamin K2 should be considered and consequently classified as a hormone.
维生素K2与核内受体SXR结合,直接或间接地激活大量基因。在这些基因中,有细胞特征或特征(也称为细胞表型)的重要生物学标记,以及一组已知参与激素诱导的、g蛋白介导的细胞信号传导的分子,这些分子直接或间接激活所谓的sirtuins和/或组蛋白去乙酰化酶(hdac),它们被称为细胞类型及其在给定组织中的特定功能的决定因素。因此,维生素K2可能密切参与或作为激素受体和细胞内信号通路之间的传统分子“链接”。有人指出,真正的激素是活细胞的产物,它在体液(如血液)中循环,并对远离其来源的细胞的活动产生特定的、往往是刺激的作用。过去10年发表的大量证据将维生素K2确定为这一类物质。因此,维生素K2应该被认为是一种激素。
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引用次数: 2
The Signaling Nature of Cellular Metabolism: The Hypoxia Signaling 细胞代谢的信号性质:缺氧信号
Pub Date : 2018-11-28 DOI: 10.5772/INTECHOPEN.79952
Z. Fábián
Identification of the hypoxia-inducible factors (HIFs) as core players of the transcriptional response to hypoxia transformed our understanding of the mechanism underpinning the hypoxic response at the molecular level and led to discoveries on the role of metabolism in cell signaling alike. It has now become clear that HIFs act in the heart of a pathway where oxygen may be considered as a signaling entity recognized by molecular sensors conveying the oxygen signal to the transcriptional regulator HIFs as distal effectors. The pathway is under multiple levels of regulatory control shaping the cellular response to hypoxia and gives hypoxia signaling an intricate and dynamic activity profile. These include regulatory mechanisms within the HIF pathway as well as diverse interplay with other metabolic and signaling pathways of critical cellular functions. The emerging model reflects a multi-level regulatory network that apparently affects all aspects of cell physiology.
缺氧诱导因子(hif)作为缺氧转录反应的核心参与者的发现,改变了我们对分子水平上支撑缺氧反应机制的理解,并导致了代谢在细胞信号传导中的作用的发现。现在已经清楚的是,hif在一个通路的中心起作用,其中氧可以被认为是一个信号实体,由分子传感器识别,将氧信号传递给转录调节因子hif作为远端效应器。该通路在多个水平的调控下形成细胞对缺氧的反应,并赋予缺氧信号一个复杂而动态的活动概况。这些包括HIF通路内的调节机制以及与其他关键细胞功能的代谢和信号通路的多种相互作用。新出现的模型反映了一个多层次的调控网络,显然影响细胞生理学的各个方面。
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引用次数: 1
Wnt Signaling as a Master Regulator of Immune Tolerance in a Tumor Microenvironment Wnt信号作为肿瘤微环境中免疫耐受的主要调节因子
Pub Date : 2018-11-12 DOI: 10.5772/INTECHOPEN.81619
M. C. Castañeda-Patlán, Gabriela Fuentes-García, M. Robles-Flores
Aberrant Wnt signaling is a hallmark of many cancer types such as colon cancer. However, the effect of altered Wnt signaling is not only restricted to cancer cells but also dynami cally interacts with a tumor microenvironment and has the ability to directly regulate the anti-tumor immune response. It has been reported that tumors induce immune tolerance through the activation of canonical Wnt signaling in dendritic cells promoting T regula - tory responses, and also that both canonical and noncanonical Wnt proteins program dendritic cell responses for tolerance. Thus, the Wnt signaling pathway may be a novel and promising therapeutic target for anticancer immunotherapy. In this review, we will discuss the molecular mechanisms involved in immune cell response regulation medi - ated by canonical and noncanonical Wnt signaling. C (PLC) to produce diacylglycerol and Ca 2+ mobilization that activates PKC isoforms, other Ca 2+ -modulated kinases and calcineurin phosphatase, which in turn promotes NFAT translocation to the nucleus.
异常的Wnt信号是许多癌症类型的标志,如结肠癌。然而,Wnt信号改变的作用不仅局限于癌细胞,还与肿瘤微环境动态相互作用,具有直接调节抗肿瘤免疫应答的能力。据报道,肿瘤通过激活树突状细胞中的典型Wnt信号来诱导免疫耐受,促进T调节反应,并且典型和非典型Wnt蛋白都可以编程树突状细胞的耐受反应。因此,Wnt信号通路可能是抗癌免疫治疗的一个新的有前途的治疗靶点。在这篇综述中,我们将讨论典型和非典型Wnt信号介导的免疫细胞反应调节的分子机制。C (PLC)产生二酰基甘油和ca2 +动员,激活PKC异构体、其他ca2 +调节的激酶和钙调磷酸酶,进而促进NFAT转运到细胞核。
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引用次数: 6
A Novel Genetic Circuit Supports Laboratory Automation and High Throughput Monitoring of Inflammation in Living Human Cells 一个新的遗传电路支持实验室自动化和高通量监测炎症在活的人类细胞
Pub Date : 2018-11-05 DOI: 10.5772/INTECHOPEN.78568
Natalie Duong, Kevin J. Curley, M. A. Do, Daniel Levy, Biao Lu
Genetically encoded reporter circuits have been revolutionizing our ability to monitor, manipulate, and visualize specific cellular responses to a variety of environmental stimuli. However, the development of genetic circuits that enable both high throughput (HTP) application and laboratory automation remains challenging. In this report, we describe a novel dual-reporter circuit that utilizes a secretory Gaussia luciferase (Gluc) and a green fluorescent protein (GFP) for monitoring inflammatory signaling, a fundamental process in many life events. We designed and built this genetic circuit into a simple adeno-associated viral (AAV) vector, which is suitable for both simple transfection and efficient transduction protocols. We demonstrated high sensitivity and specificity of this new circuit and its ability to monitor a broad range of inflammatory response in various human cell models. Impor-tantly, this novel system is simple, robust, and readily adaptable to HTP applications and laboratory automation including fluorescence activated cell sorting (FACS) and microplate reader analysis. By combining both GFP and Gluc in one genetic circuit, our new dual- reporter circuit provides an easy and powerful tool for monitoring and quantifying inflammatory signals in various mammalian cells.
基因编码的报告电路已经彻底改变了我们对各种环境刺激的特定细胞反应的监测、操纵和可视化能力。然而,使高通量(HTP)应用和实验室自动化的遗传电路的发展仍然具有挑战性。在本报告中,我们描述了一种新的双报告电路,利用分泌的高斯荧光素酶(Gluc)和绿色荧光蛋白(GFP)来监测炎症信号,这是许多生命事件的基本过程。我们设计并构建了一个简单的腺相关病毒(AAV)载体,该载体适用于简单的转染和高效的转导方案。我们证明了这种新回路的高灵敏度和特异性,以及它在各种人类细胞模型中监测广泛炎症反应的能力。重要的是,这种新系统简单,坚固,易于适应HTP应用和实验室自动化,包括荧光活化细胞分选(FACS)和微孔板读取器分析。通过将GFP和Gluc结合在一个遗传回路中,我们的新双报告电路为监测和量化各种哺乳动物细胞中的炎症信号提供了一种简单而强大的工具。
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引用次数: 0
Information Thermodynamics of Cell Signal Transduction 细胞信号转导的信息热力学
Pub Date : 2018-11-05 DOI: 10.5772/INTECHOPEN.79951
T. Tsuruyama
Intracellular signal transduction is the most important research topic in cell biology, and for many years, model research by system biology based on network theory has long been in progress. This article reviews cell signaling from the viewpoint of information thermo- dynamics and describes a method for quantitatively describing signaling. In particular, a theoretical basis for evaluating the efficiency of intracellular signal transduction is presented in which information transmission in intracellular signal transduction is maxi-mized by using entropy coding and the fluctuation theorem. An important conclusion is obtained: the average entropy production rate is constant through the signal cascade.
细胞内信号转导是细胞生物学中最重要的研究课题,多年来,基于网络理论的系统生物学模型研究早已展开。本文从信息热力学的角度对细胞信号传导进行了综述,并描述了一种定量描述信号传导的方法。特别提出了一种评价细胞内信号转导效率的理论基础,利用熵编码和涨落定理使细胞内信号转导中的信息传递最大化。得到了一个重要的结论:通过信号级联,平均熵产生率是恒定的。
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引用次数: 0
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