昆虫基因表达的调控

昆虫的基因表达过程十分复杂,受多种调控因子的调节,随着分子生物学研究新技术在昆虫学上的应用,昆虫基因表达的调控也取得了较快进展,本文以一些特征清楚的系统为例,讨论昆虫基因表达调控的研究现状,旨在为其它昆虫表达的调控研究提供借鉴。     

昆虫变态发育类型与调控机制

昆虫变态发育使得昆虫成为地球上种类最多、分布最广的动物种群。它特指末龄幼虫化蛹,或者蛹向成虫的转变过程。根据变态剧烈程度,可将昆虫变态发育简单分为增节变态、表变态、原变态、不完全变态及全变态5种类型。此外,昆虫变态发育是一个极其复杂的生物学过程,受到激素、基因、营养等多种因素的精密调控。本文简要介绍了昆虫变态发育的类型和分子调控机理方面的研究进展。     

多发性骨髓瘤的生长调控机制

多发性骨髓瘤（Multiple myeloma,MM）是一种目前仍无法治愈的血液系统恶性肿瘤。其发生、发展与细胞因子、体内微环境以及癌基因产物等多种作用因素密切相关。本文将分别阐述影响MM细胞生存和生长的控制因子及其作用机制。     

mTOR信号通路与细胞生长调控

mTOR （the ammalian target of mpamycin）是一个进化上十分保守的蛋白激酶,属于PIKK（the phosphatidylinsoitol kinase—related kinase）超家族,作为Ser/Thr激酶而起作用。它可以汇聚和整合来自于营养、生长因子、能量和环境压力对细胞的刺激信号,进而通过下游效应器（4EBPl和S6Ks）调节细胞生长。mTOR信号通路还影响胚胎干细胞和早期胚胎的发育,并且与肿瘤、肥胖及代谢紊乱等疾病有关。对mTOR信号通路的生理功能、分子组成和调节机制的研究不仅可以深入了解细胞生长调控的机制,而且对于相关疾病的治疗具有重要意义。     

昆虫卵子发生调控机制的研究进展

卵子发生是昆虫生殖过程中的关键环节,它不仅确保了种群的繁衍和遗传信息的传递,还与昆虫的适应性进化和社会结构的形成密切相关。本文概述了调控卵子发生的机制,包括形态学变化、功能意义以及多种影响因素。形态学上,卵子发生涉及从原始生殖细胞发育为成熟卵母细胞的连续过程,这一过程在不同昆虫中有所差异。影响因素上包括激素调控机制的多样性、环境和营养因素如何精细调控生殖过程,以及非激素因素如MicroRNA、转录因子、免疫信号和微生物代谢在卵子发生中的作用。内分泌激素,特别是保幼激素和蜕皮激素,在卵子发生中发挥核心作用,它们通过调节生殖干细胞的自我更新、卵母细胞成熟和营养供给等关键环节来调控卵子发生。不同昆虫中这些激素的作用机制存在差异,反映了昆虫在生殖调控上的多样性。除了激素调控,环境和营养因素也通过影响内分泌或神经系统对卵子发生产生影响。气候变化、营养状况等外部条件可以改变昆虫的生殖策略,从而影响种群的适应性和生存。此外,MicroRNA和转录因子在基因表达调控和细胞命运决定中扮演关键角色,而免疫信号和微生物代谢与卵子发生的相互作用也逐渐成为研究的焦点。本文旨在为理解昆虫卵子发生的复杂调控网络提供了全面的视角,并指出了未来研究潜在方向。     

昆虫体色多型的分子调控机制

体色多型普遍存在于各昆虫类群,体色多型不仅是生物多样性的体现,而且多样的着色模式对于昆虫本身具有重要的生物学意义.研究体色多型对探讨昆虫遗传多态性、适应机制及生物进化等具有重要的意义.本文主要从昆虫体色多型的分子调控机制进行综述,以期为今后探讨昆虫多态性、适应机制及生物进化提供参考.     

贴壁培养方式中昆虫细胞的生长限制性因素研究

以昆虫细胞为宿主生产病毒杀虫剂或进行基因工程产品的开发,是动物细胞培养领域十分有吸引力的研究方向。近年来,昆虫细胞的体外培养尽管在培养条件的优化⑴、培养基的开发⑵以及工艺癍程的设计⑶等诸多方面取得了令人鼓舞的进展,但由于对影响细胞生长及代谢的各类限制性因素尚缺乏全面系统的了解,因而目前的技术水平还远不能设计出优化的培养系统以满足产业化的需要。众所周知,细胞的生长和产物的形成是多种环境因素和细胞内复杂代谢反应的综合结果,因此。对生长限制性因素的考察也应有全局观念,即：在重视生化环境(外因)对细胞培养过程影响的同时,也不能忽视细胞株自身性能(内因)对最终培养结果的影响。以往的研究〔4.5〕大多仅就个别营养限制性因素进行孤立地探讨,缺乏从内外因两方面对昆虫细胞培养过程的认识。最近,以微载体技术或堆积床技术贴壁培养昆虫细胞业已证明具有很大的发展前途〔6.7〕。为此．本文以贴壁培养的秋黏虫细胞(IPLB-Sf2l—AE)和粉蚊夜蛾细胞(BTI—Tn一5Bl-4)为研究对象,在考察环境限制性因素的同时,亦从细胞自身特点出发考察了不同细胞株的生长及代谢性能。研究结果可望为贴壁培养技术的深入应用以及培养过程的合理设计提供参考。     

昆虫种群的遗传调控

昆虫种群的遗传调控是利用昆虫自身生长发育的关键基因,采用性别控制开关,通过遗传转化使雄虫成为携带导致后代雌虫发育异常或雌性不育的遗传控制复合体（性别开关元件和靶标基因的复合体）．昆虫种群遗传调控是一种基于不育技术的昆虫种群控制系统,具有种类特异、环境友好和便捷高效等特点．目前为止,已经由早期的通过辐射不育方法发展到释放携带显性致死基因昆虫的方法,并在多种昆虫中获得成功．本文综述了昆虫种群遗传调控的发展历程,介绍了昆虫种群遗传调控相关的理论与方法,包括特异的调控元件、致死或缺陷基因和遗传转化体系的应用,并列举了几种昆虫种群遗传调控的实例,最后对于昆虫种群遗传调控系统中存在的问题以及可能的发展方向进行了展望．     

多胺调控细胞生长机制的研究进展

多胺(腐胺、精脒、精胺)是真核细胞体内重要的多聚阳离子,对细胞的生长增殖发挥重要作用。快速生长的细胞内含有高浓度的多胺,降低多胺含量将抑制细胞的生长,阻滞细胞周期,而升高多胺含量则会促进细胞快速生长增殖。对多胺的调控已经成为研究细胞生长增殖调控的切入点之一。     

Acid β-Glucosidase: Enzymology and Molecular Biology of Gaucher Diseas

Abstract

Human lysosomal β-glucosidase (D-glucosyl-acylsphingo-sine glucohydrolase, EC 3.2.1.45) is a membrane-associated enzyme that cleaves the β-glucosidic linkage of glucosylcer-amide (glucocerebroside), its natural substrate, as well as synthetic β-glumsides. Experiments with cultured cells suggest that in vivo this glycoprotein requires interaction with negatively charged lipids and a small acidic protein, SAP-2, for optimal glucosylceramide hydrolytic rates. In vitro, detergents (Triton? X-100 or bile acids) or negatively charged gangliosides or phos-pholipids and one of several “activator proteins” increase hydrolytic rate of lipid and water-soluble substrates. Using such in vitro assay systems and active site-directed covalent inhibitors, kinetic and structural properties of the active site have been elucidated. The defective activity of this enzyme leads to the variants of Gaucher disease, the most prevalent lysosomal storage disease. The nonneuronopathic (type 1) and neuronopathic (types 2 and 3) variants of this inherited (autosomal recessive) disease but panethnic, but type 1 is most prevalent in the Ashkenazi Jewish population. Several missense mutations, identified in the structural gene for lysosomal β-glucosidase from Gaucher disease patients, are presumably casual to the specifically altered post-translational oligosaccharide processing or stability of the enzyme as well as the alterecA in vitro kinetic properties of the residual enzyme from patient tissues.     

类胰岛素生长因子-Ⅰ和胰岛素表现其功能的结构和分子基础

综述了近年来关于IGF-Ⅰ和胰岛素表现生理功能的结构基础和分子基础研究进展.IGF-Ⅰ和胰岛素是胰岛素家族中的2个重要成员, 两者的分子结构高度同源, 两者的受体相似且属同一家族, 两者的生理功能可彼此交叉, 但各自具有主要的生理功能.IGF-Ⅰ的主要生理功能是促进细胞生长, 胰岛素的主要生理功能是促进葡萄糖的摄取和代谢.生物大分子的功能及其表现的基础是分子结构及参与功能表现的诸多分子, 如受体、信号分子等等.     

Discrepancy between GLUT4 translocation and glucose uptake after ischemia

Objective: Low-flow ischemia results in glucose transporter translocation and in increased glucose uptake. After total ischemia in rat heart, we found no increase in glucose uptake. Here we test the hypothesis that total ischemia is associated with decreased activation of GLUT4 despite translocation. Methods: Isolated working hearts (n=70, Sprague–Dawley rats) were perfused for 70 min at physiological workload with Krebs–Henseleit buffer containing [2-³H]glucose (5 mmol/l, 0.05 μCi/ml) with either oleate (0.4 mmol/l, 1%BSA) or pyruvate (5 mmol/l, 1%BSA). After 20 min, hearts were subjected to 15 min of total ischemia followed by 35 min of reperfusion. We measured glucose uptake and intracellular free glucose (IFG) using [2-³H]glucose and [¹⁴C]sucrose, and determined the distribution of GLUT4 by colocalization immunofluorescence with Na–K ATP-ase. Results: Cardiac power was 10.1 ± 0.90 mW before ischemia and did not differ between groups. Recovery was the same in both groups (55.7 ± 24.8$%). Glucose uptake did not differ between groups before ischemia, and did not increase during reperfusion. Despite evidence of GLUT4 translocation after reperfusion in both groups, IFG did not increase compared with before ischemia. Conclusion: We conclude that there is a discrepancy between glucose transporter availability and glucose uptake after ischemia, which may be due to inhibition of GLUT4 in the plasma membrane. (Mol Cell Biochem 278: 129–137, 2005)     

胰岛素信号转导通路和衰老研究进展

衰老是生物学中一个基本的、尚未解决的问题。过去十几年在无脊椎动物方面的研究表明,胰岛素/胰岛素样生长因子信号通路发生改变可以增加寿命和延迟衰老。在酵母、线虫、果蝇和小鼠等方面的研究已经勾画出了这个神秘问题的大致轮廓。     

Mechanisms of transmembrane signalling in human T cell activation

Several monoclonal antibodies directed against a number of T cell surface molecules are used to elucidate the role of these molecules (cell surface molecules) in T cell activation. The activation of T cells via these molecules are both antigen-dependent (CD3/TcR complex) and antigen-independent. Irrespective of their antigen-dependency, these monoclonal antibodies activate T cells by a classical signal transduction pathway, in which the binding of monoclonal antibodies to their cell surface receptors leads to activation of phospholipase C resulting in the the depolarization of plasma membrane, hydrolysis of IP2 and IP3 and DAG, the second messengers. IP3 leads to mobilization of intracellular calcium to contribute to an increase in [Ca⁺⁺]_i, whereas DAG causes activation and translocation of PKC and an increasing apparent affinity for Ca⁺⁺. The role of IN in the mobilization of intracellular calcium is emerging. In addition, influx of extracellular calcium also contributes to increase in [Ca^–+];. The increase in [Ca⁺⁺]; following activation via some T cell surface antigen is predominantly due to intracellular mobilization of Ca^–+ (e.g. CD3/TcR complex), whereas activation via other T cell surface antigen, the increase in [Ca^+–]_i is almost entirely due to an influx of extracellular calcium (e.g. CD5 antigen). All these molecules activate autocrine system of T cell growth, namely IL-2 production, IL-2 receptor expression and T cell proliferation.     

Selection and growth regulation of genetically modified cells with hapten‐specific antibody/receptor tyrosine kinase chimera

Although receptor tyrosine kinases (RTKs) play a pivotal role in the development and maintaining the homeostasis of the body, overexpression or mutation of RTKs often induces tumorigenesis or metastasis. To mimic the function of RTKs, we developed two fusion receptors consisting of anti‐fluorescein antibody single‐chain Fv, extracellular D2 domain of erythropoietin receptor and transmembrane/intracellular domains of epidermal growth factor receptor or c‐fms based on previously constructed antibody/cytokine receptor chimeras. The expression of these chimeric receptors in the hematopoietic cell line Ba/F3 and non‐hematopoietic cell line NIH/3T3 resulted in the activation of receptors themselves, downstream signaling molecules and cell proliferation in response to fluorescein‐conjugated BSA, leading to selective expansion of transduced cells up to almost 100%. These results indicate that the cognate antigen could activate the chimeric receptors even though the wild‐type extracellular domains were switched to the antibody fragment. This is the first study to show that our antigen‐mediated genetically modified cell amplification (AMEGA) system could be applied to non‐hematopoietic cells by utilizing antibody/RTK chimeras. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009     

胰岛素受体介导的信号传递

就胰岛素与其受体结合后, 信号传递的过程及参与信号传递的细胞内信号分子进行了综述.胰岛素作为一种重要激素,参与机体的新陈代谢, 调节细胞的生长分化.其发挥生理功能的第一步是与靶细胞膜上的受体相结合, 激活胰岛素受体的酪氨酸激酶活性, 随之磷酸化细胞内的信号分子, 从而使胰岛素的刺激信号转化为细胞反应.     

Networking with mitogen-activated protein kinases

Mitogen activated protein (MAP) kinases and their target ribosomal protein S6 (RSK) kinases have been recognized as shared components in the intracellular signaling pathways of many diverse cytokines. Recent studies have extended this protein kinase cascade by identifying the major activator of vertebrate MAP kinases as a serine/threonine/tyrosine-protein kinase called MEK, which is related to yeast mating factor-regulated protein kinases encoded by the STE7 and byr1 genes. MEK, in turn, may be activated following its phosphorylation on serine by either of the kinases encoded by proto-oncogenesraf1 ormos, as well as by p78 ^mekk , which is related to the yeast STE11 and byr2 gene products. Isoforms of all of these protein kinases may specifically combine to assemble distinct modules for intracellular signal transmission. However, the fundamental architecture of these protein kinase cascades has been highly conserved during eukaryotic evolution.     

胰岛素的促生长作用

除了经典的代谢调节作用之外,胰岛素还具有重要的促生长作用：在体外胰岛素能够刺激众多细胞的增殖与分化,一些实验证明胰岛素在体内可能也是一种重要的生长调节因子.胰岛素的促生长作用通过细胞表面的胰岛素受体介导,但在较高的胰岛素浓度下也可以通过类胰岛素生长因子Ⅰ(IGF-Ⅰ)受体进行,在不同细胞体系中可能会有所不同.受体后的信号转导经过了一系列磷酸化和去磷酸化等途径,其中有胰岛素受体底物1(IRS-1)、Shc蛋白、Ras蛋白以及磷酸肌醇3激酶(PI3-K)等的参与.在胰岛素的分子表面很可能存在一些区域或位点,对其促生长作用有着更大的贡献,通过对一些高促生长活性的胰岛素类似物的研究已揭示出一些初步的证据.