环二鸟苷酸对细菌运动调控的研究进展

细菌中的第二信使环二鸟苷酸(c-di-GMP)对细菌的运动性有调节作用.c-di-GMP调控鞭毛的生物合成、菌毛形成和菌毛蛋白的组成,以及其他一些与运动相关的蛋白的合成.细菌的运动性与其毒力、致病性、粘附性、趋化性、生物膜组成等密切相关.在革兰氏阴性细菌中,关于c-di-GMP的信号通路的研究较为清晰,而在革兰氏阳性细菌中,关于该信号转导通路的研究较少.此外,有关c-di-GMP的信号通路的研究主要集中在病原菌.该文主要综述了一些常见病原菌中c-di-GMP对其运动性的调控机制,为研究其他细菌c-di-GMP信号通路提供思路.     

水杨酸信号转导及其在植物抵御生物胁迫中的作用

水杨酸(SA)是植物防卫反应的重要内源信号分子,在植物抵御生物性胁迫中发挥重要作用.近年来,SA信号转导研究取得了较大进展,确定了以NPR1为中心组分的信号转导途径.同时发现,SA介导的植物抗逆途径与其他信号转导途径间还存在着复杂的对话机制.文中介绍了生物胁迫诱导引起PR-1基因表达的SA信号转导途径中的重要组分及其可能的模式,以及SA与其他信号分子如茉莉酸(JA)、脱落酸(ABA)和一氧化氮(NO)等之间的互作关系,并对这一领域今后的研究进行了展望.     

WspR在大肠杆菌中的表达及其对c-di-GMP合成的影响

可得胶是土壤农杆菌ATCC31749分泌的一种胞外多糖,大多数细菌胞外多糖的合成受控于新近发现的第二信使环二鸟苷酸(c-di-GMP).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.研究表明从绿脓杆菌(P.aeruginosa)中得到的类趋化系统蛋白WspR具有GGDEF结构域,具有DGC活性.本实验将WspR转入大肠杆菌中得到了表达,并用颜色反应得到证实c-di-GMP在E.coli大量合成.为进一步研究ATCC31749中WspR的作用机制,促进可得胶的合成提供切实可行的依据.     

Fas/FlasL 系统与胆管癌的免疫逃逸

自1999年国外学者Que FG等发现Fas/FasL系统在胆管癌等恶性肿瘤的免疫赦免与逃逸过程中起重要作用以来,有关胆管癌Fas/FasL系统逃避免疫系统监视的机理及胆管癌治疗研究得到了蓬勃发展.本文就Fas/FasL系统介导细胞凋亡的信号转导机制、信号转导途径的调节和在诱导胆管癌免疫逃逸等方面进行了综述.     

双组分系统RaxH/RaxR与RavA/RavR的共进化关系

本研究对细菌中的两个双组分系统(RaxH/RaxR与RavA/RavR)之间及其自身两个蛋白之间是否具有共进化特征进行了分析,发现其存在高度的共进化关系,预示它们之间在信号传导中可能处于某一传导途径的不同节点.通过遗传分析发现,RaxH/RaxR在转录水平上调控ravA/ravR的表达,应位于RavA/RavR信号传递的上游.由于RaxH/RaxR可能感应和传导群体信号,而RavA/RavR又调控细胞第二信使c-di-GMP的代谢,所以此双组分级联系统可能在细菌群体行为中扮演重要的角色.     

LysM蛋白在植物免疫中的作用

溶解素基序（LysM）是在多种蛋白质中普遍存在的结构域.植物LysM蛋白能够感知几丁质及其寡糖等分子配体，从而启动植物对病原菌的免疫反应.在水稻、拟南芥等植物免疫应答过程中，LysM蛋白作为一种重要的模式识别受体，通过不同形式的寡聚化，激活多种类受体胞质激酶及其下游的MAPK（mitogen activated protein kinase）级联反应传递信号.同时，蛋白质可逆磷酸化和蛋白质降解途径可以负调节LysM蛋白介导的防御信号转导.文章综述了植物免疫过程中LysM蛋白介导的信号转导分子机制.     

E3泛素连接酶Pellino蛋白的研究进展

Pellino蛋白是近年来新发现的一类E3泛素连接酶,通过靶蛋白泛素化介导蛋白降解、蛋白与蛋白的相互作用、蛋白质细胞定位以及信号传导.目前研究表明Pellino蛋白在固有免疫细胞和获得性免疫细胞中具有重要调控作用,与炎症和自身免疫密切相关.本文总结了近年来Pellino蛋白的表达与活性调控、介导的信号转导途径以及在免疫...     

C-di-GMP signaling and implications for pathogenesis of Mycobacterium tuberculosis

C-di-GMP is a ubiquitous bacterial second messenger that regulates a wide range of bacterial physiological processes including biofilm formation, virulence, motility and cell differentiation. Here, we have summarized our current knowledge on the upstream signaling factors and downstream effectors of c-di-GMP in addition to the interaction between c-di-GMP and eukaryotic organisms. New discoveries in these areas have enriched our understanding of the diversity of c-di-GMP signaling pathways and provide important clues for us to explore the roles of c-di-GMP signaling in human pathogens such as Mycobacterium tuberculosis.     

系统素信号转导研究进展

系统素最初是指在番茄叶片中发现的与植物防卫反应相关的一种18个氨基酸的多肽信号,随着在茄科植物中其他相类似的多肽防卫信号的发现,现系统素被定义为茄科植物中具有调节防卫基因功能的一类多肽信号家族.近年来对系统素信号转导的研究取得了很大进展,不仅在系统素信号转导途径上,而且在系统素与其他信号转导途径的相互作用上均有了很大进展.文中介绍了系统素的信号转导途径以及系统素与其他信号转导途径,如与油菜素甾醇类激素(BRs)和紫外线-B(UV-B)信号转导途径之间的相互作用,并对这一领域的研究进行了展望.     

细菌运动及趋化信号转导网络的研究

细菌运动是其生存及致病的关键条件,其动力来源于运动马达,并受各种信号转导系统的控制.大肠杆菌(E.coli)及相关的沙门氏菌(Salmonella enterica)被普遍用来研究细菌运动.它们游动的动力来源于鞭毛马达驱动鞭毛的转动,并受趋化信号转导系统调控.本文综述了关于细菌鞭毛马达及趋化信号转导系统近年来的研究进展,并展望未来需发展或深入探索的重点和方向.     

The prokaryote messenger c-di-GMP triggers stalk cell differentiation in Dictyostelium

Cyclic di-(3′:5′)-guanosine monophosphate (c-di-GMP) is a major prokaryote signalling intermediate that is synthesized by diguanylate cyclases and triggers sessility and biofilm formation. We detected the first eukaryote diguanylate cyclases in all major groups of Dictyostelia. On food depletion, Dictyostelium discoideum amoebas collect into aggregates, which first transform into migrating slugs and then into sessile fruiting structures. These structures consist of a spherical spore mass that is supported by a column of stalk cells and a basal disk. A polyketide, DIF-1, which induces stalk-like cells in vitro, was isolated earlier. However, its role in vivo proved recently to be restricted to basal disk formation. Here we show that the Dictyostelium diguanylate cyclase, DgcA, produces c-di-GMP as the morphogen responsible for stalk cell differentiation. Dictyostelium discoideum DgcA synthesized c-di-GMP in a GTP-dependent manner and was expressed at the slug tip, which is the site of stalk cell differentiation. Disruption of the DgcA gene blocked the transition from slug migration to fructification and the expression of stalk genes. Fructification and stalk formation were restored by exposing DgcA-null slugs to wild-type secretion products or to c-di-GMP. Moreover, c-di-GMP, but not cyclic di-(3′:5′)-adenosine monophosphate, induced stalk gene expression in dilute cell monolayers. Apart from identifying the long-elusive stalk-inducing morphogen, our work also identifies a role for c-di-GMP in eukaryotes.     

Cytokinin signal transduction： Known simplicity and unknown complexity

Cytokinin plays a critical role in plant growth and development by regulating cell divisions and cell differentiation. Recent studies suggest that cytokinin signaling is presumably mediated by a two-component system analogous to those found in bacteria and fungi, which transduces an external signal via a phosphorelay from the plasma membrane-anchored receptors to downstream effectors and regulators. Moreover, cytokinin signaling is highly interactive with other pathways, and many components of the pathway appear to be functionally redundant. Proper address of these questions will be crucial for our further understanding on this important network.     

Aminoglycoside antibiotics induce bacterial biofilm formation

Biofilms are adherent aggregates of bacterial cells that form on biotic and abiotic surfaces, including human tissues. Biofilms resist antibiotic treatment and contribute to bacterial persistence in chronic infections. Hence, the elucidation of the mechanisms by which biofilms are formed may assist in the treatment of chronic infections, such as Pseudomonas aeruginosa in the airways of patients with cystic fibrosis. Here we show that subinhibitory concentrations of aminoglycoside antibiotics induce biofilm formation in P. aeruginosa and Escherichia coli. In P. aeruginosa, a gene, which we designated aminoglycoside response regulator (arr), was essential for this induction and contributed to biofilm-specific aminoglycoside resistance. The arr gene is predicted to encode an inner-membrane phosphodiesterase whose substrate is cyclic di-guanosine monophosphate (c-di-GMP)-a bacterial second messenger that regulates cell surface adhesiveness. We found that membranes from arr mutants had diminished c-di-GMP phosphodiesterase activity, and P. aeruginosa cells with a mutation changing a predicted catalytic residue of Arr were defective in their biofilm response to tobramycin. Furthermore, tobramycin-inducible biofilm formation was inhibited by exogenous GTP, which is known to inhibit c-di-GMP phosphodiesterase activity. Our results demonstrate that biofilm formation can be a specific, defensive reaction to the presence of antibiotics, and indicate that the molecular basis of this response includes alterations in the level of c-di-GMP.     

含葡聚糖颗粒物暴露致小鼠肺部GSNO还原酶活化的研究

动物实验和体外研究都已表明,空气中有机颗粒物可引起肺部炎症反应,该反应的显著特点为细胞因子表达上调和分泌增多.葡聚糖是霉菌和细菌代谢及裂解的产物,当颗粒物受到霉菌和细菌污染之后,就会含有葡聚糖.最近的研究表明,含葡聚糖颗粒物的暴露会影响鼻腔和肺部的功能,并伴随炎症反应.然而,含葡聚糖颗粒物的暴露对一氧化氮合酶(NOS)和亚硝基谷胱甘肽还原酶(GSNOR)的影响仍不太清楚.本研究旨在检测含葡聚糖颗粒物暴露对呼吸道中NO信号通路的影响.本实验力小鼠被分别暴露于20μL PBS(空白组),20μL浓度为25μg/20μL的OVA和20μL浓度为100μL/20μL的含葡聚糖颗粒物环境中,暴露持续12d.暴露结束后在肺组织匀浆中检测NOS和GSNOR的活性.同时测定肺组织中谷胱甘肽(GSH)浓度和SOD活性用以评估氧化应激水平.另外,检测肺组织中的IL–6浓度确定炎症反应的发生与否.结果显示,12天OVA和葡聚糖颗粒物暴露并未明显影响NOS活性、GSH含量、SOD活性和IL-6浓度.然而,含葡聚糖颗粒物12d的暴露却明显增加GSNOR的活性和表达.我们的研究结果表明,含葡聚糖颗粒物暴露会激活呼吸道中的GSNOR,但不激活NOS.由于GSNOR在NO信号通路中起着举足轻重的作用,我们的研究结果具有一定的临床重要性.     

Regulation of the arachidonic acid-stimulated respiratory burst in neutrophils by intracellular and extracellular calcium

The respiratory burst is an important physiological function of the neutrophils in killing the bacteria invading in human body. We used chemiluminescence method to measure the exogenous arachidonic acid-stimulated respiratory burst, and measured the cytosolic free calcium concentration in neutrophils by the fluorescence method. It was found that, on one hand, the arachidonic acid-stimulated respiratory burst was enhanced by elevating the cytosolic free calcium concentration in neutrophils with a potent endomembrane Ca2+-ATPase inhibitor, Thapsgargin; on the other hand, chelating the intracellular or extracellular calcium by EGTA or BAPTA inhibited the respiratory burst. Results showed that calcium plays an important regulatory role in the signaling pathway involved in the exogenous arachidonic acid-stimulated respiratory burst of neutrophils.     

Wnt/β-catenin信号途径在DDR和氧化应激中的作用

Wnt/β-catenin信号途径在调控基因表达与DNA损伤反应(DNA damage response,DDR)中具有重要作用.氧化应激是导致DNA损伤的主要原因,且可以影响Wnt信号.首先总结了Wnt/β-catenin信号途径和DDR,然后综述了Wnt/β-catenin信号途径在DDR和氧化应激中的作用及分子机制,以期为DNA修复缺陷性肿瘤提供更有效的治疗策略.