Mechanisms of synaptic depression triggered by metabotropic glutamate receptors

Glutamate, by activation of metabotropic receptors (mGluRs), can lead to a reduction of synaptic efficacy at many synapses. These forms of synaptic plasticity are referred to as long-term depression (mGluR-LTD). We will distinguish between mGluR-LTD induced by pre- or postsynaptic receptors and mGluR-LTD induced by the locus of the expression mechanism of the synaptic depression. We will also review recent evidence that mGluR-mediated responses themselves are subject to depression, which may constitute a form of metaplasticity. Received 13 May 2008; received after revision 07 July 2008; accepted 11 July 2008     

Molecular and structural effects of inverse agonistic mutations on signaling of the thyrotropin receptor – a basally active GPCR

Several mutations that decrease the basal signaling activity of G-protein coupled receptors (GPCRs) with pathogenic implications are known. Here we study the molecular mechanisms responsible for this phenotype and investigate how basal and further activated receptor conformations are interrelated. In the basally active thyroid stimulating hormone receptor (TSHR) we combined spatially-distant mutations with opposing effects on basal activity in double-mutations and characterized mutant basal and TSH induced signaling. Mutations lowering basal activity always have a suppressive influence on TSH induced signaling and on constitutively activating mutations (CAMs). Our results suggest that the conformation of a basally ‘silenced’ GPCR might impair its intrinsic capacity for signaling compared to the wild-type. Striking differences in conformation and intramolecular interactions between TSHR models built using the crystal structures of inactive rhodopsin and partially active opsin help illuminate the molecular details underlying mutations decreasing basal activity. G. Kleinau, H. Jaeschke: These two authors contributed equally to this work. Received 31 July 2008; received after revision 12 September 2008; accepted 19 September 2008     

The innate immunity of the central nervous system in chronic pain: The role of Toll-like receptors

Toll-like receptors (TLRs) are a family of pattern recognition receptors that mediate innate immune responses to stimuli from pathogens or endogenous signals. Under various pathological conditions, the central nervous system (CNS) mounts a well-organized innate immune response, in which glial cells, in particular microglia, are activated. Further, the innate immune system has emerged as a promising target for therapeutic control of development and persistence of chronic pain. Especially, microglial cells respond to peripheral and central infection, injury, and other stressor signals arriving at the CNS and initiate a CNS immune activation that might contribute to chronic pain facilitation. In the orchestration of this limited immune reaction, TLRs on microglia appear to be most relevant in triggering and tailoring microglial activation, which might be a driving force of chronic pain. New therapeutic approaches targeting the CNS innate immune system may achieve the essential pharmacological control of chronic pain. Received 21 November 2006; received after revision 8 January 2007; accepted 7 February 2007     

Survivin在子宫腺肌病中的表达及与VEGF相关性研究

目的探讨凋亡抑制基因Survivin在子宫腺肌病的表达及其与VEGF的相关性。方法应用免疫组织化学S—P法,检测50例子宫腺肌病异位及在位内膜组织中Survivin、VEGF蛋白的表达,并与正常在位子宫内膜组织30例进行对照。结果子宫腺肌病异位内膜组织中Survivin蛋白阳性表达率为80％,明显高于正常内膜及在位内膜组织的表达率16．67％、16％（P〈0．05）;子宫腺肌病异位内膜组织中VEGF蛋白阳性表达率为56％,明显高于正常内膜及在位内膜组织的表达率38％、20％（P〈0．05）;Survivin蛋白表达与VEGF蛋白呈正相关（P〈0．01）。结论Survivin可通过抑制异位内膜细胞凋亡,参与血管形成对子宫腺肌病的发生、发展起作用;Survivin与VEGF在子宫腺肌病的发生、发展中起协同作用。     

一种烟碱乙酰胆碱受体(nChRs)显像前体化合物的合成及标记

以 2 溴 3 吡啶酚和 (S) 2 氮杂环丁烷羧酸为起始物 ,合成了一种以 N (CH3 ) 3 为取代基团的前体化合物 :6 [-N(CH3 ) 3 + I- ] A 85 380 .用此前体化合物进行18F标记取代 ,制得了可用于nChRs受体PET显像的标记化合物 :6 [18F] A 85 380 .整个放射标记分离时间为 5 0～5 5min .其标记率不低于 38%～ 4 8% ,比活度可达 0 .74× 10 11Bq/ μmol.     

海参皂苷Echinoside A通过MMP-9信号通路抑制肿瘤转移

从富含海参皂苷的革皮氏海参中分离纯化出Echinoside A（EA）,并研究了其抗肿瘤细胞转移活性及其作用机制。通过MTT法检测了EA对肿瘤细胞（HepG2）和人脐静脉内皮细胞生长的影响;采用细胞黏附实验、划痕愈合实验和Transwell小室侵袭模型研究了EA对肿瘤细胞黏附、迁移和侵袭能力的影响;采用体外小管形成实验...     

内皮素对心脏功能的影响

内皮素(Endothelin,ET)是由血管内皮细胞产生的具有强烈缩血管作用的血管活性肽.大量实验表明,内皮素对心脏具有广泛的影响,使冠状血管收缩,对心脏产生正性肌力作用,通过内皮素受体参与神经体液因素对心肌细胞的调节作用.     

VEGF与ILK在SACC中的表达及相关性研究

目的观察血管内皮生长因子(Vascular endothelial growth factor,VEGF)与整合素连接激酶(Integrin-linked kinase,ILK)在涎腺腺样囊性癌(Salivary adenoid cystic carcinoma,SACC)中的定位及表达,探讨VEGF与ILK在SACC中的作用,揭示SACC的发病机制.方法对30例SACC存档蜡块行免疫组化分析,观察VEGF与ILK在SACC中的表达分布情况.利用SPSS 13.0统计软件分析VEGF与ILK的差异性及相关性.结果在SACC中,VEGF阳性率为83.33%,ILK阳性率为76.67%;VEGF实验组与对照组比较,P0.05,ILK实验组与对照组比较,P0.05;VEGF与ILK在SACC中的表达存在正相关,r=0.388.结论在SACC的发生发展过程中,血管生成是其发生的重要步骤,血管的生长速率是其侵袭和转移的条件.VEGF与ILK在血管的生成过程中起着重要的作用,VEGF与ILK在SACC中的表达存在正性相关,它们共同作用于SACC的血管生成,影响SACC血管生长的速率.     

结肠癌患者血清中IL-8和VEGF的检测及临床意义

目的探讨白介素-8（IL-8）和血管内皮生长因子（VEGF）血清水平与结肠癌的关系．方法选择结肠癌住院患者64例,所有病例均经病理检查确诊．用ELISA法测定结肠癌患者术前、术后与健康者血清中IL-8和VEGF含量,采用方差分析进行组间两两比较．结果结肠癌患者血清IL-8和VEGF含量明显高于正常对照组（P〈0．05）,DukesC,D期结肠癌患者血清IL-8和VEGF含量明显高于A,B期（P〈0．05）;肿瘤根治术后血清IL-8和VEGF含量较术前明显降低（P〈0．05）,但仍高于正常对照组（P〈0．05）．结论检测血清IL-8和VEGF含量对于结肠癌病情估计和预后判断有重要意义．