The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation

Atherosclerotic lesions form at distinct sites in the arterial tree, suggesting that hemodynamic forces influence the initiation of atherogenesis. If NF-kappaB plays a role in atherogenesis, then the activation of this signal transduction pathway in arterial endothelium should show topographic variation. The expression of NF-kappaB/IkappaB components and NF-kappaB activation was evaluated by specific antibody staining, en face confocal microscopy, and image analysis of endothelium in regions of mouse proximal aorta with high and low probability (HP and LP) for atherosclerotic lesion development. In control C57BL/6 mice, expression levels of p65, IkappaBalpha, and IkappaBbeta were 5- to 18-fold higher in the HP region, yet NF-kappaB was activated in a minority of endothelial cells. This suggested that NF-kappaB signal transduction was primed for activation in HP regions on encountering an activation stimulus. Lipopolysaccharide treatment or feeding low-density lipoprotein receptor knockout mice an atherogenic diet resulted in NF-kappaB activation and up-regulated expression of NF-kappaB-inducible genes predominantly in HP region endothelium. Preferential regional activation of endothelial NF-kappaB by systemic stimuli, including hypercholesterolemia, may contribute to the localization of atherosclerotic lesions at sites with high steady-state expression levels of NF-kappaB/IkappaB components.     

Notch信号通路与肺动脉高压

肺动脉高压( pulmonary hypertension,PH)时,参与肺血管重塑的内皮细胞、平滑肌细胞等存在不同程度的Notch家族基因表达上调.Notch信号转导通路在肺血管形成,血管平滑肌细胞及内皮细胞等增殖、分化、凋亡方面起重要调控作用.Notch信号转导通路参与PH形成和发展.这为PH的治疗提供了前景广阔的...     

Alterations in the cAMP signal transduction pathway in mouse lung tumorigenesis.

Alterations in the cAMP signal transduction pathway are associated with mouse lung neoplasia, cAMP effects are mediated by activating cAMP-dependent protein kinase isozymes, PKA I and PKA II. E9, a tumorigenic cell line, exhibited decreased PKA I levels compared to C10 cells, a nontumorigenic cell line of similar epithelial origin. Western immunoblots of PKA subunit proteins demonstrated low concentrations of both the catalytic (C) and regulatory (RI) PKA I subunits. Although RII (regulatory subunit of PKA II) concentrations were similar in both cell lines, RII from E9 cells was more highly phosphorylated than in C10 cells. RII phosphorylation status regulates cAMP activation of PKA II. Northern-blot analysis of mRNA content indicated diminished expression of both C and RI mRNA in E9 relative to C10 cells. Several endogenous PKA substrate proteins present in C10 cells were minimally phosphorylated by PKA in E9 cells. Forskolin, which raises cellular cAMP content, increased phosphorylation of a protein doublet in intact C10 cells, but not in E9 cells. Decreased PKA I expression and alterations in RII phosphorylation in lung neoplasia may contribute to anomalous regulation by cAMP, thereby diminishing cAMP-mediated growth inhibitory effects.     

生存素与肿瘤信号转导通路之间的关系

生存素是凋亡抑制蛋白家族新成员,是细胞增殖和凋亡调控界面间的结点分子.生存素基因表达的肿瘤特异性使其成为目前恶性肿瘤诊断和治疗的新靶点.肿瘤细胞发生与正常细胞的信号通路异常有关,信号转导通路的活化参与细胞癌变、增殖、凋亡等多种生物学效应.本文就肿瘤中信号转导对生存素基因的表达调控机制的研究进展作一综述.     

酪氨酸蛋白激酶/信号转导和转录激活因子信号转导途径与支气管哮喘

众多细胞因子通过调节Th2优势应答、IgE的类型转换、嗜酸粒细胞的募集和活化等生物学效应,在哮喘的发生发展中起着至关重要的作用。而越来越多的证据表明参与哮喘发病的多种细胞因子是通过活化Janus激酶／信号转导子和转录激活因子（JAK／STAT）途径转导信号,从而促进哮喘的发生发展的。新近研究发现JAK／STAT途径的异常在哮喘的发病机制中具有重要意义,从而提示JAK／STAT途径可望成为治疗哮喘的新靶点。     

肝纤维化的信号转导通路

肝纤维化是多种慢性肝病进展至肝硬化的中间过程,其特征为以胶原蛋白为主的细胞外基质(extracellular matrix,ECM)合成与降解失衡．现有的研究表明,肝星状细胞(hepatic stellate cells,HSC)是肝纤维化时过量ECM的主要来源,激活的HSC大量增殖,发生表型改变并分泌过多的ECM沉积于肝脏是肝纤维化形成的关键．这一复杂的病理过程是多条细胞信号传导通路和一系列细胞信息分子网络共同控制的结果,转化生长因子β(transforming growth factor beta,TGFβ)等细胞因子分别通过TGFβ- Smad通路、ROCK通路、MAPK(丝裂原激活的蛋白激酶,mitogen activatecl protein kinase)通路、Rho-、PI-3K通路等众多细胞信号通路网络交互影响,共同介导肝纤维化复杂的病理生理变化．现综述参与肝纤维化的主要信号转导通路及其可能的致肝纤维化机制．     

Role of the JNK signal transduction pathway in inflammatory bowel disease

The c-Jun NH2-terminal Kinase （JNK） pathway represents one sub-group of the mitogen-activated protein （MAP） kinases which plays an important role in various inflammatory diseases states, including inflammatory bowel disease （IBD）. Significant progress towards understanding the function of the JNK signaling pathway has been achieved during the past few years. Blockade of the JNK pathway with JNK inhibitors in animal models of IBD lead to resolution of intestinal inflammation. Current data suggest specific JNK inhibitors hold promise as novel therapies in IBD.     

Role of nitric oxide signal transduction pathway in regulation of vascular tone.

Nitric oxide signal transduction pathway has been detected in a number of cell types including vascular endothelial cells, smooth muscle cells, and noncholinergic nonadrenergic nerve endings. Nitric oxide synthase is a key enzyme which produces nitric oxide from L-arginine. Three different types of this enzyme have been described: constitutive soluble, inducible soluble, and constitutive particulate. Nitric oxide is a lipophilic molecule that can rapidly diffuse through biological membranes. It provides communication between endothelial and smooth muscle cells as well as between nerve endings and smooth muscle cells. Decreased production of nitric oxide may lead to vasospasm, whereas its overproduction may cause pathological vasodilatation. Understanding of the role of nitric oxide signal transduction pathway in regulation of vascular tone will facilitate design of better strategies for the prevention and treatment of vascular diseases.     

昆虫气味受体及其介导的嗅觉信号转导途径

减少媒介昆虫的叮咬是控制虫媒病的重要手段。然而,传统防制手段的弊端已逐渐暴露,因此,研制新型防制方法迫在眉睫。昆虫寻找宿主和吸血等行为在很大程度上是由其嗅觉系统控制的,因此,通过干扰昆虫嗅觉系统进行防制成为新的虫媒病控制手段。在昆虫通过嗅觉系统感受环境中众多气味分子的过程中,昆虫气味受体的作用尤为重要。本文就昆虫气味受体及其介导的嗅觉信号转导等方面取得的研究进展作一简要综述。     

Effects of thyroid hormone on the GH signal transduction pathway

Background/aimThe importance of thyroid hormone on growth and development in children is well recognized. In addition, linear growth is highly dependent on the response of peripheral tissues to growth hormone, a process known as GH sensitivity, but little is known about the possible effects of T4 on this process.MethodsWe determined the effect of stimulation with recombinant human GH (rhGH; 200 ng/mL) alone or in combination with two different concentrations of T4 (250 nM and 500 nM for 24 h) on JAK2 and STAT5 activation in skin fibroblast cultures obtained from prepubertal boys with normal height.ResultsJAK2 and STAT5 were activated under co-incubation with T4 (at both concentrations) and rhGH in the non-nuclear fraction of the fibroblasts. In addition, after 24 h of co-incubation with rhGH and T4 (500 nM), we observed an increase in phospho-STAT5 in the nuclear fraction, when compared to GH and T4 stimulation alone. This effect was not observed when the fibroblasts were co-incubated with GH and the lower concentration of T4 (250 nM).ConclusionCombined stimulation with GH and T4 at a concentration of 500 nM increases synergistically nuclear phospho-STAT5 in skin fibroblasts, which may amplify tissue sensitivity to GH. These findings may help to explain the effect of T4 administration on growth velocity in some children with idiopathic short stature.     

肝纤维化重要细胞因子的主要信号转导途径

多种细胞因子参与肝纤维化的发生、发展进程,它们通过多种信号转导途径,构成复杂的调节网络,对这一过程进行精密调控。随着生命科学的发展,多种细胞因子在其中发挥生物学作用的途径逐步被揭示,使我们对肝纤维化发生、发展机制的研究进一步深入。一、转化生长因子β(TGFβ)TGFβ超家族包含三类成员,其中与肝纤维化有关的主要是TGFβ家族和激活素。已知TGFβ1～3存在于人和哺乳动物中,其中TGFβ1在体细胞内所占比例最高(>90%),活性最强,是促使肝星状细胞(HSC)转化为肌成纤维细胞并分泌胶原纤维的细胞因子。TGFβ家族在所有类型的细胞…     

CaN-NFAT信号传导通路参与EPCs凋亡作用的研究

目的:研究钙调神经磷酸酶-活化T细胞核因子(CaN-NFAT)信号传导通路参与内皮祖细胞(EPCs)的凋亡过程。方法:采用密度梯度离心法分离外周血单个核细胞,贴壁培养获得EPCs。实验分为4组:空白对照组、苯肾上腺素(PE)组、环孢素A(CsA)组、CsA+PE组。采用TUNEL染色测定EPCs凋亡状况。逆转录聚合酶链反应法(RT-PCR)检测Bax、Bcl-2、Caspase-3及NFAT4的mRNA的转录水平。免疫荧光染色检测NFAT4亚细胞水平定位。结果:(1)EPCs凋亡检测:与空白对照组及PE组比较,CsA组和CsA+PE组EPCs凋亡数明显增加[(3.41±0.89)比(4.39±1.92)比(23.68±1.14)比(25.92±2.62),P<0.05];(2)与空白对照组和PE组比较,CsA组和CsA+PE组的Bcl-2mRNA水平、Bcl-2/Bax mRNA比值明显下降(P均<0.05),Caspase-3mRNA水平明显升高(P<0.05)。NFAT4mRNA水平:与空白对照组比较,PE组的明显升高(P<0.05),CsA组的明显下降(P<0.05);与PE组比较,CsA组和CsA+PE组的NFAT4mRNA水平均明显下降(P<0.05)。四组之间Bax mRNA水平均无显著差异;(3)与空白对照组比较,PE组NFAT4核转移率明显增加[(25.33±2.08)%比(95±2)%,P<0.05];与空白对照组及PE组比较,CsA组和CsA+PE组NFAT4核转移率[(8.00±2.65)%、(7.00±1.73)%]明显下降(P均<0.05)。结论:CaN-NFAT信号传导通路参与EPCs凋亡的调节作用。     

脂联素及其信号转导通路与高血压靶器官损害

高血压是一种常见而多发的心血管疾病,我国目前的高血压患者人数已超过1.6亿。高血压对机体的危害不仅是体循环的异常增高,更主要的是与之相伴的各种代谢异常及靶器官损害。血管、心脏、肾脏在高血压发展过程中将出现结构及功能的异常改变,从而又加重高血压形成恶性循环。脂联素(adiponectin)是脂肪细胞分泌的特殊蛋白质,通过调节代谢降低导致心血管疾病发生的多种危险因素,在高血压形成和发展过程中起重要作用。1脂联素及其信号转导通路与高血压1.1脂联素脂联素又叫Acrp30、AdipoQ、GBP28,是从脂肪细胞中分离出的一种结构上与补体因子C1…     

p38MAPK信号通路与内皮细胞激活

内皮细胞激活是内皮细胞损伤的始动因素,是引起各种不同程度的炎症反应和细胞凋亡的前提条件 ;丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK) 是哺乳动物细胞中重要的信号转导通路,其中 p38MAPK 通路在细胞应激、细胞生长、凋亡和炎症等多种生理和病理过程中起重要作用,越来越引起业界的广泛关注,本文就 p38MAPK 信号通路及其与内皮细胞激活的相关性做一综述,旨在进一步对内皮细胞损伤引发心血管疾病研究提供参考资料。