单核细胞趋化蛋白-1与恶性胸腔积液

单核细胞趋化蛋白-1可促进癌细胞生长、转移及逃避机体免疫破坏,诱导肿瘤新生血管形成,增加血管通透性和参与肿瘤相关炎症反应.本文从恶性胸腔积液的发病机制着手,重点阐述单核细胞趋化蛋白-1在恶性胸腔积液发生、发展中的作用.     

脂质过氧化诱导培养的内皮细胞表达单核细胞趋化蛋白-1

在人脐静脉和牛主动脉内皮细胞培养基中加入联胺，引发其脂质过氧化损伤，观察能否诱导内皮细胞表述单核细胞起化蛋白河。用斑点杂交法检测内皮细胞暴露于联胺后其单核细胞趋化蛋白-1mRNA的表达，杂交用的探针为了r32P5’末端标记的寡核苷酸探针。同时，用酶联免疫反应检测内皮细胞暴露于联胺后．其条件培养基中的单核细胞趋化蛋白-1蛋白含量。斑点杂交显示．培养的内皮细胞可表达单核细胞趋化蛋白-1mRNA，暴露于联胺后．其单核细胞趋化蛋白-1mRNA表达水平明显升高。而且，单核细胞趋化蛋白-1mRNA表达水平与联胺的作用时间和浓度均呈正相关。酶联免疫反应显示，各组条件培养基中的单核细胞趋化蛋白-1蛋白含量亦与联胺作用的时间和浓度呈正相关。提示内皮细胞的脂质过氧化损伤可诱导其产生单核细胞起化蛋白-1增加，在动脉粥样硬化发生过程中单核细胞的聚集可能起重要作用。     

氧化型高密度脂蛋白对人单核细胞株THP-1细胞迁移及单核细胞趋化蛋白1含量的影响

为研究氧化型高密度脂蛋白对单核细胞的趋化作用及单核细胞趋化蛋白 1含量的影响 ,进一步探讨氧化型高密度脂蛋白的致动脉粥样硬化机制 ,以一次性密度梯度超速离心法分离人血浆高密度脂蛋白 ,硫酸铜介导法进行氧化修饰 ,单核细胞为培养的人单核细胞株THP 1细胞 ,趋化实验采用改良Boyden趋化室 ,酶联免疫吸附检测法测定单核细胞趋化蛋白 1的含量。结果显示 ,氧化型高密度脂蛋白对THP 1细胞具有明显的趋化作用 ,其蛋白质浓度在 5 0和 10 0mg L时进入膜内的细胞数分别是对照组的 2倍 (P <0 .0 5 )和 3倍 (P <0 .0 1) ;雌二醇可部分抑制氧化型高密度脂蛋白对THP 1细胞的趋化作用。氧化型高密度脂蛋白可促进THP 1细胞单核细胞趋化蛋白 1的释放 ,氧化型高密度脂蛋白组单核细胞趋化蛋白 1的水平 ,约为对照组的 2倍 (P <0 .0 1) ;雌二醇可部分抑制氧化型高密度脂蛋白对THP 1细胞单核细胞趋化蛋白 1释放的促进作用。以上提示 ,氧化型高密度脂蛋白还可能通过促进循环血中单核细胞向血管内膜层迁移和聚集以及单核细胞趋化蛋白 1的释放而促进动脉粥样硬化的发生 ,雌二醇对其具有一定的保护作用     

睾酮通过芳香化酶途径抑制人血管内皮细胞单核细胞趋化蛋白1的基因表达

目的 探讨睾酮对脐静脉内皮细胞生成单核细胞趋化蛋白1的影响与机制,分析睾酮与内皮细胞功能及动脉粥样硬化的关系.方法 脂多糖刺激体外培养的脐静脉内皮细胞,培养液中分别加入不同浓度睾酮(3×10-10、3×10-9、3×10-8、3×10-6 mol/L和3×10-4 mol/L),ELISA实验方法检测细胞上清液单核细胞趋化蛋白1蛋白含量,RT-PCR方法检测单核细胞趋化蛋白1 mRNA相对水平.培养液中加入雄激素受体拮抗剂或芳香化酶抑制剂,重复上述实验.结果 与空白对照组(374.16±10.2)比较,3×10-10 mol/L睾酮组上清液单核细胞趋化蛋白1蛋白含量明显增}Jn(424.50±11.3,P＜0.05),随着睾酮浓度增加,单核细胞趋化蛋白1逐渐减少,3×10-5 mol/L组差异具有统计学意义(292.29±12.6,P＜0.01).与对照组比较,3×10-9,3×10-6,3×10-5 mol/L组单核细胞趋化蛋白1mRNA水平明显降低.雄激素受体拮抗剂可逆转3×10-10mol/L睾酮对单核细胞趋化蛋白1对蛋白生成的影响,芳香化酶抑制剂可削弱睾酮对内皮细胞单核细胞趋化蛋白1基因表达与蛋白合成的抑制作用.结论 睾酮浓度降低,可促进血管内皮细胞发生炎症反应;睾酮达到生理浓度抑制内皮细胞发生炎症反应,这种作用是睾酮通过细胞内芳香化酶转化为雌激素实现的.     

单核细胞趋化蛋白-1与中枢神经系统疾病

单核细胞趋化蛋白1(MCP1)是趋化因子CC类亚家族成员之一,可趋化和激活单核细胞、T淋巴细胞等免疫细胞,促进多种细胞因子和炎症介质分泌,参与脑缺血再灌注损伤、创伤性脑损伤、实验性自身免疫性脑脊髓炎、AIDS脑病和中枢神经系统肿瘤等疾病的病理生理学过程。深入研究MCP1在中枢神经系统疾病中的作用机制,有可能为这些疾病的治疗找到一条新的途径。     

单核细胞趋化蛋白-1及受体在血管紧张素Ⅱ诱导的血管病变中的作用

在血管紧张素Ⅱ诱导的血管病变中,单核细胞趋化蛋白-1是最重要的化学趋化因子之一。血管紧张素Ⅱ通过一系列分子途径诱导单核细胞趋化蛋白-1的产生,并与其受体CCR2结合,进而引起或加速一系列血管疾病的进程。现就单核细胞趋化蛋白-1及受体CCR2在血管病变中的作用及血管紧张素Ⅱ诱导单核细胞趋化蛋白-1表达的分子途径作一综述。     

单核细胞趋化蛋白-1与中枢神经系统疾病

单核细胞趋化蛋白-1（MCP-1）是趋化因子CC类亚家族成员之一,可趋化和激活单核细胞、T淋巴细胞等免疫细胞,促进多种细胞因子和炎症介质分泌,参与脑缺血再灌注损伤、创伤性脑损伤、实验性自身免疫性脑脊髓炎、AIDS脑病和中枢神经系统肿瘤等疾病的病理生理学过程.深入研究MCP-1在中枢神经系统疾病中的作用机制,有可能为这些疾病的治疗找到一条新的途径.     

单核细胞趋化蛋白-1与缺血性卒中

炎症反应在缺血性卒中的发生和发展过程中起着重要作用.单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)是趋化因子CC类哑家族成员之一,可趋化和激活单核细胞、T细胞等多种细胞,促进细胞因子表达,参与缺血性脑损伤的发生.文章对MCP-1与缺血性卒中相关的研究进展做了综述.     

单核细胞趋化蛋白-1与肺部疾病关系的研究进展

<正>单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)是一种具有趋化效应的细胞因子,因氨基酸序列N端最早出现的两个半胱氨酸排列相邻而属于趋化因子CC亚家族,主要趋化单核/巨噬细胞、淋巴细胞等炎性细胞向病变部位聚集并被激活产生各种细胞因子,导致炎症产生与发展。主要由巨噬细胞、内皮细胞、单核细胞、树突细胞、上皮细胞等分泌,在促炎反应、血管重塑、肿瘤形成和转移、组织     

脱氢表雄酮对氧化型低密度脂蛋白诱导的平滑肌细胞单核细胞趋化蛋白1表达的影响及其机制

目的观察脱氢表雄酮对氧化型低密度脂蛋白诱导的血管平滑肌细胞分泌单核细胞趋化蛋白1的影响,并探讨其作用机制是否与细胞色素P450芳香酶的催化作用有关。方法使用脂质体转染法将含有细胞色素P450芳香酶基因的质粒和空白对照质粒分别转染至体外培养的血管平滑肌细胞,24h后给予氧化型低密度脂蛋白诱导及脱氢表雄酮刺激,采用逆转录聚合酶链反应、实时荧光定量聚合酶链反应及酶联免疫吸附法检测转染后各组细胞单核细胞趋化蛋白1的基因和蛋白表达水平。结果与氧化型低密度脂蛋白刺激组比较,给予氧化型低密度脂蛋白和脱氢表雄酮后单核细胞趋化蛋白1的分泌明显降低(P<0.05)。转染含有细胞色素P450芳香酶基因的质粒组和空白对照质粒组单核细胞趋化蛋白1的分泌差别不明显(P>0.05)。结论脱氢表雄酮能抑制氧化型低密度脂蛋白诱导的血管平滑肌细胞单核细胞趋化蛋白1的分泌升高,可能是其抗动脉粥样硬化的机制之一。而这一过程可能并不通过转化为雌雄激素而发挥,也许与其本身的生物学活性有关。     

Tau protein and beta protein

The main pathological features of Alzheimer's disease are Alzheimer neurofibrillary tangles and senile plaques. Recent biochemical research revealed that tangles are composed of tau protein and ubiquitin and amyloid in senile plaques is composed of beta protein which is a fragment of the membrane receptor protein. Although fraction, other data suggest that whole molecules become abnormal and aggregate into PHF. On the other hand, beta protein is a small cleavage product of the precursor protein. It is not concluded yet whether abnormal precursor proteins exist or not. Recent research in this field is reviewed.     

Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases caused by the conversion of prion protein (PrP^C) into an infectious isoform (PrP^Sc). How this event leads to pathology is not fully understood. Here we demonstrate that protein synthesis in neurons is enhanced via PrP^C interaction with stress-inducible protein 1 (STI1). We also show that neuroprotection and neuritogenesis mediated by PrP^C–STI1 engagement are dependent upon the increased protein synthesis mediated by PI3K-mTOR signaling. Strikingly, the translational stimulation mediated by PrP^C–STI1 binding is corrupted in neuronal cell lines persistently infected with PrP^Sc, as well as in primary cultured hippocampal neurons acutely exposed to PrP^Sc. Consistent with this, high levels of eukaryotic translation initiation factor 2α (eIF2α) phosphorylation were found in PrP^Sc-infected cells and in neurons acutely exposed to PrP^Sc. These data indicate that modulation of protein synthesis is critical for PrP^C–STI1 neurotrophic functions, and point to the impairment of this process during PrP^Sc infection as a possible contributor to neurodegeneration.     

丙型肝炎病毒核心蛋白结合蛋白

0 引言1989年应用分子生物学技术发现了丙型肝炎病毒(hepatitisCvirus,HCV),并证实可导致肝脏慢性疾病,是输血后肝炎的主要病因.全世界有1.7亿人感染 HCV,面临肝硬化和肝细胞癌的威胁.随着基因组测序工作的完成,随后就是研究基因的功能,其中基因表达蛋白质的功能的研究尤为重要,因为基因是通过蛋白质起作用的.蛋白质与蛋白质之间的相互作用揭示了蛋白质功能     

乙型肝炎病毒X蛋白结合蛋白

随着人和各种生物的基因和基因组测序的完成,生物学和医学正处在一深刻变革的时代.基因组学(genomics)是指对人和其他生物类型基因组结构与功能的分析.基因组学可以分为结构基因组学(structural genomics)和功能基因组学(functional genomics),功能基因组学是指应用整体的研究技术阐明这些基因和蛋白的生物学功能.各种生物系统是一个复杂的系统,基因组中基因的序列是一个庞大的数据库,因此,需要发展一些强大的分析技术,代替传统的分析技术,对这些基因和蛋白质的功能进行研究.基因是 DNA 中的一些具有功能的单位,在遗传信息的流向中,首先转录生成中间产物 RNA,然后再翻译成具有生物学功能的蛋白质.蛋白质是执行生命活动的基本成分.作为基因的一段 DNA,一般包括调节基因序列和编码基因序列.功能基因组学的主要任务就是阐明这些基因及其编码产物的结构与功能、表达与调控.第一,人类不同个体之间的基因序列之间的区别;第二,人和人之间决定疾病状态和疾病的易感性基因;第三,引起疾病的各种病原体,还有包括大肠杆菌、酵母、果蝇、线虫、人等合成的每一种蛋白的功能;第四,这些不同的蛋白协同完成生命的活动的机制;第五,在特定的细胞类型和特定的时间内,并不是所有的基因都具有表达活性,决定选择性的表达和活动机制;第六,在多细胞生物中,不同的基因表达是形成不同的细胞和组织的机制.中国人民解放军第302医院传染病研究所基因治疗研究中心,在成军博士、教授、主任医师、博士生导师的领导下,应用功能基因组学的研究技术,研究乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)感染之后,肝细胞基因组表达调节的改变及机制.这是肝炎病毒感染肝细胞之后,引起病毒性肝炎、肝硬化、肝细胞癌的发病机制.基因组计划完成之后,提供能了大量的人和其他生物类型的基因序列,即将完成了结构基因组学的任务,但是,功能基因组学的任务还有许多的工作要做.利用抑制性消减杂交(SSH)、基因芯片技术,酵母单杂交技术、酵母双杂交技术、噬菌体展示技术等对于调节肝炎病毒基因的复制和表达,肝炎病毒蛋白结合蛋白,肝炎病毒蛋白表达对于肝细胞基因表达谱的影响,从而为揭示肝炎病毒感染肝细胞的致病机制的研究,开辟新的研究方向.     

Robust protein protein interactions in crowded cellular environments

The capacity of proteins to interact specifically with one another underlies our conceptual understanding of how living systems function. Systems-level study of specificity in protein-protein interactions is complicated by the fact that the cellular environment is crowded and heterogeneous; interaction pairs may exist at low relative concentrations and thus be presented with many more opportunities for promiscuous interactions compared with specific interaction possibilities. Here we address these questions by using a simple computational model that includes specifically designed interacting model proteins immersed in a mixture containing hundreds of different unrelated ones; all of them undergo simulated diffusion and interaction. We find that specific complexes are quite robust to interference from promiscuous interaction partners only in the range of temperatures T(design) > T > T(rand). At T > T(design), specific complexes become unstable, whereas at T < T(rand), formation of specific complexes is suppressed by promiscuous interactions. Specific interactions can form only if T(design) > T(rand). This condition requires an energy gap between binding energy in a specific complex and set of binding energies between randomly associating proteins, providing a general physical constraint on evolutionary selection or design of specific interacting protein interfaces. This work has implications for our understanding of how the protein repertoire functions and evolves within the context of cellular systems.     

Identifying hydrophobic protein patches to inform protein interaction interfaces

Interactions between proteins lie at the heart of numerous biological processes and are essential for the proper functioning of the cell. Although the importance of hydrophobic residues in driving protein interactions is universally accepted, a characterization of protein hydrophobicity, which informs its interactions, has remained elusive. The challenge lies in capturing the collective response of the protein hydration waters to the nanoscale chemical and topographical protein patterns, which determine protein hydrophobicity. To address this challenge, here, we employ specialized molecular simulations wherein water molecules are systematically displaced from the protein hydration shell; by identifying protein regions that relinquish their waters more readily than others, we are then able to uncover the most hydrophobic protein patches. Surprisingly, such patches contain a large fraction of polar/charged atoms and have chemical compositions that are similar to the more hydrophilic protein patches. Importantly, we also find a striking correspondence between the most hydrophobic protein patches and regions that mediate protein interactions. Our work thus establishes a computational framework for characterizing the emergent hydrophobicity of amphiphilic solutes, such as proteins, which display nanoscale heterogeneity, and for uncovering their interaction interfaces.

Protein–protein interactions play a crucial role in numerous biological processes, ranging from signal transduction and immune response to protein aggregation and phase behavior (1–3). Consequently, being able to understand, predict, and modulate protein interactions has important implications for understanding cellular processes and mitigating the progression of disease (4, 5). A necessary first step toward this ambitious goal is uncovering the interfaces through which proteins interact (6–8). In principle, identifying hydrophobic protein regions, which interact weakly with water, should be a promising strategy for uncovering protein interaction interfaces (9, 10). Indeed, the release of weakly interacting hydration waters from hydrophobic regions can drive protein interactions, as well as other aqueous assemblies (11–13). However, even when the structure of a protein is available at atomistic resolution, it is challenging to identify its hydrophobic patches because they are not uniformly nonpolar, but display variations in polarity and charge at the nanoscale. Moreover, the emergent hydrophobicity of a protein patch stems from the collective response of protein hydration waters to the nanoscale chemical and topographical patterns displayed by the patch (14–20) and cannot be captured by simply counting the number of nonpolar groups in the patch, or even through more involved additive approaches, such as hydropathy scales or surface-area models (21–28).To address this challenge, we build upon seminal theoretical advances and molecular simulation studies, which have shown that near a hydrophobic surface, it is easier to disrupt surface–water interactions and form interfacial cavities (29–34). To uncover protein regions that have the weakest interactions with water, here, we employ specialized molecular simulations, wherein protein–water interactions are disrupted by systematically displacing water molecules from the protein hydration shell (35–37). By identifying the protein patches that nucleate cavities most readily in our simulations, we are then able to uncover the most hydrophobic protein regions. Interestingly, we find that both hydrophobic and hydrophilic protein patches are highly heterogeneous and contain comparable numbers of nonpolar and polar atoms. Our results thus highlight the nontrivial relationship between the chemical composition of protein patches and their emergent hydrophobicity (24–26), and further emphasize the importance of accounting for the collective solvent response in characterizing protein hydrophobicity (16). We then interrogate whether the most hydrophobic protein patches, which nucleate cavities readily, are also likely to mediate protein interactions. Across five proteins that participate in either homodimer or heterodimer formation, we find that roughly 60 to 70% of interfacial contacts and only about 10 to 20% of noncontacts nucleate cavities. Our work thus provides a versatile computational framework for characterizing hydrophobicity and uncovering interaction interfaces of not just proteins, but also of other complex amphiphilic solutes, such as cavitands, dendrimers, and patchy nanoparticles (38–41).     

Gene and protein sequences of adenovirus protein VII, a hybrid basic chromosomal protein.

The sequences of both the gene and the corresponding protein of adenovirus major core protein VII have been determined. The precise location of this gene is between 43.37 and 44.90 map coordinates on the viral genome. Protein VII is 173 residues long and has a molecular weight of 19,258. Detailed analysis of its sequence has revealed four basic domains separated by several predicted alpha helices. It is proposed that intrachain folding of protein VII is driven by hydrophobic interactions of the alpha helices, leaving the basic domains of the protein to interact with DNA phosphates. Protein monomers may further associate with each other in the formation of hexameric nucleosome-like particles. The displacement and replacement of protein VII during the viral infectious cycle in the host cell appears to mimic the biology of nucleoprotamine during the processes of spermatogenesis and fertilization. The presence of a protamine-like domain affirms a hybrid histone/protamine molecular structure for protein VII, although it may resemble the protamine in function.     

Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein

Haptoglobin-related protein (Hpr) is a primate-specific plasma protein associated with apolipoprotein L-I (apoL-I)-containing high-density lipoprotein (HDL) particles shown to be a part of the innate immune defense. Despite the assumption hitherto that Hpr does not bind to hemoglobin, the present study revealed that recombinant Hpr binds hemoglobin as efficiently as haptoglobin (Hp). However, in contrast to Hp, Hpr did not promote any high-affinity binding to the scavenger receptor CD163. Binding of hemoglobin to circulating native Hpr incorporated into the HDL fraction was indicated by hemoglobin-affinity precipitation of plasma Hpr together with apoL-I. In conclusion, plasma has 2 high-affinity hemoglobin-binding haptoglobins instead of one, but only Hp-hemoglobin complexes are efficiently recognized by CD163. Circulating Hpr-bound hemoglobin should therefore be taken into consideration when measuring "free" plasma hemoglobin. Furthermore, Hpr-bound hemoglobin might contribute to the biologic activity of the circulating apoL-I/Hpr-containing HDL particles.