蛋白质组和蛋白质组学

(接第 9卷第 3期 )“蛋白质是我们理解细胞功能和疾病过程的核心 ,如果在蛋白质组学方面没有共同的努力 ,基因组学的成果将不会成为现实” .何为蛋白质组和蛋白质组学 .蛋白质组被定义为细胞 ,器官或组织型的蛋白质成分的总称 ,而蛋白质组学是研究这些成分在指定的时间或特定的环境条件下的表达 .蛋白质组学体现了基因组学的工作和它的动态过程 .蛋白质组学可分为表达蛋白质组学 ,研究蛋白质表达的整体变化 .细胞图谱蛋白质组学 ,通过蛋白质复合物的分离系统地研究蛋白质与蛋白质的相互作用 ,在生长 ,疾病和细胞及组织的死亡过程中机体变化…     

比较蛋白质组学研究与应用进展

蛋白质组学研究细胞内蛋白质组成及其活动规律是对不同时间和空间发挥功能的特定蛋白质群体的研究。通过比较分析不同条件蛋白质组的差异表达,着眼发现和鉴定出有差异的蛋白质或蛋白质群,即比较蛋白质组学。介绍比较蛋白质组学研究内容适用于比较蛋白质组学研究的相关技术及其在疾病研究中的应用进展。     

蛋白质组学在生殖医学中的应用

蛋白质组学是在人类基因组计划研究发展的基础上形成的新兴学科，蛋白质组主要是指一个基因组、一种生物或一种细膨组织所表达的全套蛋白质，它主要研究蛋白质的特性，包括蛋白质表达水平、氨基酸序列、翻译后加工和蛋白质的相互作用，在蛋白质水平上了解细胞的各种功能、生理生化及疾病的病理过程等。蛋白质组学集中于动态描述基因调节，对基因表达的蛋白质水平进行定量测定，鉴定疾病、药效对生命过程的影响，以及解释基因表达调控的机制。     

蛋白质组学在免疫学研究中的应用

蛋白质组学即应用一系列的技术手段,在基因组规模分析蛋白质表达情况,包括蛋白质表达丰度及其翻译后修饰等.正是因为蛋白质组学关注的对象是蛋白质(本质上催化和控制所有生物学过程的分子),蛋白质组学在众多组学分支中显得尤其引人注目.而对于高等动物的免疫系统而言,蛋白质除了发挥执行者的作用外,还具有调节免疫系统,清除病毒或微生物病原体感染,恶性肿瘤细胞的转化等重要功能.因此,蛋白质组学的方法是适于在分子水平进行免疫学研究的理想工具.本综述旨在介绍蛋白质组学在免疫学相关研究中的应用以及对免疫学领域热点问题的推动作用.     

蛋白质组(Proteome)和蛋白质组学(proteomics)(2)

90年代是基因组学研究的 10年而蛋白质组学则成为新世纪生命科学研究的重点 .蛋白质组学是在人类基因组计划研究发展的基础上形成的新兴学科 ,主要从整体水平研究细胞内蛋白质的组成 ,结构及其自身特有的活动规律 .蛋白质组学研究的最终目标是阐明生命细胞进行代谢、信号传导和调控网络的组织结构和动力学 ,并理解这些网络如何在病理中失去功能 ,又如何通过干预如药物和基因改变它们的功能 .“表达”“定量调节”蛋白质组学 ,是监控一个细胞或组织里大数量蛋白质的表达及定量观察在不同条件下表达方式如何改变 .使得可以识别疾病特异性蛋白…     

比较蛋白质组学在肝癌研究中的进展

随着人类全基因组计划的完成,生命科学的研究重点由基因转移到蛋白质上来,蛋白质组学(proteomics)应运而生.后者以蛋白质组为研究对象,以全面蛋白质的性质为研究基础,在蛋白质水平探讨对疾病机制、细胞模式和功能联系的科学[1].采用高分辨率的蛋白质分离手段,结合高通量的蛋白质鉴定技术,全面研究特定情况下蛋白质的表达谱.蛋白质具有动态性、多样性、时间性、空间性和特异性,其合成受多因素的调控.不同的组织细胞蛋白质的合成、表达的种类和数量有很大的差异,即使细胞发育的不同阶段,其蛋白质组的构成也在不断的变化.因此,蛋白质组是在空间和时间上动态变化着的整体,分析不同条件下蛋白质组的变化,发现和鉴定不同生理条件下蛋白质组的成分差异,是比较蛋白质组学的研究内容[2,3],即比较不同蛋白质组之间蛋白质在表达数量、表达水平和修饰状态上的差异.本文就比较蛋白质组学及其在肝细胞癌研究中的进展进行综述.     

“医学生物信息学专题杂志”专栏

基因组医学、染色体组和人类疾病基因 (7)细胞信号转导 (SignalTransduction)的研究是当前细胞生命活动研究的重要课题 .细胞信号转导蛋白质组学是功能蛋白质组学的重要组成部分 .系统地研究多条细胞信号转导通路中蛋白质及蛋白质间相互关系及其作用规律、细胞信号转导通路网络化 ,其作用模式、通路、功能机制、调控多样化 .细胞信号转导结构、功能、途径的异常在癌症、心血管疾病、糖尿病和大多数疾病中起重要作用 .对细胞信号转导机制的了解 ,已成为创新药物、防病治病的关键 .细胞信号转导不是一门单一学科 ,而是多种学科 ,如细胞学、生…     

蛋白质组学(Proteomics)——后基因组时代生命科学研究的重点之一

蛋白质组是在研究人类基因组计划 (HGP)完成后的后基因组计划中一个很重要的内容 .基因的主要功能是通过其表达产物蛋白质来完成的 ,而蛋白质亦具有相对独立的修饰、转运和相互间作用的能力、具有对外界因素反应的协调能力 ,有其独特的自身活动规律 ,蛋白质组学研究 ,才能更加贴近对生命现象和生命本质的了解 .蛋白质组学研究不仅对了解生命现象和生命本质有重要意义 ,在疾病诊断、药物基因组研究、药物靶点、药物筛选等方面均有广泛的应用前景 .蛋白质组学是研究细胞内全部蛋白质的表达方式和功能方式的一门学科 .通过蛋白质组学研究 ,从…     

蛋白质组学研究技术及其联合应用

蛋白质组学是研究细胞、组织和器官内所有蛋白质的组成及其动态变化的科学,是在蛋白质水平上定量的、动态的、整体的研究生物体。目前蛋白质组学技术分为样品制备、分离和鉴定3个方面,其新技术主要有激光捕捉显微解剖法、离心超滤法、双向凝胶电泳、同位素亲和标签技术、色谱技术以及质谱技术等。然而,任何一种蛋白质组学研究技术都有其缺陷。因此多种技术的联合应用能使蛋白质组研究更精确和完整,是蛋白质组学的发展趋势。     

肺癌患者体液生物标志物的蛋白质组学研究现状

肺癌是人类癌症死亡的首要原因.为了早期检测、监测肺癌,探寻肺癌的蛋白生物标志物成为近年来的研究热点.蛋白质组学,尤其是定量蛋白质组学可以在复杂生物样品中鉴定和定量蛋白质/多肽,用于肿瘤相关蛋白的研究.体液样本容易收集,治疗过程中可反复留取,越来越多的被用于发现肺癌潜在标志物的研究.本文就蛋白质组学在肺癌体液中的标志物研究做一简要综述.     

基于液质联用的单细胞蛋白质组学研究进展

蛋白质是细胞功能的主要执行者,由于其无法在体外进行扩增,单细胞蛋白质组学技术相较单细胞基因组学和转录组学技术而言发展相对滞后。传统的蛋白质组学技术可获得大量细胞蛋白表达的平均值,但忽略了细胞亚型及细胞异质性等信息。单细胞水平的蛋白质分析有助于阐明细胞不同表型与异质性的分子基础。随着质谱仪的快速发展,基于质谱的方法将单细胞蛋白质组学推向新的高度。本文综述了近年来基于液质联用方法的单细胞蛋白质组学在单细胞挑选、样品前处理、同位素标签技术、肽段分离、质谱采集、数据分析等方面的研究进展,及其在生物医学研究中的应用,并对未来单细胞蛋白质组学面临的挑战和发展前景进行了展望。单细胞蛋白质组学技术的进步将为生物医学研究领域提供新的思路和解决方案,并加深我们对人类健康和疾病的理解。     

Proteomics: a new approach to the study of disease

The global analysis of cellular proteins has recently been termed proteomics and is a key area of research that is developing in the post-genome era. Proteomics uses a combination of sophisticated techniques including two-dimensional (2D) gel electrophoresis, image analysis, mass spectrometry, amino acid sequencing, and bio-informatics to resolve comprehensively, to quantify, and to characterize proteins. The application of proteomics provides major opportunities to elucidate disease mechanisms and to identify new diagnostic markers and therapeutic targets. This review aims to explain briefly the background to proteomics and then to outline proteomic techniques. Applications to the study of human disease conditions ranging from cancer to infectious diseases are reviewed. Finally, possible future advances are briefly considered, especially those which may lead to faster sample throughput and increased sensitivity for the detection of individual proteins.     

蛋白质组学技术在心血管疾病中的应用

蛋白质组学是研究蛋白质组的一个新兴科学,主要采用双向凝胶电泳、质谱分析、蛋白质芯片和生物信息学等高通量、自动化技术研究组织或细胞全部蛋白质变化。蛋白质组学技术已广泛应用于心力衰竭、冠心病、高血压、心肌肥厚、心肌病和心肌缺血再灌注等心血管疾病的发病机制研究,发现了以蛋白质组变化为特征的新发病机理,为药物防治提供了新的思路和方法。 基金     

Proteomics and enriched biological processes in Antiphospholipid syndrome: A systematic review

Identification of differentially expressed proteins in antiphospholipid syndrome (APS) is a developing area of research for unique profiles of this pathology. Advances in technologies of mass spectrometry brings improvements in proteomics and results in assessment of soluble or cellular proteins which could be candidates for clinical biomarkers of primary APS. The use of blood as a source of proteins ease the acquisition of samples for proteomics analyses and later for disease diagnosis. We performed a systematic review to explore the proteomics studies carried out in circulating released proteins (serum, plasma) or cellular proteins (monocytes and platelets) of APS patients. The study groups differentiate among clinical APS cases with the aim to translate molecular findings to disease stratification and to improve APS diagnosis and prognosis. These studies also include the unravelling of new autoantibodies in non-criteria APS or how post-translational protein modifications provides clues about the pathological mechanisms of antigen-autoantibody recognition. Herein, we identified 82 proteins that were dysregulated in APS across eleven studies. Enrichment analysis revealed its connection to cellular activation and degranulation that eventually leads to thrombosis as the main biological process highlighted by these studies. Validation of APS-relevant proteins by functional and mechanistic studies will be essential for patient stratification and the development of targeted therapies for every clinical subtype of APS.     

蛋白质组学研究方法及其在生物医学中的应用

蛋白质组学方法发展迅速，并日见成熟。蛋白芯片技术、双向电泳—质谱技术、多维液相色谱—质谱技术等，已被广泛应用于寻找疾病相关的差异表达蛋白质、疾病相关的生物标记分子以及药物靶点用于临床诊断、药物设计、以及疾病发病机理的研究等。本文对上述研究进展作了简要综述。     

Redox proteomics

Abstract Proteins are major targets of reactive oxygen and nitrogen species (ROS/RNS) and numerous post-translational, reversible or irreversible modifications have been characterized, which may lead to a change in the structure and/or function of the oxidized protein. Redox proteomics is an increasingly emerging branch of proteomics aimed at identifying and quantifying redox-based changes within the proteome both in redox signaling and under oxidative stress conditions. Correlation between protein oxidation and human disease is widely accepted, although elucidating cause and effect remains a challenge. Increasing biomedical data have provided compelling evidences for the involvement of perturbations in redox homeostasis in a large number of pathophysiological conditions and aging. Research toward a better understanding of the molecular mechanisms of a disease together with identification of specific targets of oxidative damage is urgently required. This is the power and potential of redox proteomics. In the last few years, combined proteomics, mass spectrometry (MS), and affinity chemistry-based methodologies have contributed in a significant way to provide a better understanding of protein oxidative modifications occurring in various biological specimens under different physiological and pathological conditions. Hence, this Forum on Redox Proteomics is timely. Original and review articles are presented on various subjects ranging from redox proteomics studies of oxidatively modified brain proteins in Alzheimer disease and animal models of Alzheimer and Parkinson disease, to potential new biomarker discovery paradigm for human disease, to chronic kidney disease, to protein nitration in aging and age-related neurodegenerative disorders, electrophile-responsive proteomes of special relevance to diseases involving mitochondrial alterations, to cardiovascular physiology and pathology. Antioxid. Redox Signal. 17, 1487-1489.     

Redox proteomics identification of oxidized proteins in Alzheimer's disease hippocampus and cerebellum: an approach to understand pathological and biochemical alterations in AD

Alzheimer's disease (AD) is characterized by the presence of neurofibrillary tangles, senile plaques and loss of synapses. There is accumulating evidence that oxidative stress plays an important role in AD pathophysiology. Previous redox proteomics studies from our laboratory on AD inferior parietal lobule led to the identification of oxidatively modified proteins that were consistent with biochemical or pathological alterations in AD. The present study was focused on the identification of specific targets of protein oxidation in AD and control hippocampus and cerebellum using a redox proteomics approach. In AD hippocampus, peptidyl prolyl cis-trans isomerase, phosphoglycerate mutase 1, ubiquitin carboxyl terminal hydrolase 1, dihydropyrimidinase related protein-2 (DRP-2), carbonic anhydrase II, triose phosphate isomerase, alpha-enolase, and gamma-SNAP were identified as significantly oxidized protein with reduced enzyme activities relative to control hippocampus. In addition, no significant excessively oxidized protein spots were identified in cerebellum compared to control, consistent with the lack of pathology in this brain region in AD. The identification of oxidatively modified proteins in AD hippocampus was verified by immunochemical means. The identification of common oxidized proteins in different brain regions of AD brain suggests a potential role for these oxidized proteins and thereby oxidative stress in the pathogenesis of Alzheimer's disease.     

Candidate-based proteomics in the search for biomarkers of cardiovascular disease

The key concept of proteomics (looking at many proteins at once) opens new avenues in the search for clinically useful biomarkers of disease, treatment response and ageing. As the number of proteins that can be detected in plasma or serum (the primary clinical diagnostic samples) increases towards 1000, a paradoxical decline has occurred in the number of new protein markers approved for diagnostic use in clinical laboratories. This review explores the limitations of current proteomics protein discovery platforms, and proposes an alternative approach, applicable to a range of biological/physiological problems, in which quantitative mass spectrometric methods developed for analytical chemistry are employed to measure limited sets of candidate markers in large sets of clinical samples. A set of 177 candidate biomarker proteins with reported associations to cardiovascular disease and stroke are presented as a starting point for such a 'directed proteomics' approach.     

Advances in Proteomics of Mycobacterium leprae

Although Mycobacterium leprae was the first bacterial pathogen identified causing human disease, it remains one of the few that is non-cultivable. Understanding the biology of M. leprae is one of the primary challenges in current leprosy research. Genomics has been extremely valuable, nonetheless, functional proteins are ultimately responsible for controlling most aspects of cellular functions, which in turn could facilitate parasitizing the host. Furthermore, bacterial proteins provide targets for most of the vaccines and immunodiagnostic tools. Better understanding of the proteomics of M. leprae could also help in developing new drugs against M. leprae. During the past nearly 15 years, there have been several developments towards the identification of M. leprae proteins employing contemporary proteomics tools. In this review, we discuss the knowledge gained on the biology and pathogenesis of M. leprae from current proteomic studies.