蛋白质组学及其在人类疾病研究中的应用

一、蛋白质组学的产生和概念以人类基因组“工作框架图”完成为标志 ,生命科学已进入了后基因组时代 ,生命科学研究的重心已从揭示生命的所有遗传信息转移到在分子整体水平对功能的研究上 ,从而产生了功能基因组学 (ｆｕｎｃｔｉｏｎａｌｇｅｎｏｍｉｃｓ)。但是基因仅是遗传信息的携带者 ,而生命功能的真正执行者是蛋白质 ,仅仅从基因的角度来研究是远远不够的。人类基因组测序草图显示 ,人类共有 3 0万～ 3 5万个基因 ,而与蛋白质合成有关的基因只占基因组的 2 % [1 ] ,如此有限和相对稳定的基因与蛋白质表达的时空多样性、动态性形成鲜明…     

蛋白质组学技术在消化疾病研究中的应用

随着人类基因组草图的初步完成,生命科学已经跨入“蛋白质组学”的新时代。蛋白质组学以基因组编码的所有蛋白为研究对象,从细胞水平及整体水平上研究蛋白质的组成及其变化规律,从而深入认识有机体的各种生理和病理过程。蛋白质组学主要包含3个方面:(1)表达蛋白质组学(expressi     

蛋白质组学在消化系疾病中医药研究中的应用

自然界各种生命物质都是由蛋白质组成的,各种蛋白质按不同的组成、结构和修饰,组成各种细胞和生命物质.蛋白质组学通过从整体角度分析细胞内动态变化的蛋白质组成、表达水平、修饰状况、蛋白质之间以及蛋白质与其他生物分子之间的相互作用,从而了解蛋白质的功能及其在生命过程中的作用.它包括双向凝胶电泳、生物质谱鉴定、生物信息学.当人体中某部分发生生理、病理变化时,该机体组织的蛋白质组发生变化,或代谢物的蛋白质组发生变化,就可以通过蛋白质组学技术找到这些新产生的蛋白质(称为"上调"或"表达增高)或减少甚至消失的蛋白质(称为"下调"或"表达降低"),这些蛋白质叫做"差异蛋白",是用于研究生理、病理变化诊断的潜在"靶点".     

蛋白质组学在肝脏疾病中的应用

蛋白质组学是系统研究分子体系、亚细胞系、细胞、组织、器官乃至整体水平蛋白质组成及其活动规律的一门学科。蛋白质组学技术为开展肝病研究建立了新的技术平台,并已成功筛选出一些具有潜在应用价值的蛋白标记物,用于肝病诊断和预后判断,同时发现一些新的药物治疗靶点,为肝脏疾病的诊断和治疗带来了新的机遇。本文旨在介绍蛋白质组学的相关研究技术及其在肝脏疾病研究中的应用。     

蛋白质组学技术在心血管疾病研究中的应用

蛋白质组学是现代科技的前沿,蛋白质芯片是20世纪末出现的最新一代生物芯片,因其高通量、高敏感、高效快捷等优点被广泛应用于生命科学领域,并取得一系列突破性进展。本文概述了蛋白质组学在心血管疾病的致病机制和临床治疗等相关领域的研究进展。     

蛋白质组学技术在慢性阻塞性肺疾病研究中的应用

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是全球范围常见疾病,其发病机制相当复杂,主要涉及氧化/抗氧化失衡、蛋白酶/抗蛋白酶失衡、炎症机制和细胞凋亡4个大的方面,而氧化/抗氧化失衡是COPD发生的关键机制,到目前为止COPD的发病机制仍然没有完全阐明.而蛋白质组学从整体的角度研究蛋白质,能精确地反映细胞、组织或器官中蛋白质动态变化,探寻疾病相关的标志物,为阐明发病机制提供新的线索.近年来,研究人员利用蛋白质组学技术从COPD患者支气管肺泡灌洗液、血清和血浆中寻找差异表达的蛋白质和疾病相关的标记分子.因此蛋白质组学这一新兴学科的产生,将为COPD的发病机制及治疗带来新的希望.本文就蛋白质组学在COPD研究中的应用作一简要综述.     

蛋白质组学在胰腺疾病研究中的应用

蛋白质组学是研究蛋白质的表达、翻译后修饰、在细胞内定位以及蛋白质与蛋白质之间的相互作用的科学。传统的研究手段主要采用双向凝胶电泳和质谱技术,前者用于蛋白质的分离,后者用于蛋白质的鉴定。目前新兴的研究技术主要有相差凝胶电泳技术同位素亲和标签技术。蛋白质组学在胰腺疾病的研究主要是通过正常个体与患病个体的血清、胰液或组织等进行蛋白质比较,发现差异蛋白质,从而对急、慢性胰腺炎和胰腺癌等胰腺疾病的发病机制、早期诊断和有效治疗提供理论依据和新思路。     

蛋白质组学在消化系肿瘤中的应用

蛋白质组学是以双向凝胶电泳和质谱技术为核心, 从整体的角度研究生物机体、组织、细胞甚至细胞器基因编码的全部蛋白质, 在更贴近生命本质的层次上发现和理解生命活动的规律.作为肿瘤研究的新平台, 蛋白质组学对食管癌、胃癌、肝癌、胰腺癌、结直肠癌等消化系肿瘤的早期诊断, 寻找新标志物, 治疗以及药物开发的新靶点等方面有重要意义, 具有潜在、广阔的应用前景.     

慢性肾脏病患者尿液蛋白质组学研究

2007年Khwaja等[1]研究报道慢性肾脏病(chronic kidney disease,CKD)患病率约为10%,其发病率仍呈逐年上升趋势.如何早期发现,早期诊断CKD并采取有效治疗措施延缓其进展,将成为人类面临的严峻挑战之一.     

磷酸化蛋白质组学在生命科学研究中的机遇与挑战

随着转化医学理念和研究思路的引入,以组学为基础的系统生物学解决复杂问题的优越性得以突显,即通过宏观思路,组装系统方案,解决微观问题,同时通过不同组学在不同研究层面的相互补充,加深了对生命真谛的认识.例如,早期医学研究主要集中在基因水平,由此提出基因组学研究思路,但随着人类基因组计划和全基因组测序完成,科学家们发现很多情况下染色体序列不同,甚至转录水平的变化并不导致表型改变,因而将目光投向基因翻译后的产物蛋白质,并提出蛋白质组学研究方法.磷酸化蛋白质组学是该领域的一个新分支,通过单次试验可以静态评估上千个蛋白的磷酸化情况,发现蛋白新的生理功能,更重要的是可以全局性地研究蛋白磷酸化的动力学变化,观察病理状态下不同蛋白间的相互作用及信号传导的变化,并为寻找药物靶点提供了全新的解决途径.本文将就磷酸化蛋白质组学的特点及其在生命科学中的应用前景作一简述.     

Toward the application of proteomics to human thyroid tissue.

CONTEXT: In this paper we describe for the first time a systematic approach to proteome analysis of human thyroid tissue. OBJECTIVE AND DESIGN: We report different methods to decrease the complexity of the human thyroid tissue proteome by applying different solubilization strategies and correcting for thyroglobulin protein abundance; to increase the protein resolution by prefractionation and by the use of narrow-range pH gradients; to detect proteins using sensitive and quantitative stains; and to identify soluble and membrane-bound thyroid tissue proteins by mass spectrometry analysis. MAIN OUTCOME/RESULTS: We found that buffers containing high contents of urea and detergents allow the best solubilization of human thyroid tissue proteins; highly variable abundance of thyroglobulin is a major pitfall of human thyroid proteome analysis, which in contrast to centrifugal ultrafiltration, size-exclusion chromatography and microdissection, can be countered best by adapting the protein amount to the thyroglobulin content per sample; prefractionation leads to a significant enrichment of proteins and allows subcellar localization of thyroid proteins; application of narrow-range immobilized pH gradient (IPG) strips allows further improvement of spot detection and separation; and protein detection with the fluorescent stain ruthenium II Tris bathophenanthroline disulfonate (RuBPs) is a highly sensitive and reliable tool for quantitative proteome analysis. Finally, in a pilot study of four patients with benign nodular thyroid disease we found that the described procedures allow a highly reproducible detection and identification of alterations in protein expression between nodular and corresponding normal thyroid tissues. CONCLUSIONS: Application of the described methods provides the basis for a highly sensitive and reproducible proteome analysis of the human thyroid, providing an additional novel tool to elucidate complex proteins changes in human thyroid biology as well as pathophysiology of human thyroid disease.     

Technology insight: the application of proteomics in gastrointestinal disease

Analysis of the human genome has increased our knowledge of the genes that are associated with disease. At the same time, however, it has become clear that having complete DNA sequences alone is not sufficient to elucidate the biological functions of the proteins that they encode. For this reason, proteomics-the analysis of proteins-has become increasingly attractive, because the proteome reflects both the intrinsic genetic programming of a cell and the impact of its immediate environment. The principal goals of clinical proteomics are to identify biomarkers for the early diagnosis of disease and potential targets for therapeutic intervention. Other goals include the identification of biomarkers for the early detection of disease recurrence (relapse) and how they might be combined with diagnostic imaging techniques to improve the sensitivity for detecting disease. This Review describes conventional proteomic technologies, their strengths and limitations, and demonstrates their application to clinical practice, with specific reference to their use in the gastroenterology field.     

肝脏疾病蛋白质组学研究进展

在我国大多数慢性肝病与病毒性感染有关,但目前的抗病毒治疗仍然存在总体疗效偏低、用药时间长、临床费用高及病毒变异等问题.     

Current application of proteomics in biomarker discovery for inflammatory bowel disease

Recently, the field of proteomics has rapidly expanded in its application towards clinical research with objectives ranging from elucidating disease pathogenesis to discovering clinical biomarkers. As proteins govern and/or reflect underlying cellular processes, the study of proteomics provides an attractive avenue for research as it allows for the rapid identification of protein profiles in a biological sample. Inflammatory bowel disease(IBD) encompasses several heterogeneous and chronic conditions of the gastrointestinal tract. Proteomic technology provides a powerful means of addressing major challenges in IBD today, especially for identifying biomarkers to improve its diagnosis and management. This review will examine the current state of IBD proteomics research and its use in biomarker research. Furthermore, we also discuss the challenges of translating proteomic research into clinically relevant tools. The potential application of this growing field is enormous and is likely to provide significant insights towards improving our future understanding and management of IBD.     

Application of proteomics to the study of cardiovascular biology

Proteomics involves the integration of a number of technologies with the aim of analyzing the complete complement of proteins expressed by a biological system in response to various stimuli and/or under different physiological or pathophysiological conditions. Recent technical improvements to the methods employed for protein separation and protein identification have resulted in a dramatic increase in the number of proteomics-based research projects. More importantly, it has become readily apparent that examining changes in the proteome offers insight into understanding cellular and molecular mechanisms that cannot be obtained through genomic analysis. There are numerous examples of cardiovascular functions whose molecular pathways are mediated through post-translational processes such as phosphorylation. The use of proteomics offers the ability to simultaneously monitor the changes in protein expression and/or cell signaling pathways in response to such conditions as cardiac hypertrophy and heart failure. Together with complementary genomic data, proteomics-based research can greatly increase our understanding of cardiovascular biology.     

The future of proteomics in the study of alcoholism

This article represents the proceedings of a workshop at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The workshop organizers/chairpersons were Chinnaswamy Kasinathan and Paul Manowitz. The presentations were (1) Introduction to the field of proteomics, by Kent Vrana; (2) Use of proteomics in the identification of urinary biomarkers for alcohol intake, by Chinnaswamy Kasinathan, Paul Thomas, and Paul Manowitz; (3) Proteomics screening illuminates ethanol-mediated induction of HDL proteins in macaques, by Kent Vrana, Randy Gooch, Travis Worst, Stephen Walker, Aaron Xu, Peter Pierre, Heather Green, and Kathleen Grant; and (4) Proteomics applied to the study of the liver, by Laura Beretta.     

疟原虫蛋白组学的研究进展

蛋白组学研究是疟原虫研究中的重要组成部分。近年来,随着蛋白质组研究中新思路和新技术的不断涌现,研究方法的不断改进和完善,蛋白组学研究技术已被广泛应用于疟原虫研究。为进一步了解疟原虫生物学特性及其与宿主相互作用机制,该文就疟原虫蛋白组学研究常用技术及其应用作一综述。     

Divide and conquer: the application of organelle proteomics to heart failure

Chronic heart failure is a worldwide cause of mortality and morbidity and is the final outcome of a number of different etiologies. This reflects both the complexity of the disease and our incomplete understanding of its underlying molecular mechanisms. One experimental approach to address this is to study subcellular organelles and how their functions are activated and synchronized under physiological and pathological conditions. In this review, we discuss the application of proteomic technologies to organelles and how this has deepened our perception of the cellular proteome and its alterations with heart failure. The use of proteomics to monitor protein quantity and posttranslational modifications has revealed a highly intricate and sophisticated level of protein regulation. Posttranslational modifications have the potential to regulate organelle function and interplay most likely by targeting both structural and signaling proteins throughout the cell, ultimately coordinating their responses. The potentials and limitations of existing proteomic technologies are also discussed emphasizing that the development of novel methods will enhance our ability to further investigate organelles and decode intracellular communication.