4疾病蛋白质的组学.pptVIP

第四讲 疾病蛋白质组学（一） disease proteomics;一、基本概念和总体研究概况;疾病蛋白质组学disease proteomics;研究进展;存在问题和发展趋势;二、心血管疾病蛋白质组学 Cardiovascular Proteomics;Research Focus;The myofilament proteome;A simplified illustration of the cardiac myofilament proteins. The thick filament proteins consist of myosin heavy chain (MHC), myosin-binding protein C (MyBP-C), and two myosin light chains (MLC1 and MLC2). The thin filament proteins consist of actin, tropomyosin (Tm), and the three components of troponin; troponin I (TnI), troponin C (TnC) and troponin T (TnT). Phosphorylation sites on the myofilament proteins are indicated with a small diamond. The large scaffolding protein, titin, which spans the sarcomere, is not included in this illustration.;Structure of a region of the overlap region of a cardiac sarcomere in diastole on the left and during systole on the right with indications of major and functionally significant protein phosphorylation sites.;Post-translational modifications of myofilament proteins;;Sample preparation;Detection Methods for Protein modification;Immobilized metal affinity column (IMAC) ;Detection Methods for Protein modification;文献阅读;2. Redox modifications in the cardiac proteome;Outline of potential consequences of oxidative stress in cell system;Mechanisms of ROS generation. Sequential reduction of molecular oxygen to generate superoxide, hydrogen peroxide and then hydroxyl radical. List of amino acids particularly susceptible to modification.;Diagram showing the production of NO and RNS, with their effects on biological targets. At high concentrations, NO reacts mainly with oxygen superoxide forming peroxynitrite (ONOO) and peroxynitrous acid (ONOOH). In this way, NO is intimately linked with ROS. Moreover, the reaction of NO with O2 leads to the formation of the highly poisonous nitrogen dioxide (NO2), dinitrogen tetroxide (N2O4), or both. At low concentrations, the direct effects of NO predominate (dashed arrow) and haems and redox metals at iron–sulphur centr