OXIDATIVE POST-TRANSLATIONAL MODIFICATIONS IN CARDIOVASCULAR DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 NHLBI赞助的血管蛋白质组学中心的研究重点是与心血管疾病相关的氧化翻译后修饰。核心实验室开发适当的方法，并提供二维凝胶分离或多级HPLC纯化蛋白质样品中肽的capLC-QTOF分析。结合资源，还进行了MALDI-TOF MS，LTQ-Orbitrap MS/MS和FTMS质谱分析。该中心正在制作协助数据处理和解释的软件。一种新型的VC-MALDI低温傅里叶变换质谱仪与14-T磁铁正在建设，使高通量，高性能的分析蛋白质水解混合物的生物来源，并有效，准确地确定其翻译后修饰。基础和临床研究人员，主要位于BUSM和HMS，正在使用蛋白质组学方法来研究氧化应激对细胞培养物，组织和整个生物体的影响。在本报告年度，除了大量的口头和海报会议介绍外，还发表了两篇涉及资源合作的方法论文，一篇关于生物信息学，另一篇关于新型疏水氟衍生物，此外还发表了探索FTMS方法的应用论文，合作产生了关于血小板刺激途径和sirtuin氧化修饰的论文。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The research of the NHLBI-sponsored Cardiovasculaar Proteomics Center focuses on the oxidative post-translational modifications that occur in conjunction with cardiovascular disease. The Core laboratory develops appropriate methods and provides capLC-QTOF analysis of peptides in digests of 2D-gel separated or multistage HPLC purified proteins. In conjunction with the Resource, MALDI-TOF MS, LTQ-Orbitrap MS/MS and FTMS mass spectral analyses are also carried out. Software to assist in data processing and interpretation is being generated in the Center. A novel VC-MALDI cryogenic Fourier transform mass spectrometer with a 14-T magnet is being constructed to enable high throughput, high performance analysis of proteolysis mixtures from biological sources, and efficient, accurate determination of their post-translational modifications. Basic and clinical investigators, primarily located at BUSM and HMS, are using proteomic approaches to investigate the effects of oxidative stress on cell cultures, tissues and whole organisms. During this reporting year, in addition to numerous oral and poster meeting presentations, two methods papers that involved Resource collaboration, one on bioinformatics and one on novel hydrophobic fluorous derivatives, were published, in addition to applications papers that explored FTMS methods, and collaborations yielded papers on platelet stimulation pathways and oxidative modification of sirtuin.