PROJECT 3 : QUANTITATIVE BIOMARKERS OF DNA AND PROTEIN OXIDATION

项目 3：DNA 和蛋白质氧化的定量生物标志物

• 批准号: 7724078
• 负责人: Paul Thomas Henderson
• 金额: $ 29.81万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7724078
• 关键词: Amino Acids; Animals; Arteriosclerosis; Biological; Biological Markers; Cells; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA biosynthesis; DNA chemical synthesis; Diabetes Mellitus; Disease; Dose; Funding; Goals; Grant; Institution; Isotope Labeling; Label; Leukocytes; Malignant Neoplasms; Metabolic; Methods; Modification; Nucleosides; Nucleotides; Oxidative Stress; Pathway interactions; Peroxidase; Proteins; RNA; Research; Research Personnel; Resources; Source; United States National Institutes of Health; age related; chlorination; human disease; oxidation; protein metabolite

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. Project 3 is developing methods to quantify oxidative modifications in DNA, proteins, and metabolites. We will focus on introducing 14C isotope labels into biological molecules in order to characterize pathways and biomarkers of relevance to human disease. This labeling is done by either dosing cells or animals with a labeled building block such as an amino acid for incorporation into proteins or a nucleoside for synthesis of DNA. Two main objectives of Project 3 are: (1) characterization of nucleotide pool oxidation products that are incorporated into DNA and RNA and (2) chlorination of proteins by HOCl produced by myeloperoxidase during the activation of white blood cells. Completion of these objectives will enable progress towards the general goal of quantifying the metabolic flux of molecules produced as a result of oxidative stress which may be related to cancer, diabetes, arteriosclerosis and numerous aging-related diseases.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 项目 3 正在开发量化 DNA、蛋白质和代谢物氧化修饰的方法。 我们将专注于将 14C 同位素标记引入生物分子中，以表征与人类疾病相关的途径和生物标志物。 这种标记是通过给细胞或动物添加标记的构件来完成的，例如用于掺入蛋白质的氨基酸或用于合成 DNA 的核苷。 项目 3 的两个主要目标是：(1) 掺入 DNA 和 RNA 的核苷酸库氧化产物的表征，以及 (2) 白细胞激活过程中髓过氧化物酶产生的 HOCl 对蛋白质进行氯化。 这些目标的完成将有助于实现量化氧化应激产生的分子代谢通量的总体目标，氧化应激可能与癌症、糖尿病、动脉硬化和许多与衰老相关的疾病有关。