PROJECT 3 : QUANTITATIVE BIOMARKERS OF DNA AND PROTEIN OXIDATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 项目3正在开发量化DNA、蛋白质和代谢物中氧化修饰的方法。我们将重点将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记物。这种标记是通过给细胞或动物添加标记的构建块来完成的，例如用于结合到蛋白质中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)结合到DNA和RNA中的核苷酸池氧化产物的特征和(2)在白细胞激活期间髓过氧化物酶产生的HOCl对蛋白质的氯化。完成这些目标将使量化氧化应激产生的分子的代谢流量这一总目标取得进展，氧化应激可能与癌症、糖尿病、动脉硬化和许多与衰老有关的疾病有关。

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.