PROJECT 3 : QUANTITATIVE BIOMARKERS OF DNA AND PROTEIN OXIDATION

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。 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。 我们将专注于将14 C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施用标记的结构单元来完成的，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）鉴定掺入DNA和RNA的核苷酸池氧化产物，以及（2）在白色血细胞活化过程中髓过氧化物酶产生的HOCl对蛋白质的氯化作用。 这些目标的完成将使得能够朝着量化由于氧化应激而产生的分子的代谢通量的总体目标取得进展，所述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。

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.