Identifying the targets of myeloperoxidase-derived oxidants in plasma and cells

髓过氧化物酶（MPO）是一种血红素酶，由活化的白细胞释放，催化产生高度有害的氯化氧化剂。众所周知，这些氧化剂通过杀死细菌和其他入侵的病原体，在人体免疫系统中发挥着重要作用。然而，过量或错位生成这些氧化剂会导致组织损伤。这种损害与疾病的发展有关。例如，有强有力的证据表明MPO及其产生的氧化剂与动脉粥样硬化有关。这种疾病导致大约40%的澳大利亚人死亡。毫无疑问，MPO产生的氧化剂对组织造成重大损害和广泛的细胞死亡。然而，由于缺乏检测氧化介导的单个靶分子损伤的敏感和特异性技术，这一过程中涉及的机制仍有待建立。本研究将利用新的标记技术确定血浆和细胞中mpo衍生氧化剂的关键靶点。这将为氧化损伤和细胞毒性机制提供有价值的信息。这对于设计潜在的治疗药物来调节和预防与MPO相关的退行性疾病（如动脉粥样硬化）的进展将是重要的。

Myeloperoxidase (MPO) is a haem enzyme, released by activated white blood cells, that catalyses the production of highly damaging chlorinated oxidants. These oxidants are known to play a major role in the human immune system by killing bacteria and other invading pathogens. However, excessive or misplaced generation of these oxidants results in tissue damage. This damage has been implicated in development of disease. For example, there is strong evidence for the involvement of MPO, and the oxidants that it produces, in atherosclerosis. This disease is responsible for the death of around 40 % of the Australian population. There is no doubt that the oxidants produced by MPO cause major damage to tissues and extensive cell death. However, the mechanisms involved in this process remain to be established, due to a lack of sensitive and specific techniques for examining oxidant-mediated damage to individual target molecules. This study will identify the key targets of MPO-derived oxidants in plasma and cells using novel labelling techniques. This will provide valuable information about the mechanisms of oxidative damage and cytotoxicity. This will be important in the design of potential therapeutic agents to modulate and prevent the progression of degenerative diseases, such as atherosclerosis, that are linked with MPO.