BIOMARKERS OF ORGANOPHOSPHOROUS EXPOSURE

有机磷暴露的生物标志物

• 批准号: 8171337
• 负责人: Clement Eugene Furlong
• 金额: $ 0.14万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171337
• 关键词: Active Sites; Air; Amino Acids; Biological Markers; Butyrylcholinesterase; Chemicals; Chlorpyrifos; Cleaved cell; Computer Retrieval of Information on Scientific Projects Database; Detection; Environmental and Occupational Exposure; Erythrocytes; Exposure to; Funding; Grant; Half-Life; Hemorrhage; Institution; Mass Spectrum Analysis; Methods; Molecular; Monitor; Occupational; Occupational Exposure; Peptides; Pesticides; Property; Proteins; Proteomics; Research; Research Personnel; Resources; Sensitivity and Specificity; Serine; Serine Protease; Source; Time; United States National Institutes of Health; Work; acylaminoacyl-peptidase; enzyme activity; inorganic phosphate; neurotoxic; organophosphorus insecticide

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. Over 1 billion pounds of organophosphorus (OP) chemicals are manufactured worldwide each year, including 70 million pounds of pesticides sprayed in the US. Current methods to monitor environmental and occupational exposures to OPs such as chlorpyrifos (CPS) have limitations, including low specificity and sensitivity, and short time windows for detection. Biomarkers for the OP tricresyl phosphate (TCP), which can contaminate bleed air from jet engines and cause an occupational exposure of commercial airline pilots, crewmembers and passengers, have not been identified. The aim of our work has been to identify, purify, and characterize new biomarkers of OP exposure. Butyrylcholinesterase (BChE) inhibition has been a standard for monitoring OP exposure. By identifying and characterizing molecular biomarkers with longer half-lives, we should be able to clinically detect TCP and OP insecticide exposure after longer durations of time than are currently possible. Acylpeptide hydrolase (APH) is a red blood cell (RBC) cytosolic serine proteinase that removes N-acetylated amino acids from peptides and cleaves oxidized proteins. Due to its properties, it is an excellent candidate for a biomarker of exposure. We have been able to purify APH and detect inhibition by both CPS and metabolites of TCP. The 120 day lifetime of the RBC offers a much longer window for detecting exposure. The OP-modified serine conjugate in the active site tryptic peptide has been characterized by mass spectrometry. This research uses functional proteomics and enzyme activities to identify and characterize useful biomarkers of neurotoxic environmental and occupational OP exposures.

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 对于中心来说，它不一定是研究者的机构。 全球每年生产超过 10 亿磅有机磷 (OP) 化学品，其中包括美国喷洒的 7000 万磅农药。目前监测环境和职业接触毒死蜱 (CPS) 等有机磷农药的方法存在局限性，包括特异性和灵敏度低、检测时间窗短等。 OP 磷酸三甲苯酯 (TCP) 的生物标志物尚未确定，该物质会污染喷气发动机的引气，并导致商业航空公司飞行员、机组人员和乘客发生职业暴露。 我们工作的目的是识别、纯化和表征 OP 暴露的新生物标志物。丁酰胆碱酯酶 (BChE) 抑制已成为监测 OP 暴露的标准。通过识别和表征具有较长半衰期的分子生物标志物，我们应该能够在比目前可能的持续时间更长的时间内临床检测 TCP 和 OP 杀虫剂暴露。 酰肽水解酶 (APH) 是一种红细胞 (RBC) 胞浆丝氨酸蛋白酶，可去除肽中的 N-乙酰化氨基酸并裂解氧化蛋白质。由于其特性，它是暴露生物标志物的绝佳候选者。我们已经能够纯化 APH 并检测 CPS 和 TCP 代谢物的抑制作用。红细胞的 120 天寿命为检测暴露提供了更长的窗口。活性位点胰蛋白酶肽中的 OP 修饰丝氨酸缀合物已通过质谱法进行了表征。 这项研究利用功能蛋白质组学和酶活性来识别和表征神经毒性环境和职业有机磷暴露的有用生物标志物。