IDENTIFICATION AND CHARACTERIZATION OF BIOMARKERS OF ORGANOPHOSPHORUS EXPOSURES

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。子项目和 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。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 全球每年生产超过10亿磅的有机磷（OP）化学品，其中包括在美国喷洒的7000万磅农药。目前监测环境和职业接触毒死蜱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。OP磷酸三甲苯酯（TCP），它可以污染喷气发动机的引气，并导致商业航空公司的飞行员，机组人员和乘客的职业暴露的生物标志物，尚未identified.The我们的工作的目的是识别，纯化，并表征新的生物标志物的OP暴露。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更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更长持续时间后临床检测TCP和OP杀虫剂暴露。酰基肽水解酶（APH）是红细胞（RBC）胞浆丝氨酸蛋白酶，其从肽中去除N-乙酰化氨基酸并切割氧化蛋白。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和检测抑制CPS和代谢产物的TCP。RBC的120天寿命为检测暴露提供了更长的窗口。本研究利用功能蛋白质组学和酶活性分析方法，对神经毒性、环境和职业性OP暴露的生物标志物进行鉴定和表征。

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.