Collaborative Projects In Environmental Health Sciences

工作概述：本项目包括质谱工作组与研究所内外其他小组合作解决共同关心的问题的努力。这些项目的主要重点是：1)未知化合物的结构测定；2)生物学途径的识别和/或确认；3)定量;4)开发生物重要化合物的分析策略。本项目不包括在严格的服务基础上执行的许多分析。我们继续与dr . Zeldin， LPP合作，在负离子化学电离（NICI）质谱下选择离子监测（SIM）鉴定和定量生理样品中的花生四烯酸代谢物。酶促花生四烯酸氧化的产物环氧二十碳三烯酸（EETs）和羟基二十碳三烯酸（HETEs）表现出显著的生物效应，既有有害的，也有有益的。在氧化过程中所涉及的酶的表征和酶的位置对于理解酶的功能意义是重要的。此外，参与花生四烯酸代谢的酶对环境挑战的反应可能是环境性疾病的重要因素/指标。我们已经鉴定了由新的p450形成的环氧二碳三烯酸，CYP2J9，在小鼠脑中发现，这种酶被观察到将花生四烯酸代谢为19-羟基二十碳四烯酸，从而与其他p450区分开来。发现它定位于小脑浦肯野细胞，并在19-HETE形成中活跃，19-HETE是一种抑制P/ q型Ca通道活性的类二十烷。环氧二碳三烯酸通过诱导组织纤溶酶原激活物具有纤溶特性，可能在调节血管止血中起作用。与C. Chignell， LPC一起，我们正在分析UVA和UVB辐射下存在和不存在抗生素lumifloxcin的DNA。

Summary of Work: This project includes those endeavors in which the mass spectrometry workgroup collaborates with other groups, both inside and outside the Institute to solve problems of mutual interest. The major focuses of these projects are: 1) structure determination of unknown compounds; 2) identification and/or confirmation of biological pathways; 3) quantitation; and 4) development of strategies for the analysis of biologically important compounds. Not included in this project are the many analyses performed on a strictly service basis. We continue to collaborate with D. Zeldin, LPP, on the identification and quantitation of arachidonic acid metabolites in physiological samples by selected ion monitoring (SIM) under negative ion chemical ionization (NICI) mass spectrometry. The products of enzymatically induced arachidonic acid oxidation, epoxyeicosatrienoic acids (EETs) and hydroxyeicosatrienoic acids (HETEs), exhibit significant biological effects, both harmful and beneficial. The characterization of the enzymes involved in the oxidation process and location of the enzymes is important in understanding the functional significance of the enzymes. Additionally, the response of the enzymes involved with arachidonic acid metabolism to environmental challenges may be a significant factor/indicator of environmentally induced disorders. We have characterized the epoxyeicosatrienoic acids formed by new P450s, CYP2J9, found in mouse brain This enzyme was observed to metabolize arachidonic acid to 19-hydroxyeicosatetraenoic acid distingusihing it form other P450s. It was found to be loacalized to cerebellar Purkinje cells, and active in 19-HETE formation, an eicosanoid that inhibits activity of P/Q-type Ca channels. Epoxyeicosatrienoic acids possess fribrinolytic properties through induction of tissue plasminogen activaotr and may play a role in regulating vascular hemostasis. With C. Chignell, LPC, we are analyzing DNA that has been subjected to UVA and UVB radiation in the presence and absence of the antibiotic lumifloxicin.