Collaborative Projects In Environmental Health Sciences

工作总结：该项目包括质谱分析师与研究所内外其他团体合作解决共同感兴趣的问题的努力。这些项目的主要重点是：1）未知化合物的结构测定; 2）生物途径的鉴定和/或确认; 3）定量;和4）开发用于分析生物重要化合物的策略。本项目中不包括在严格的服务基础上进行的许多分析。 我们将继续与D。Zeldin，LPP，在负离子化学电离（NICI）质谱下通过选择离子监测（SIM）鉴定和定量生理样品中的花生四烯酸代谢物。 花生四烯酸的酶促氧化产物环氧二十碳三烯酸和羟基二十碳三烯酸具有重要的生物学效应，既有有害的，也有有益的。参与氧化过程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诱导的疾病的重要因素/指标。我们对小鼠脑中发现的新的P450-CYP 2 J 9形成的环氧二十碳三烯酸进行了表征。发现其定位于小脑浦肯野细胞，并在19-HETE形成中具有活性，19-HETE是一种抑制P/Q型Ca通道活性的类花生酸。环氧二十碳三烯酸通过诱导组织纤溶酶原激活物而具有纤溶特性，并可能在调节血管止血中起作用。 梭Chignell，LPC，我们正在分析在存在和不存在抗生素荧光素的情况下受到UVA和UVB辐射的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.