COLLABORATIVE PROJECTS IN ENVIRONMENTAL HEALTH SCIENCES

环境健康科学合作项目

• 批准号: 6106702
• 负责人: Kenneth Tomer
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6106702
• 关键词: arachidonate; biological signal transduction; chemical structure function; cytochrome P450; eicosanoid metabolism; environmental health; enzyme activity; hormone receptor; human tissue; laboratory rat; mass spectrometry; oxygenases; retinoate; thyroid hormones; vitamin D; vitamin receptor

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 structure determination of biologically important compounds. Current major collaborative projects under way include: 1)quantitation of hydroxyoctadecadienoic acid and hydroxyeicosanoic acids in cells; 2) quantitation of arachidonic acid metabolites (D. Zeldin, LPP). Quantitation of Arachidonic Acid Metabolites - The most sensitive and accurate method for quantitation of eicosanoids in physiological samples is by selected ion monitoring (SIM) under negative ion chemical ionization (NICI) mass spectrometry. We are currently quantifying eicosanoid metabolites as part of several studies. These include: Characterization of the arachidonic acid metabolites of a new cytochrome P450, CYP2J5, isolated from a mouse liver cDNA library and abudantly expressed within tubules of the renal cortex. CYP2J5 arachidonic acid oxidation products are postulated to play important functional roles in the kidney. Determination of the variations in arachidonic acid metabollism as a function of changes in P450 function occurring during fasting and refeeding in rats. Characterization of arachidonic acid metabolites in fish as characterization of the alteration of endogenous arachidonic acid metabolism as a function of being challenged with TCDD and BP. Characterization of the CYP2J subfamily cytochrome P450s in the human jejunum. 15-lo is highly expressed in human colorectal tumors. The function of 15-lo expression is being investigated in caco-2 cells. The 15-lo is expressed during Na butyrate induced apoptosis and cell differentiation. Inhibition of 15-lo enhances the NaBT induced apoptosis. Metabolism studies using cell lysates indicate a shift in exogenous metabolism of AA and LA to 15-HETE and 13-HODE. The time course for the formation of 15-HETE and 13-HODE during the induction of cell differentiation and apoptosis is being determined as a means of determining the function of 15-lo expression in these cells.

工作摘要：该项目包括 质谱工作组合作的努力 与研究所内外的其他团体一起解决 相互兴趣的问题。这些项目的主要重点 是：1）未知化合物的结构测定； 2） 鉴定和/或确认生物途径； 3） 定量； 4）制定结构的策略 确定生物学上重要的化合物。当前专业 正在进行的协作项目包括：1）定量 细胞中的羟基二十二烯酸和羟基乙酸； 2）定量花生四烯酸代谢物（D. Zeldin，LPP）。 蛛网膜酸代谢物的定量 - 最敏感的 和准确定量eicosanoids中的方法 生理样品是通过选定的离子监测（SIM）下的 负离子化学电离（NICI）质谱法。我们是 目前正在量化eicosanoid代谢物作为几个 研究。其中包括：蛛网膜酸的表征 从A分离的新细胞色素P450，CYP2J5的代谢产物 小鼠肝cDNA文库，在小管中表达 肾皮质。 CYP2J5花生四烯酸氧化产物 假设将在肾脏中扮演重要的功能角色。 确定蛛网膜酸代谢的变化作为一种 P450功能在禁食期间发生的变化的功能 在老鼠中喂食。 蛛网膜酸代谢产物的表征 在鱼中作为内源性改变的特征 蛛网膜酸代谢是受到挑战的函数 TCDD和BP。 CYP2J亚科的表征 人类空肠中的细胞色素P450。 15-lo高度表达 在人类结直肠肿瘤中。 15-LO表达的功能是 在CACO-2细胞中进行了研究。 15-LO在Na期间表示 丁酸酯诱导凋亡和细胞分化。抑制 15-LO增强了NABT诱导的凋亡。代谢研究 使用细胞裂解物表明AA的外源代谢发生了变化 以及LA到15-HETE和13-hode。时间课程 在诱导细胞期间形成15-Hete和13-hode 分化和凋亡被确定为 确定这些细胞中15-LO表达的功能。