Bioactive lipid mediators and reactive oxygen species

生物活性脂质介质和活性氧

• 批准号: 7142874
• 负责人: ROBERT Carl MURPHY
• 金额: $ 37.28万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7142874
• 关键词: apoptosis; cell membrane; cholesterol; electrospray ionization mass spectrometry; environmental exposure; free radical oxygen; glycerophosphates; lipid structure; lipids; mass spectrometry; matrix assisted laser desorption ionization; oxidation; ozone; phosphatidylserines; plasmalogens; technology /technique development

The generation of biologically active lipid messengers by cellular biochemical processes is often under considerable biochemical regulation. However, biologically active lipids are also generated, in an unregulated mode, by the interaction of reactive oxygen species with lipid precursors present in the membranes of cells. The structural analysis and quantitation of these lipid mediators requires the development of sophisticated yet nonspecific analytical techniques that are capable of providing specific data for lipids while they are present in complex mixtures of closely related compounds. Mass spectrometry is such a tool. A major objective of this grant is to further develop sophisticated mass spectrometry including electrospray ionization and MALDI ionization techniques suitable for the qualitative and quantitative analysis of lipid mediators derived from cellular membranes following exposure to reactive oxygen species. The potential for mass spectrometry as a tool used for imaging lipids in tissues will also be investigated with the intent to apply mass spectrometric imaging to determine the precise localization of oxysterols in pulmonary airways following exposure of mice to environmentally relevant concentrations of ozone. One important specific goal is to understand the molecular basis underlying the toxicity of ozone in the lung. The oxidation of cholesterol by ozone and the formation of active oxysterols will be further examined. The reaction of ozone with plasmalogen glycerophospholipids will also be investigated in studies to test the hypothesis that vinyl ether phospholipids serve an important role in protecting cells from potentially toxic reactions of ozone following reactions with other endogenous lipids. The oxidation of phosphatidylserine and glycerophosphoethanolamine lipids during the process of cellular apoptosis will also be investigated. The specific goal will be to identify and structurally characterize oxidized phosphatidylserine and probe the mechanism of formation and potential biological functions of these oxidized lipids including the role they play in apoptosis. The studies in this portion of the program project grant complements the other projects in the broad sense of understanding mechanisms of lipid mediator production, regulation, and action.

由细胞生化过程产生的生物活性脂质信使通常受到相当大的生化调节。然而，生物活性脂质也是通过活性氧物种与存在于细胞膜中的脂质前体相互作用而以一种不受调控的方式产生的。这些脂类介体的结构分析和定量需要开发复杂但非特异性的分析技术，当脂类存在于密切相关化合物的复杂混合物中时，这些技术能够提供特定的数据。质谱学就是这样一种工具。这笔赠款的一个主要目标是进一步开发复杂的质谱学，包括电喷雾电离和MALDI电离技术，适用于在暴露于活性氧物种后对细胞膜中的脂质介体进行定性和定量分析。这个 还将研究质谱仪作为组织中脂质成像工具的可能性，目的是应用质谱仪成像来确定小鼠暴露于环境相关浓度的臭氧后，氧合甾醇在肺呼吸道中的精确定位。一个重要的具体目标是了解臭氧对肺部毒性的分子基础。我们将进一步研究臭氧对胆固醇的氧化和活性氧化甾醇的形成。臭氧与血浆甘油磷脂的反应也将在研究中被调查，以检验这一假设 乙烯基醚磷脂在保护细胞免受臭氧与其他内源性脂质反应后的潜在毒性反应方面发挥着重要作用。此外，还将研究细胞凋亡过程中磷脂酰丝氨酸和甘油磷乙醇胺类脂的氧化情况。具体的目标将是鉴定和结构表征氧化的磷脂酰丝氨酸，并探索这些氧化脂质的形成机制和潜在的生物学功能，包括它们在细胞凋亡中所起的作用。这个 该计划项目拨款这一部分的研究在广义上补充了其他项目，以了解脂质介体的产生、调节和作用的机制。