Novel omega-3 fatty acid epoxides and the activation of cellular survival pathways

新型 omega-3 脂肪酸环氧化物和细胞生存途径的激活

• 批准号: nhmrc : 402496
• 负责人: Prof Michael Murray
• 金额: $ 30.49万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/novel-omega-3-survival-pathways/96605
• 关键词: Novel; omega; fatty; acid; epoxides

Recent studies have reported that foods and oils containing high levels of omega-3 fatty acids have beneficial effects in patients with arthritis and cardiovascular disease. The mechanisms by which these dietary changes produce health benefits are unclear but it is known that omega-3 fatty acids can replace omega-6 and other fatty acids in cells; these omega-6 acids are more common in western diets. A number of enzymes in cells convert fatty acids to oxygenated derivatives and some of these have potent protective effects that allow cells to survive in the presence of toxic stimuli. We have found that epoxides formed from the omega-3 fatty acid stearidonic acid are extremely potent protective agents in cells - more so that epoxides from omega-6 acids like arachidonic acid. The present project seeks to identify omega-3 fatty acid epoxides with potent and long-lived beneficial effects in cells, relate these properties to those of omega-6 fatty acid epoxides and then understand how the omega-3 epoxides enhance cell survival. The findings will provide a rational basis from which to understand the beneficial effects of dietary modification already seen in clinical studies. By understanding the biochemical and molecular events in cells that are activated by omega-3 fatty acid epoxides we may be able to design therapies, most likely involving changes in dietary fat intake, that could benefit individuals with arthritic, cardiovascular and other conditions. Given the high incidence of these conditions in this country the potential impact of the findings from this project could be highly significant and are consistent with the national research priority healthy ageing.

最近的研究报告说，含有高水平欧米茄-3脂肪酸的食物和油对关节炎和心血管疾病患者有有益的影响。这些饮食变化产生健康益处的机制尚不清楚，但已知omega-3脂肪酸可以取代细胞中的omega-6和其他脂肪酸;这些omega-6酸在西方饮食中更常见。细胞中的许多酶将脂肪酸转化为含氧衍生物，其中一些具有有效的保护作用，使细胞能够在有毒刺激物的存在下存活。我们已经发现，由ω-3脂肪酸十八碳四烯酸形成的环氧化物是细胞中非常有效的保护剂-更重要的是，来自ω-6脂肪酸的环氧化物，如花生四烯酸。本项目旨在确定在细胞中具有有效和长期有益作用的omega-3脂肪酸环氧化物，将这些特性与omega-6脂肪酸环氧化物的特性相关联，然后了解omega-3环氧化物如何增强细胞存活。这些发现将为理解临床研究中已经看到的饮食调整的有益作用提供合理的基础。通过了解细胞中被omega-3脂肪酸环氧化物激活的生物化学和分子事件，我们可能能够设计治疗方法，最有可能涉及饮食脂肪摄入量的变化，这可能使关节炎，心血管和其他疾病的患者受益。鉴于这些疾病在该国的高发率，该项目研究结果的潜在影响可能非常显著，并与国家研究重点健康老龄化相一致。