MECHANISMS OF DISEASE PREVENTION BY OMEGA-3 FATTY ACIDS

本研究的目的是了解鱼油脂肪的机制， 酸可以影响细胞对正常激动剂和有害物质的反应。 剂. 有充分的证据表明，长链多不饱和n-3或 n-6脂肪酸（PUFA）可以影响许多不同的细胞过程。 含有鱼或鱼油的饮食会改变一些炎症，免疫， 和动脉粥样硬化过程。 这些影响可能是由于 类二十烷酸、类二十二烷酸、白三烯、脂氧素或P450的差异 由二十碳五烯酸产生的代谢物EPA（C20：5 n-3），和 二十二碳六烯酸，DHA（C22：6 n-3），当它们取代花生四烯酸时， AA（C20：4 n-6）在膜磷脂的sn-2位。 或者，它们可能是直接由于功能的变化， 膜结合蛋白质（酶、受体、转运通道） 从他们的磷脂微环境与EPA和DHA的富集。 细胞功能的变化是如何由这些细微的变化引起的？ 磷脂脂肪酸还不清楚。 我们已经证明，用EPA或DHA富集分离的大鼠心肌细胞， (in与n-6 AA相反）在体外完全保护心肌细胞免受 高浓度强心苷（10-4 M哇巴因）的毒性。 EPA或DHA防止细胞溶质钙的致命水平，以应对有毒的 通过阻断钙进入肌细胞来降低哇巴因的浓度。 这种保护作用的机制可以通过进一步的研究来阐明 in our models模型systems系统. 美国每年有50万人死于心脏病发作 在受害者到达医院之前， 根据美国心脏协会。 其中绝大多数 “猝死”是由于心室纤维性颤动。 因此，我们的研究 了解鱼油脂肪酸防止 心肌细胞的心律失常可能具有潜在的公共健康 重要性

The object of this study is to learn the mechanisms by which fish oil fatty acids can affect the responses of cells to normal agonists and noxious agents. There is ample evidence that the long chain polyunsaturated n-3 or n-6 fatty acids (PUFA) can affect differently many cellular processes. Diets containing fish or fish oils alter some inflammatory, immunologic, and atherosclerotic processes. These effects could be due to the differences in eicosanoids, docosanoids, leukotrienes, lipoxins, or P450 metabolites produced from eicosapentaenoic acid, EPA (C20:5n-3), and docosahexaenoic acid, DHA (C22:6n-3), when they replace arachidonic acid, AA (C20:4n-6) in the sn-2 position of membrane phospholipids. Alternatively, they could be due directly to changes in the function of membrane-bound proteins (enzymes, receptors, transport channels) resulting from enrichment of their phospholipid microenvironment with EPA and DHA. How changes in cellular functions are induced by these subtle changes of phospholipid fatty acids is not yet understood. We have shown that enriching isolated rat cardiac myocytes with EPA or DHA (in contrast to n-6 AA) in vitro completely protects the myocytes against toxicity from a high concentration of cardiac glycosides (10-4 M ouabain). EPA or DHA prevents lethal levels of cytosolic calcium in response to toxic concentrations of ouabain by blocking entry of calcium into the myocytes. The mechanism of this protective effect can be clarified by further studies in our model systems. Of the half million deaths from heart attacks annually in the United States, 300,000 deaths will occur before the victims get to a hospital, according to the American Heart Association. The great majority of these "sudden deaths" are due to ventricular fibrillation. Thus our studies to understand the mechanisms by which the fish oil fatty acids prevent arrhythmias of cardiac myocytes may have potential public health importance.