FISH OIL HYDROXY FATTY ACIDS AS CELLULAR MODULATORS

流行病学证据表明，富含鱼油脂肪的饮食 与冠状动脉血管发病率的降低有关 疾病。这些特殊生物所通过的确切机制 饮食成分产生的观察结果尚不清楚，但 多项研究表明，n-3多不饱和脂肪酸 鱼中多不饱和脂肪酸对花生四烯酸的调节作用 新陈代谢导致白三烯、前列腺素和其他 生物活性产品。尽管n-3个PUFA可能 直接干扰n-6二十烷类化合物的形成，另一个 有吸引力的假设是n-3多不饱和脂肪酸的新陈代谢产生 某些产品是各种不同的实际调制器 代谢过程。当多不饱和脂肪酸被细胞代谢时 脂肪氧合酶，单羟基脂肪酸(HOFA)通常是 形成了最丰富的产品。我们和其他团体一样， 已发现HOFAs源自花生四烯酸(HETE) 调节各种生物反应和过程。它是 本提案的目的是评价细胞的生物学特性。 几种从鱼油中提取的高不饱和脂肪酸n-3PUFA。 我们建议合成六种不同的鱼油HOFAs(FHOFAs) 从二十碳五烯酸和二十二碳六烯酸 考察这些FHOFA对不同物种的调控作用 释放和代谢花生四烯酸的酶包括 血小板和中性粒细胞磷脂酶、环氧合酶和 脂肪氧合酶。将从人类和大鼠捐赠者身上分离出细胞 正常饮食和捐赠者的饮食将是 补充鱼油，以确定是否 细胞内脂质含量影响细胞的调节特性 FHOFA。我们还将调查这些FHOFA的准备程度 以及这些FHOFA是不是 趋化中性粒细胞，影响钙稳态和 血小板和中性粒细胞聚集。 希望这些研究将为我们提供对 N-3多不饱和脂肪酸存在于海产品中的机制， 影响某些新陈代谢过程。此外，结果显示， 从拟议的研究中可以提出新的战略 治疗和/或预防炎症和心血管疾病 疾病。

Epidemiological evidence suggests that diets rich in fish oil lipids are associated with decreased incidence of coronary vascular disease. The exact mechanisms through which these special dietary components produce the observed results are unknown but a number of studies indicate that n-3 polyunsaturated fatty acids (PUFAs) derived from fish may modulate arachidonic acid metabolism leading to leukotrienes, prostanoids and other biologically active products. Although the n-3 PUFAs could directly interfere with the formation of n-6 eicosanoids, another attractive hypothesis is that metabolism of n-3 PUFAs produces certain products which are the actual modulators of various metabolic processes. When PUFAs are metabolized by cellular lipoxygenases, monohydroxy fatty acids (HOFAs) are usually the most abundant products formed. We, as well as other groups, have found that HOFAs derived from arachidonic acid (HETEs) regulate a variety of biological responses and processes. It is the objective of this proposal to evaluate the biological properties of several HOFAs derived from fish oil n-3 PUFAs. We propose to synthesize six different fish oil HOFAs (FHOFAs) from eicosapentaenoic acid and docosahexaenoic acid and to examine the regulatory effects of these FHOFAs on various enzymes that release and metabolize arachidonic acid including platelet and neutrophil phospholipases, cyclooxygenases and lipoxygenases. Cells will be isolated from human and rat donors on normal diets as well as from donors whose diets will be supplemented with fish oil in order to determine whether the cellular lipid content influences the modulatory properties of the FHOFAs. We will also investigate how readily these FHOFAs are incorporated into cellular lipids and whether these FHOFAs are chemotactic for PMNs, influence calcium homeostasis and platelet and neutrophil aggregation. It is hoped that these studies will provide new insights into the mechanisms through which n-3 PUFAs, present in seafoods, influence certain metabolic processes. In addition, the results from the proposed studies could suggest new strategies for the treatment and/or prevention of inflammatory and cardiovascular diseases.