FISH OIL HYDROXY FATTY ACIDS AS CELLULAR MODULATORS

流行病学证据表明，富含鱼油脂质的饮食 与冠状动脉血管病变的发生率降低有关 疾病 这些特殊的 膳食成分产生的观察结果是未知的， 许多研究表明，n-3多不饱和脂肪酸 来自鱼类的多不饱和脂肪酸（PUFAs）可调节花生四烯酸 代谢导致白三烯、前列腺素和其他 生物活性产品。 虽然n-3 PUFA可以 直接干扰n-6类花生酸的形成，另一种 有吸引力的假设是n-3 PUFA的代谢产生 某些产品是各种疾病的实际调节剂 代谢过程 当PUFA被细胞代谢时， 脂肪氧合酶，单羟基脂肪酸（HOFA）通常是 最丰富的产品形成。 我们和其他团体一样， 已经发现源自花生四烯酸（HETE）的HOFA 调节各种生物反应和过程。 是 本提案的目的是评价 几种HOFA源自鱼油n-3 PUFA。 我们建议合成六种不同的鱼油HOFA（FHOFA） 从二十碳五烯酸和二十二碳六烯酸， 研究这些FHOFA对各种 释放和代谢花生四烯酸的酶，包括 血小板和嗜中性粒细胞磷脂酶、环加氧酶和 脂氧合酶 将从人类和大鼠供体中分离细胞 正常饮食以及捐赠者的饮食将 补充鱼油，以确定是否 细胞脂质含量影响细胞膜的调节特性， FHOFA。 我们还将调查这些FHOFA是否容易 以及这些FHOFA是否 对中性粒细胞趋化，影响钙稳态， 血小板和中性粒细胞聚集。 希望这些研究将为我们提供新的见解， 存在于海产品中的n-3多不饱和脂肪酸 影响某些代谢过程。 此外，结果 从拟议的研究可以提出新的战略， 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.