CELL SIGNAL TRANSDUCTION AND N-3 FATTY ACIDS

描述：（改编自研究者摘要）。 人们日益 有证据表明，人类健康的好处，从消费 ω-3脂肪酸。 这些好处包括改善一些 病理状态（心血管疾病和肿瘤生长）和 提供正常生长所需的必需膳食化合物， 人类的发展。 虽然这些益处的机制尚不清楚， 它们可能是由这些脂肪酸对 利用脂质介质的细胞间信号传导机制 从膜磷脂。 这项建议的主要目的是 确定n-3脂肪酸对信号影响的性质 HL-60细胞中的信号转导通路。未分化的HL-60细胞，和 HL-60细胞用二甲基亚砜分化（嗜中性粒细胞样细胞） 和佛波醇酯（巨噬细胞样细胞）。这些细胞模型 将补充油酸（n-9）、花生四烯酸（n-6）、二十碳五烯酸（n-10）、 (n-3)和二十二碳六烯酸（n-3）。 补充和未补充 将用三种生理相关刺激刺激细胞 （甲酰甲硫氨酰亮氨酰苯丙氨酸，C5 a和血小板活化因子， PAF）和三种炎症反应（呼吸爆发 脱粒和PAF生物合成）。 在其中n-3脂肪酸 酸补充引起反应的变化，细胞脂质将 提取并分析以确定 磷脂存在。 将在以下时间间隔提取细胞： 将分析刺激和产生的脂质介质。 通过 将反应的变化与介质的变化进行比较 产生的，将有可能确定如何n-3脂肪酸影响 HL-60细胞的信号转导系统。

DESCRIPTION: (Adapted from Investigator's Abstract). There is increasing evidence that there are human health benefits from the consumption of omega-3 (n-3) fatty acids. These benefits include amelioration of some pathological states (cardiovascular disease and neoplastic growth) and provide an essential dietary compound required for normal growth and development in humans. While the mechanisms of these benefits are unknown it is possible that they arise from an impact of these fatty acids on intercellular signalling mechanisms that utilize lipid mediators derived from membrane phospholipids. The primary objective of this proposal is to determine the nature of the impact of n-3 fatty acids on signal transduction pathways in HL-60 cells. Undifferentiated HL-60 cells, and HL-60 cells differentiated with dimethylsulfoxide (neutrophil-like cells) and phorbol esters (macrophage-like cells) will be used.These cell models will be supplemented with oleic (n-9), arachidonic (n-6), eicosapentaenoic (n-3) and docosahexaenoic (n-3) acids. Supplemented and unsupplemented cells will be stimulated with three physiologically relevant stimuli (formylmethionylleucylphenylalanine, C5a and platelet activating factor, PAF) and three inflammatory responses examined (respiratory burst degranulation and PAF biosynthesis). In those instances where n-3 fatty acid supplementation causes changes in the response, cellular lipids will be extracted and analyzed to determine the molecular species of phospholipids present. Cells will be extracted at intervals following stimulation and the lipid mediators generated will be analyzed. By comparing alterations in the responses with alterations in the mediators generated it will be possible to determine how n-3 fatty acids affect signal transduction systems in HL-60 cells.