Chapkin Robert S, Seo Jeongmin, McMurray David N, Lupton Joanne R
Center for Environmental and Rural Health, Texas A&M University, College Station, TX 77843-2553, United States.
Chem Phys Lipids. 2008 May;153(1):14-23. doi: 10.1016/j.chemphyslip.2008.02.011. Epub 2008 Mar 4.
A growing body of epidemiological, clinical, and experimental evidence has underscored both the pharmacological potential and the nutritional value of dietary fish oil enriched in very long chain n-3 PUFAs such as docosahexaenoic acid (DHA, 22:6, n-3) and eicosapentaenoic acid (EPA, 20:5, n-3). The broad health benefits of very long chain n-3 PUFAs and the pleiotropic effects of dietary fish oil and DHA have been proposed to involve alterations in membrane structure and function, eicosanoid metabolism, gene expression and the formation of lipid peroxidation products, although a comprehensive understanding of the mechanisms of action has yet to be elucidated. In this review, we present data demonstrating that DHA selectively modulates the subcellular localization of lipidated signaling proteins depending on their transport pathway, which may be universally applied to other lipidated protein trafficking. An interesting possibility raised by the current observations is that lipidated proteins may exhibit different subcellular distribution profiles in various tissues, which contain a distinct membrane lipid composition. In addition, the current findings clearly indicate that subcellular localization of proteins with a certain trafficking pathway can be subjected to selective regulation by dietary manipulation. This form of regulated plasma membrane targeting of a select subset of upstream signaling proteins may provide cells with the flexibility to coordinate the arrangement of signaling translators on the cell surface. Ultimately, this may allow organ systems such as the colon to optimally decode, respond, and adapt to the vagaries of an ever-changing extracellular environment.
越来越多的流行病学、临床和实验证据强调了富含超长链n-3多不饱和脂肪酸（如二十二碳六烯酸（DHA，22:6，n-3）和二十碳五烯酸（EPA，20:5，n-3））的膳食鱼油的药理潜力和营养价值。超长链n-3多不饱和脂肪酸的广泛健康益处以及膳食鱼油和DHA的多效性作用被认为涉及膜结构和功能的改变、类花生酸代谢、基因表达以及脂质过氧化产物的形成，尽管对其作用机制的全面理解还有待阐明。在本综述中，我们展示的数据表明，DHA根据其转运途径选择性地调节脂化信号蛋白的亚细胞定位，这可能普遍适用于其他脂化蛋白的运输。当前观察结果提出的一个有趣可能性是，脂化蛋白在含有不同膜脂质组成的各种组织中可能表现出不同的亚细胞分布模式。此外，目前的研究结果清楚地表明，具有特定运输途径的蛋白质的亚细胞定位可以通过饮食调控进行选择性调节。这种对特定上游信号蛋白子集的调节性质膜靶向形式可能为细胞提供灵活性，以协调细胞表面信号转导分子的排列。最终，这可能使诸如结肠等器官系统能够最佳地解码、响应并适应不断变化的细胞外环境的变幻莫测。
