Docosahexaenoic acid alters the size and distribution of cell surface microdomains
Docosahexaenoic acid alters the size and distribution of cell surface microdomains
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DOI：
10.1016/j.bbamem.2007.11.003
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发表时间：
2008-02-01
影响因子：
3.4
通讯作者：
Prior, Ian A.
中科院分区：
文献类型：
--
作者：
Chapkin, Robert S.;Wang, Naisyin;Prior, Ian A.
我们最近产生的营养数据表明，化学保护性膳食n-3多不饱和脂肪酸(n-3 PUFA)能够在体内取代脂筏微域中的酰化蛋白质[D.W.Ma，J.Seo，L.A.Davidson，E.S.Callaway，Y.Y.fan，J.R.Lupton，R.S.Chapkin，n-3PUFA Alter Caveolae Lapeolae Alter Caveolae and Resident Protein in小鼠结肠，FASEB J.18(2004)1040-1042；范永元，L.H.Ly R.Barhoumi，D.N.McMurray，R.S.Chapkin，膳食二十二碳六烯酸抑制T细胞蛋白激酶CO脂筏募集和IL-2募集，J.173(2004)6151-6160]。饮食中超长链n-3多不饱和脂肪酸的主要来源来自富含二十二碳六烯酸(DHA，22：6N-3)的鱼类。在这项研究中，我们试图确定DHA对细胞表面微域组织的影响。使用质膜的免疫金电子显微镜结合验证微域标记的空间点分析，在HeLa细胞中以高分辨率显示了没有形态特征的微域。胆固醇依赖(GFP-TH)和胆固醇非依赖(GFP-TK)纳米簇内的探针聚集对n-3PUFA处理细胞具有不同的敏感性。对GFP-TH(5 mN金)的单变量K函数分析表明，与对照脂肪酸相比，DHA和亚油酸(LA，18：2(Delta 9，12))的预处理显著增加了GFP-TH的聚集度(p<；0.05)，而LA显著降低了GFP-TK的聚集度(p<；0.05)。这些新的数据表明，PUFA-eDrichment从根本上改变了内叶的质膜组织。我们推测，我们的发现可能有助于定义一种新的范式，以更好地理解信令网络中n-3PUFA调制的复杂性。(C)2007 Elsevier B.V.保留所有权利。
We recently generated nutritional data suggesting that chemoprotective dietary n-3 polyunsaturated fatty acids (n-3 PUFA) are capable of displacing acylated proteins from lipid raft microdomains in vivo [D.W. Ma, J. Seo, L.A. Davidson, E.S. Callaway, Y.Y. Fan, J.R. Lupton, R.S. Chapkin, n-3 PUFA alter caveolae lipid composition and resident protein localization in mouse colon, FASEB J. 18 (2004) 1040-1042; Y.Y. Fan, L.H. Ly R. Barhoumi, D.N. McMurray, R.S. Chapkin, Dietary docosahexaenoic acid suppresses T cell protein kinase CO lipid raft recruitment and IL-2 recruitment, J. Immunol. 173 (2004) 6151-6160]. A primary source of very long chain n-3 PUFA in the diet is derived from fish enriched with docosahexaenoic acid (DHA, 22:6n-3). In this study, we sought to determine the effect of DHA on cell surface microdomain organization in situ. Using immuno-gold electron microscopy of plasma membrane sheets coupled with spatial point analysis of validated microdomain markers, morphologically featureless microdomains were visualized in HeLa cells at high resolution. Clustering of probes within cholesterol-dependent (GFP-tH) versus cholesterol-independent (GFP-tK) nanoclusters was differentially sensitive to n-3 PUFA treatment of cells. Univariate K-function analysis of GFP-tH (5 mn gold) revealed a significant increase in clustering (p < 0.05) by pre-treatment with DHA and linoleic acid (LA, 18:2(Delta 9,12)) compared to control fatty acids; whereas LA significantly (p < 0.05) reduced GFP-tK clustering. These novel data suggest that the plasma membrane organization of inner leaflets is fundamentally altered by PUFA-eDrichment. We speculate that our findings may help define a new paradigm to better understand the complexity of n-3 PUFA modulation of signaling networks. (c) 2007 Elsevier B.V. All rights reserved.