Dietary n-3 PUFA alter colonocyte mitochondrial membrane composition and function
Dietary n-3 PUFA alter colonocyte mitochondrial membrane composition and function
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DOI：
10.1007/s11745-002-0880-8
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发表时间：
2002-02-01
期刊：
影响因子：
1.9
通讯作者：
Lupton, JR
中科院分区：
文献类型：
--
作者：
Chapkin, RS;Hong, MY;Lupton, JR
有实验证据表明，膳食鱼油含有 n-3 脂肪酸家族，即 EPA 和 DHA，可以部分通过增加细胞凋亡来防止结肠肿瘤的发展。由于线粒体可以充当细胞凋亡的中央执行者，我们假设 EPA 和 DHA 掺入结肠细胞线粒体膜（由于其高度不饱和度）将增强对氧化磷酸化产生的活性氧 (ROS) 损伤的敏感性。反过来，这会损害线粒体功能，从而引发细胞凋亡。为了检验这一假设，从喂食鱼油、纯化的 n-3 脂肪酸乙酯或玉米油（对照）的大鼠中分离出结肠隐窝。膳食脂质来源对结肠线粒体磷脂类摩尔百分比没有影响，尽管 EPA 和 DHA 的掺入与已知可促进结肠肿瘤发展的 n-6 脂肪酸（即亚油酸 ULNA）及其代谢产物花生四烯酸（ARA）的减少有关。通过共聚焦显微镜评估，主要磷脂库中的选择成分变化与线粒体功能的变化相关。心磷脂中 LNA 加 ARA 的 mol% 总和与 ROS 呈负相关 (P = 0.024)。乙醇胺甘油磷脂ARA W = 0.046)和胆碱甘油磷脂LNA (P = 0.033)水平与线粒体膜电位呈正相关。相反，乙醇胺甘油磷脂中的EPA (P = 0.042)和DHA (P = 0.024)水平与线粒体膜电位呈负相关，此外，胆碱甘油磷脂中的EPA和DHA水平(P = 0.026)与caspase 3活性呈正相关。这些数据提供了体内证据，表明饮食中的 EPA 和 DHA 会诱导结肠线粒体膜磷脂的成分变化，从而促进细胞凋亡。
There is experimental evidence that dietary fish oil, which contains the n-3 fatty acid family, i.e., EPA and DHA, protects against colon tumor development, in part by increasing apoptosis. Since mitochondria can act as central executioners of apoptosis, we hypothesized that EPA and DHA incorporation into colonocyte mitochondrial membranes, owing to their high degree of unsaturation, would enhance susceptibility to damage by reactive oxygen species (ROS) generated via oxidative phosphorylation. This, in turn, would compromise mitochondrial function, thereby initiating apoptosis. To test this hypothesis, colonic crypts were isolated from rats fed either fish oil, purified n-3 fatty acid ethyl esters, or corn oil (control). Dietary lipid source had no effect on colonic mitochondrial phospholipid class mole percentages, although incorporation of EPA and DHA was associated with a reduction in n-6 fatty acids known to enhance colon tumor development, i.e., linoleic acid ULNA) and its metabolic product, arachidonic acid (ARA). Select compositional changes in major phospholipid pools were correlated to alterations in mitochondrial function as assessed by confocal microscopy. The mol% sum of LNA plus ARA in cardiolipin was inversely correlated with ROS (P = 0.024). Ethanolamine glycerophospholipid ARA W = 0.046) and choline glycerophospholipid LNA (P = 0.033) levels were positively correlated to mitochondrial membrane potential. In contrast, ethanolamine glycerophospholipid EPA (P = 0.042) and DHA (P = 0.024) levels were negatively correlated to mitochondrial membrane potential, Additionally, EPA and DHA levels in choline glycerophospholipids (P = 0.026) were positively correlated with caspase 3 activity. These data provide evidence in vivo indicating that dietary EPA and DHA induce compositional changes in colonic mitochondrial membrane phospholipids that facilitate apoptosis.