Linoleic acid and butyrate synergize to increase Bcl-2 levels in colonocytes.

Linoleic acid and butyrate synergize to increase Bcl-2 levels in colonocytes.
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DOI:
10.1002/ijc.25323
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发表时间:
2011-01-01
影响因子:
6.4
通讯作者:
Chapkin, Robert S.
Chapkin, Robert S.
中科院分区:
医学1区
文献类型:
--
作者:
Turk, Harmony F.;Kolar, Satya S.;Fan, Yang-Yi;Cozby, Caitlin A.;Lupton, Joanne R.;Chapkin, Robert S.

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多不饱和脂肪酸(PUFA)类的生物学特性一直是许多争议的根源。例如,n-3 PUFA 具有化学保护作用,而 n-6 PUFA 可能促进肿瘤发展。由于膳食成分可能产生组合效应,因此我们进一步研究了 n-3 或 n-6 脂肪酸与不同纤维来源结合时的细胞凋亡特性。小鼠的饮食中添加了鱼油(富含 n-3 PUFA)或玉米油(富含 n-6 PUFA)以及不可发酵(纤维素)或可发酵(果胶)纤维来源。在补充实验中,用二十二碳六烯酸(DHA,22:6n-3)或亚油酸(LA,18:2n-6)(含或不含丁酸盐)处理永生化年轻成年小鼠结肠(YAMC)细胞。与所有其他饮食相比,喂食鱼油和果胶饮食的小鼠结肠细胞凋亡水平显着增加(p<0.05)。同样,DHA 和丁酸盐共同处理的 YAMC 细胞中细胞凋亡也被高度诱导。相比之下,在 YAMC 和小鼠模型中,LA/玉米油与丁酸盐/果胶处理可减少细胞凋亡并增强 bcl-2 的表达。通过使用靶向 siRNA 敲低 bcl-2,可以逆转 LA 和丁酸盐诱导的抗凋亡表型。相比之下,bcl-2 的过度表达会阻断 DHA 和丁酸盐的促凋亡作用。这些数据为膳食多不饱和脂肪酸和纤维调节细胞凋亡提供了新的机制见解。
The biological properties of polyunsaturated fatty acid (PUFA) classes have been the source of much contention. For example, n-3 PUFA are chemoprotective, while n-6 PUFA may promote tumor development. Since dietary components can have combinatorial effects, we further examined the apoptotic properties of n-3 or n-6 fatty acids when combined with different fiber sources. Mice were fed diets supplemented with either fish oil (enriched in n-3 PUFA) or corn oil (enriched in n-6 PUFA) and non-fermentable (cellulose) or fermentable (pectin) fiber sources. In complementary experiments, immortalized young adult mouse colonic (YAMC) cells were treated with docosahexaenoic acid (DHA, 22:6n-3) or linoleic acid (LA, 18:2n-6) with or without butyrate. Mice fed a fish oil and pectin diet had significantly (p<0.05) increased levels of apoptosis in colonocytes compared to all other diets. Similarly, apoptosis was highly induced in DHA and butyrate co-treated YAMC cells. In contrast, in both YAMC and mouse models, LA/corn oil with butyrate/pectin treatment reduced apoptosis and enhanced expression of bcl-2. The LA and butyrate induced anti-apoptotic phenotype was reversed by knocking down bcl-2 using targeted siRNA. In comparison, overexpression of bcl-2 blocked the pro-apoptotic effect of DHA and butyrate. These data provide new mechanistic insights into the regulation of apoptosis by dietary PUFA and fiber.
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