Paraoxonase 2 modulates a proapoptotic function in LS174T cells in response to quorum sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone.
Paraoxonase 2 modulates a proapoptotic function in LS174T cells in response to quorum sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone.
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对氧磷酶 2 响应群体感应分子 N-(3-氧代十二酰基)-L-高丝氨酸内酯调节 LS174T 细胞中的促凋亡功能
DOI：
10.1038/srep28778
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发表时间：
2016-07-01
影响因子：
4.6
通讯作者：
Zhao R
中科院分区：
文献类型：
--
作者：
Tao S;Luo Y;Bin He;Liu J;Qian X;Ni Y;Zhao R
粘液层覆盖在胃肠道，是肠道抵御感染的第一道防线。肠道革兰氏阴性菌产生的N-酰基-高丝氨酸内酯(AHL)群体感应分子可影响肠上皮细胞的动态平衡。在这项研究中，我们研究了两种具有代表性的长链和短链AHL，N-3-氧代十二烷基高丝氨酸内酯(C12-HSL)和N-丁酰高丝氨酸内酯(C4-HSL)对LS174T细胞活力和粘液分泌的影响。C12-HSL而不是C4-HSL通过诱导线粒体功能障碍和激活细胞凋亡而导致粘蛋白表达减少，从而显着降低细胞存活率。脂质筏干扰剂(甲基-β-环糊精，M-βCD)和氧化应激抑制剂(N-乙酰-L-半胱氨酸，N-乙酰半胱氨酸，N-乙酰-HSL-半胱氨酸，NAC)对C12-HSL损伤细胞的活力有轻微的恢复作用，而对氧磷酶2(PON2)抑制剂(三氮唑并[4，3-a]喹诺酮，TQ416)对细胞活力和粘蛋白分泌有显著影响。当C12-HSL和TQ416同时作用于LS174T细胞时，TQ416对细胞活力的正向作用最大。然而，如果先用C12-HSL处理细胞40 分钟，然后再加入TQ46，TQ416对细胞活力没有影响。这些结果表明，C12-HSL-酸过程在早期激活细胞凋亡，这是C12-HSL对肠粘液屏障功能影响的一部分。
A mucus layer coats the gastrointestinal tract and serves as the first line of intestinal defense against infection. N-acyl-homoserine lactone (AHL) quorum-sensing molecules produced by gram-negative bacteria in the gut can influence the homeostasis of intestinal epithelium. In this study, we investigated the effects of two representative long- and short-chain AHLs, N-3-(oxododecanoyl)-homoserine lactone (C12-HSL) and N-butyryl homoserine lactone (C4-HSL), on cell viability and mucus secretion in LS174T cells. C12-HSL but not C4-HSL significantly decreased cell viability by inducing mitochondrial dysfunction and activating cell apoptosis which led to a decrease in mucin expression. Pretreatment with lipid raft disruptor (Methyl-β-cyclodextrin, MβCD) and oxidative stress inhibitor (N-acetyl-L-cysteine, NAC) slightly rescued the viability of cells damaged by C12-HSL exposure, while the paraoxonase 2 (PON2) inhibitor (Triazolo[4,3-a]quinolone, TQ416) significantly affected recovering cells viability and mucin secretion. When LS174T cells were treated with C12-HSL and TQ416 simultaneously, TQ416 showed the maximal positive effect on cells viability. However, if cells were first treated with C12-HSL for 40 mins, and then TQ46 was added, the TQ416 had no effect on cell viability. These results suggest that the C12-HSL-acid process acts at an early step to activate apoptosis as part of C12-HSL’s effect on intestinal mucus barrier function.