Supplementary choline attenuates olive oil lipid emulsion-induced enterocyte apoptosis through suppression of CELF1/AIF pathway.
Supplementary choline attenuates olive oil lipid emulsion-induced enterocyte apoptosis through suppression of CELF1/AIF pathway.
复制标题
补充胆碱通过抑制 CELF1/AIF 通路减弱橄榄油脂肪乳诱导的肠上皮细胞凋亡
DOI：
10.1111/jcmm.13430
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发表时间：
2018-03
影响因子：
5.3
通讯作者：
Cai W
中科院分区：
文献类型：
--
作者：
Yan JK;Zhu J;Gong ZZ;Wen J;Xiao YT;Zhang T;Cai W
脂肪乳剂诱导的肠细胞凋亡是全肠外营养(TPN)支持下肠萎缩的一个重要原因，我们前期的工作表明，橄榄油脂肪乳剂(OOLE)可通过CUGBP、Elav样家族成员1(CELF1)/凋亡诱导因子(AIF)途径诱导肠细胞凋亡。由于TPN相关的并发症部分与胆碱缺乏有关，我们的目标是探讨补充胆碱是否能减轻OOLE诱导的肠细胞凋亡。在此，我们提出了补充胆碱在体内和体外对OOLE诱导的肠细胞凋亡具有保护作用的证据。在TPN大鼠模型中，在OOLE中加入补充胆碱后，细胞凋亡率显著降低，CELF1表达减少。在培养的Caco-2细胞中，补充胆碱通过抑制CELF1/AIF通路减轻OOLE诱导的细胞凋亡和线粒体功能障碍。与单纯OOLE相比，补充胆碱后CELF1和AIF的表达明显降低，而Bcl2的表达明显增加。Bax表达和caspase-3活性无明显变化。机制上，补充胆碱通过增加CELF1 mRNA的募集到加工体而抑制CELF1的表达，从而抑制其蛋白翻译。综上所述，我们的数据表明，补充胆碱对OOLE诱导的肠细胞凋亡具有有效的保护作用，因此，它有可能用于预防和治疗TPN诱导的肠萎缩。
Enterocyte apoptosis induced by lipid emulsions is a key cause of intestinal atrophy under total parenteral nutrition (TPN) support, and our previous work demonstrated that olive oil lipid emulsion (OOLE) could induce enterocyte apoptosis via CUGBP, Elav‐like family member 1 (CELF1)/ apoptosis‐inducing factor (AIF) pathway. As TPN‐associated complications are partially related to choline deficiency, we aimed to address whether choline supplementation could attenuate OOLE‐induced enterocyte apoptosis. Herein we present evidence that supplementary choline exhibits protective effect against OOLE‐induced enterocyte apoptosis both in vivo and in vitro. In a rat model of TPN, substantial reduction in apoptotic rate along with decreased expression of CELF1 was observed when supplementary choline was added to OOLE. In cultured Caco‐2 cells, supplementary choline attenuated OOLE‐induced apoptosis and mitochondria dysfunction by suppressing CELF1/AIF pathway. Compared to OOLE alone, the expression of CELF1 and AIF was significantly decreased by supplementary choline, whereas the expression of Bcl‐2 was evidently increased. No obvious alterations were observed in Bax expression and caspase‐3 activation. Mechanistically, supplementary choline repressed the expression of CELF1 by increasing the recruitment of CELF1 mRNA to processing bodies, thus resulting in suppression of its protein translation. Taken together, our data suggest that supplementary choline exhibits effective protection against OOLE‐induced enterocyte apoptosis, and thus, it has the potential to be used for the prevention and treatment of TPN‐induced intestinal atrophy.
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DOI：
10.1097/mco.0b013e3283600d46
发表时间：
2013-05
影响因子：
3.1
作者：
Mehedint MG;Zeisel SH
通讯作者：
Zeisel SH
影响因子：
2.5
作者：
Corbin KD;Zeisel SH
通讯作者：
Zeisel SH
影响因子：
4.8
作者：
Freeman, Jennifer J.;Feng, Yongjia;Teitelbaum, Daniel H.
通讯作者：
Teitelbaum, Daniel H.
影响因子：
5.5
作者：
Chung, Hee Kyoung;Rao, Jaladanki N.;Wang, Jian-Ying
通讯作者：
Wang, Jian-Ying
DOI：
10.1016/j.cbpb.2016.07.005
发表时间：
2016-12-01
影响因子：
2.2
作者：
Luo, Zhi;Wei, Chuan-Chuan;Wu, Kun
通讯作者：
Wu, Kun