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糖尿病及内分泌病学学术中心

自噬可通过IKK信号通路减轻氧化应激来保护肠上皮细胞免受Deoxynivalenol毒性

Autophagy protects intestinal epithelial Cells against Deoxynivalenol toxicity by alleviating oxidative stress via IKK signaling pathway

来源:Scopus 发布时间:2015-11-27
作者:Tang, Y. , Li, J., Li, F. , Hu, C.-A.A., Liao, P., Tan, K., Tan, B., Xiong, X., Liu, G., Li, T., Yin, Y.
机构: 动物营养与饲料科学农业部中国科学院中南地区观察和实验站 动物与家禽科学湖南工程和研究中心 畜禽健康喂养研究中心 亚热带农业研究所 亚热带农业生态学和甲功重点实验室
期刊: FREE RADICAL BIO MED 2015年12月期89卷

Autophagy is an intracellular process of homeostatic degradation that promotes cell survival under various stressors. Deoxynivalenol (DON), a fungal toxin, often causes diarrhea and disturbs the homeostasis of the intestinal system. To investigate the function of intestinal autophagy in response to DON and associated mechanisms, we firstly knocked out ATG5 (autophagy-related gene 5) in porcine intestinal epithelial cells (IPEC-J2) using CRISPR-Cas9 technology. When treated with DON, autophagy was induced in IPEC-J2 cells but not in IPEC-J2.Atg5ko cells. The deficiency in autophagy increased DON-induced apoptosis in IPEC-J2.atg5ko cells, in part, through the generation of reactive oxygen species (ROS). The cellular stress response can be restored in IPEC-J2.atg5ko cells by overexpressing proteins involved in protein folding. Interestingly, we found that autophagy deficiency downregulated the expression of endoplasmic reticulum folding proteins BiP and PDI when IPEC-J2.atg5ko cells were treated with DON. In addition, we investigated the molecular mechanism of autophagy involved in the IKK, AMPK, and mTOR signaling pathway and found that Bay-117082 and Compound C, specific inhibitors for IKK and AMPK, respectively, inhibited the induction of autophagy. Taken together, our results suggest that autophagy is pivotal for protection against DON in pig intestinal cells. © 2015 Elsevier Inc.

 

通讯作者:Key Laboratory of Agroecology and Processing of Subtropical Region, Institute of Subtropical Agriculture, Research Center for Healthy Breeding of Livestock and Poultry, Hunan Engineering and Research Center for Animal and Poultry Science, Sci. Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central China, Chinese Academy of Science, Ministry of Agriculture, Changsha City, Hunan, China
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