Ding Jiayi, Cheng Xinyi, Zeng Chun, Zhao Qintao, Xing Chenghong, Zhang Caiying, Cao Huabin, Guo Xiaoquan, Hu Guoliang, Zhuang Yu
Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang, Jiangxi 330045, P. R. China.
J Agric Food Chem. 2024 Dec 18;72(50):28093-28108. doi: 10.1021/acs.jafc.4c05876. Epub 2024 Dec 4.
Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins in food and feed, seriously jeopardizing the intestinal health, while the effects of AFB1 on intestinal damage remain to be well understood. This study aims to evaluate the effect of AFB1 on intestinal injury by regulating AMP-activated protein kinase (AMPK)-mediated pyroptosis . The present study showed that AFB1 led to the formation of large number of bubble-like protrusions on the cell membrane, releasing lactate dehydrogenase (LDH) and interleukin-1β (IL-1β). Stimulation with AFB1 resulted in the activation of the NOD-like receptor protein 3 (NLRP3) pathway, as indicated by the increased expression of pyroptosis-associated factor mRNAs and proteins, which ultimately led to a significant upregulation of the pyroptosis rate. Meanwhile, AFB1 caused dysfunction of mitochondrial dynamics by activating the AMPK signaling pathway as mainly evidenced by upregulating dynamin-1-like protein 1 (Drp1) mRNA and protein expression. Moreover, inhibition of NLRP3 and AMPK pathways by MCC950 and compound C, respectively, significantly alleviated AFB1-induced damage in IPEC-J2 cells, evidenced by suppressed NLRP3-mediated pyroptosis, and ameliorated AMPK-mediated mitochondrial dynamics imbalance. In conclusion, these results demonstrated that AFB1 promoted pyroptosis of IPEC-J2 cells by interfering with mitochondrial dynamics by activating the AMPK/NRLP3 pathway.
黄曲霉毒素B1（AFB1）是食品和饲料中毒性最强的霉菌毒素之一，严重危害肠道健康，而AFB1对肠道损伤的影响仍有待深入了解。本研究旨在通过调节AMP激活的蛋白激酶（AMPK）介导的细胞焦亡来评估AFB1对肠道损伤的影响。本研究表明，AFB1导致细胞膜上形成大量气泡样突起，释放乳酸脱氢酶（LDH）和白细胞介素-1β（IL-1β）。AFB1刺激导致NOD样受体蛋白3（NLRP3）通路激活，表现为细胞焦亡相关因子mRNA和蛋白表达增加，最终导致细胞焦亡率显著上调。同时，AFB1通过激活AMPK信号通路导致线粒体动力学功能障碍，主要表现为上调发动蛋白样蛋白1（Drp1）mRNA和蛋白表达。此外，分别用MCC950和化合物C抑制NLRP3和AMPK通路，显著减轻了AFB1诱导的IPEC-J2细胞损伤，表现为NLRP3介导的细胞焦亡受到抑制，AMPK介导的线粒体动力学失衡得到改善。总之，这些结果表明，AFB1通过激活AMPK/NRLP3通路干扰线粒体动力学，促进IPEC-J2细胞焦亡。
