Tang Li, Zeng Zihan, Zhou Yuanhao, Wang Baikui, Zou Peng, Wang Qi, Ying Jiafu, Wang Fei, Li Xiang, Xu Shujie, Zhao Pengwei, Li Weifen
Key Laboratory of Molecular Animal Nutrition of the Ministry of Education, Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou 310058, China.
Antioxidants (Basel). 2021 Sep 28;10(10):1545. doi: 10.3390/antiox10101545.
Autophagy is a conserved proteolytic mechanism, which degrades and recycles damaged organs and proteins in cells to resist external stress. Probiotics could induce autophagy; however, its underlying molecular mechanisms remain elusive. Our previous study has found that could alleviate oxidative stress by inducing autophagy in rats. This research aimed to verify whether can induce autophagy to alleviate oxidative stress in IPEC-J2 cells, as well as explore its mechanisms. IPEC-J2 cells were first pretreated with 10 CFU/mL , and then were induced to oxidative stress by the optimal dose of diquat. The results showed that significantly triggered autophagy, indicated by the up-regulation of LC3 and Beclin1 along with downregulation of p62 in IPEC-J2 cells. Further analysis revealed that inhibited the AKT-FOXO signaling pathway by inhibiting the expression of p-AKT and p-FOXO and inducing the expression of SIRT1, resulting in increasing the transcriptional activity of FOXO3 and gene expression of the ATG5-ATG12 complex to induce autophagy, which alleviated oxidative stress and apoptosis. Taken together, can induce AKT-FOXO-mediated autophagy to alleviate oxidative stress-induced apoptosis and cell damage, thus providing novel theoretical support for probiotics in the prevention and treatment of oxidative damage.
自噬是一种保守的蛋白水解机制，可降解和回收细胞内受损的细胞器和蛋白质以抵抗外部压力。益生菌可诱导自噬；然而，其潜在的分子机制仍不清楚。我们之前的研究发现，[具体物质]可通过诱导大鼠自噬来减轻氧化应激。本研究旨在验证[具体物质]是否能诱导IPEC-J2细胞自噬以减轻氧化应激，并探究其机制。IPEC-J2细胞先用10 CFU/mL[具体物质]预处理，然后用最佳剂量的敌草快诱导氧化应激。结果表明，[具体物质]显著触发了自噬，IPEC-J2细胞中LC3和Beclin1上调以及p62下调表明了这一点。进一步分析显示，[具体物质]通过抑制p-AKT和p-FOXO的表达并诱导SIRT1的表达来抑制AKT-FOXO信号通路，导致FOXO3转录活性增加以及ATG5-ATG12复合体基因表达增加以诱导自噬，从而减轻氧化应激和细胞凋亡。综上所述，[具体物质]可诱导AKT-FOXO介导的自噬以减轻氧化应激诱导的细胞凋亡和细胞损伤，从而为益生菌在预防和治疗氧化损伤方面提供新的理论支持。
