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10-二十烷醇通过激活猪肠上皮细胞中的 AKT(蛋白激酶 B)缓解棒曲霉素诱导的细胞周期停滞和细胞凋亡。

10-Eicosanol Alleviates Patulin-Induced Cell Cycle Arrest and Apoptosis by Activating AKT (Protein Kinase B) in Porcine Intestinal Epithelial Cells.

机构信息

Department of Animal Science and Biotechnology, Kyungpook National University, Sangju-si 37224, Gyeongsangbuk-do, Republic of Korea.

Research Institute for Innovative Animal Science, Kyungpook National University, Sangju-si 37224, Gyeongsangbuk-do, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Aug 7;25(16):8597. doi: 10.3390/ijms25168597.

Abstract

Patulin (PAT) is a fungal toxin prevalent in apples and apple products and associated with several toxic effects, potentially harming multiple organs, including the kidneys, liver, and colon. However, the precise molecular mechanism through which PAT affects the intestines remains comprehensively unclear. Therefore, this study aims to investigate the molecular effects of PAT on the intestinal epithelium. Gene expression profiling was conducted, hypothesizing that PAT induces cell cycle arrest and apoptosis through the PI3K-Akt signaling pathway. Cell cycle analysis, along with Annexin-V and propidium iodide staining, confirmed that PAT induced G2/M phase arrest and apoptosis in IPEC-J2 cells. Additionally, PAT activated the expression of cell cycle-related genes (, ) and apoptosis-related genes (, ). Treatment with SC79, an AKT activator, mitigated cell cycle arrest and apoptosis. To identify natural products that could mitigate the harmful effects of PAT in small intestinal epithelial cells in pigs, the high-throughput screening of a natural product library was conducted, revealing 10-Eicosanol as a promising candidate. In conclusion, our study demonstrates that 10-Eicosanol alleviates PAT-induced cell cycle arrest and apoptosis in IPEC-J2 cells by activating AKT.

摘要

棒曲霉素(PAT)是一种普遍存在于苹果和苹果产品中的真菌毒素,与多种毒性作用有关,可能损害多个器官,包括肾脏、肝脏和结肠。然而,PAT 影响肠道的确切分子机制尚不清楚。因此,本研究旨在研究 PAT 对肠道上皮的分子影响。进行了基因表达谱分析,假设 PAT 通过 PI3K-Akt 信号通路诱导细胞周期停滞和细胞凋亡。细胞周期分析以及 Annexin-V 和碘化丙啶染色证实,PAT 诱导 IPEC-J2 细胞 G2/M 期阻滞和细胞凋亡。此外,PAT 激活了细胞周期相关基因(、)和凋亡相关基因(、)的表达。用 AKT 激活剂 SC79 处理可减轻细胞周期阻滞和凋亡。为了鉴定可减轻猪小肠上皮细胞中 PAT 有害影响的天然产物,对天然产物文库进行了高通量筛选,发现 10-二十烷醇是一种有前途的候选物。总之,本研究表明 10-二十烷醇通过激活 AKT 缓解 PAT 诱导的 IPEC-J2 细胞的细胞周期阻滞和细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1bb/11354308/5f0830ef8a9f/ijms-25-08597-g001.jpg

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