未折叠蛋白反应
内质网
ATF6
细胞凋亡
XBP1型
细胞生物学
展青霉素
程序性细胞死亡
生物
线粒体
线粒体ROS
内质网相关蛋白降解
化学
生物化学
真菌毒素
RNA剪接
核糖核酸
植物
基因
作者
Manel Boussabbeh,Intidhar Ben Salem,Alexandre Prola,Arnaud Guilbert,Hassen Bacha,Christophe Lemaire
标识
DOI:10.1093/toxsci/kfu319
摘要
Patulin (PAT) is a toxic metabolite produced by several filamentous fungi of the genera of Penicillium, Aspergillus, and Byssochlamys. PAT is the most common mycotoxin found in apples and apple-based products including juice, compotes, cider, and baby food. Exposure to this mycotoxin has been reported to induce intestinal and kidney injuries. This study investigated the mechanism of PAT-induced toxicity in human colon carcinoma (HCT116) and embryonic kidney cells (HEK293). We demonstrated that PAT activated endoplasmic reticulum (ER) and unfolded protein response as evidenced by up-regulation of GRP78 and GADD34, splicing of XBP1 mRNA, and expression of the proapoptotic factor CHOP. This ER stress response was accompanied by the induction of the mitochondrial apoptotic pathway. Apoptosis occurred with ROS production, drop in mitochondrial membrane potential and caspase activation. Further, we showed that deficiency of the proapoptotic protein Bax or Bak protected cells against PAT-induced apoptosis. The treatment of cells with the ROS scavenger N-acetyl cysteine inhibits the ER stress response and prevents mitochondrial apoptosis. Collectively, our data provide new mechanistic insights in the signaling pathways of the cell death induced by PAT and demonstrate that PAT induces cytotoxicity through a ROS-dependent mechanism involving ER stress and activation of mitochondrial apoptotic pathway in human intestinal and kidney cells.
科研通智能强力驱动
Strongly Powered by AbleSci AI