Ursolic acid inhibiting excessive reticulophagic flux contributes to alleviate ochratoxin A-induced endoplasmic reticulum stress-and mitochondrial-mediated apoptosis  

作　　者：Huiqiong Deng Wenying Chen Lingyun Han Boyang Zhang Xun Luo Song Yao Hongwei Wang Yao Zhou Shuangchao Liu Xiao Li Shen 

机构地区：[1]School of Public Health,Zunyi Medical University,Zunyi 563000,China [2]Key Laboratory of Maternal&Child Health and Exposure Science of Guizhou Higher Education Institutes,Zunyi 563000,China [3]Chongqing Fuling District Center for Disease Control and Prevention,Chongqing 408000,China [4]Research and Development Department,Allife Medicine Inc.,Beijing 100176,China

出　　处：《Food Science and Human Wellness》2025年第4期1318-1329,共12页食品科学与人类健康(英文)

基　　金：financially supported by the National Natural Science Foundation of China(82060598,32260587);the Natural Science Foundation of Guizhou Province(QKH-J-ZK[2021]181);the Scientific Research Program of Guizhou Provincial Department of Education(QJJ[2023]019);the Science&Technology Program of Guizhou Province(QKHPTRC-CXTD[2022]014);the Excellent Youth Talents of Zunyi Medical University(17zy-006);the Innovation and Entrepreneurship Training Program for College Students of Guizhou Province(S202210661138);the Innovation and Entrepreneurship Training Program for College Students of Zunyi Medical University(ZYDC2021108)。

摘　　要：Foods and animal feeds frequently become contaminated with the nephrotoxic ochratoxin A(OTA).Our prior research has indicated that ursolic acid(UA),which is widely present in fruits and medicinal plants,has the potential to alleviate nephrotoxicity triggered by OTA.Additionally,excessive induction of endoplasmic reticulum(ER)-phagy exacerbates OTA-induced apoptosis.Therefore,further investigation is essential to comprehend whether UA can mitigate OTA-induced apoptosis by influencing ER-phagy.This objective is accomplished through a series of experiments involving assessments of cell viability,apoptosis,fluorescence microscopy,and western blot analysis.The outcomes of these experiments reveal that pre-treatment with 4μmol/L UA for 2 h can markedly reverse the elevated apoptotic rate,the co-localization of ER and lysosomes,and the protein expressions of GRP78,p-eIF2α,Chop,Bax,and Bak,as well as the reduced cell viability and the protein expressions of Lonp1,Trap1,p62,Tex264,FAM134B,Bcl-2,and Bcl-xl,all caused by exposure to 1μmol/L OTA for 24 h in human proximal tubule epithelial-originated kidney-2(HK-2)cells(P<0.05).Interestingly,the increased expression of LC3B-II induced by OTA is further amplified by UA pre-treatment(P<0.05).In conclusion,OTA triggers a harmful feedback loop between ER stress(ERS)and excessive ER-phagy,thereby further promoting ERS-and mitochondrial-mediated apoptosis in vitro.However,this effect is significantly mitigated by UA through the inhibition of autophagosome-lysosome fusion,consequently blocking the excessive ER-phagic flux.

关 键 词：Ochratoxin A Ursolic acid Endoplasmic reticulum(ER)stress ER-phagy ER-phagic flux Apoptosis 

分 类 号：R73[医药卫生—肿瘤]