文献类型：期刊文献

英文题名：Acrylamide induces intrinsic apoptosis and inhibits protective autophagy via the ROS mediated mitochondrial dysfunction pathway in U87-MG cells

作者：Deng, Linlin[1];Zhao, Mengyao[1,2];Cui, Yanan[1];Xia, Quanming[1];Jiang, Lihua[1,2];Yin, Hao[3];Zhao, Liming[1,2]

机构：[1]East China Univ Sci & Technol, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Collaborat Innovat Ctr Biomfg Technol SC, Shanghai, Peoples R China;[3]Shanghai Changzheng Hosp, Organ Transplant Ctr, Shanghai, Peoples R China

年份：2022

卷号：45

期号：6

起止页码：2601

外文期刊名：DRUG AND CHEMICAL TOXICOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000702557000001)】；

基金：This project was financially supported by the National Natural Science Foundation for Young Scientists of China [No. 31801668], the 111 Project [No. B18022], the Open Project Funding of the State Key Laboratory of Bioreactor Engineering, ECUST [ZDXM2019], the Fundamental Research Funds for the Central Universities [No. 222201814036], and the Shanghai PuJiang Program [No. 18J1401900].

语种：英文

外文关键词：Acrylamide; oxidative stress; NF-kappa B activation; intrinsic apoptosis; protective autophagy

摘要：Acrylamide (ACR) is a potential neurotoxin commonly found in the environment, as well as in food repeatedly exposed heat processing, but the mechanism underpinning ACR-induced neurotoxicity remains unclear. This study investigated the potential association and underlying signal transduction of oxidative stress, apoptosis, and autophagy associated with ACR-triggered neurotoxicity. Therefore, U87-MG cells were treated with varying ACR concentrations, while the cell activity reduction depended on the specific dosage and time parameters. Biochemical analyses showed that ACR significantly increased the reactive oxygen species (ROS), malondialdehyde (MDA), and Ca2+ levels while decreasing the glutathione (GSH) levels and mitochondrial membrane potential (Delta Psi m), finally leading to a higher cell apoptotic rate. Moreover, ACR induced U87-MG cell apoptosis and autophagy via ROS-triggered expression in the mitochondrial apoptosis pathway, NF-kappa B activation, and autophagosome accumulation. In addition, the autophagosome accumulation induced by ACR could probably be ascribed to blocked autophagic flux, inhibiting the autophagosomes from combining with lysosomes, while the inhibition of autophagy caused by ACR further promoted the initiation of apoptosis. In conclusion, the results indicated that the apoptotic and autophagic pathways responded to ACR-induced neurotoxicity. However, inhibited protective autophagy further promoted apoptotic progression. New insights may be derived from these cellular responses that can help develop diverse pathway strategies for assessing the risk posed by ACR.