title: Endoplasmic Reticulum Stress Cooperates in Zearalenone-Induced Cell Death of RAW 264.7 Macrophages.
abstract: Zearalenone (ZEA) is a fungal mycotoxin that causes cell apoptosis and necrosis. However, little is known about the molecular mechanisms of ZEA toxicity. The objective of this study was to explore the effects of ZEA on the proliferation and apoptosis of RAW 264.7 macrophages and to uncover the signaling pathway underlying the cytotoxicity of ZEA in RAW 264.7 macrophages. This study demonstrates that the endoplasmic reticulum (ER) stress pathway cooperated in ZEA-induced cell death of the RAW 264.7 macrophages. Our results show that ZEA treatment reduced the viability of RAW 264.7 macrophages in a dose- and time-dependent manner as shown by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay (MTT) and flow cytometry assay. Western blots analysis revealed that ZEA increased the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP), two ER stress-related marker genes. Furthermore, treating the cells with the ER stress inhibitors 4-phenylbutyrate (4-PBA) or knocking down CHOP, using lentivirus encoded short hairpin interfering RNAs (shRNAs), significantly diminished the ZEA-induced increases in GRP78 and CHOP, and cell death. In summary, our results suggest that ZEA induces the apoptosis and necrosis of RAW 264.7 macrophages in a dose- and time-dependent manner via the ER stress pathway in which the activation of CHOP plays a critical role.
authors: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China. cfl0604114114@163.com.
authors: Fenglei
authors: F
authors: Chen
authors: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China. liqian364@163.com.
authors: Qian
authors: Q
authors: Li
authors: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China. pipixiaoguai0118@163.com.
authors: Zhe
authors: Z
authors: Zhang
authors: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China. linpengfei@nwsuaf.edu.cn.
authors: Pengfei
authors: P
authors: Lin
authors: College of Veterinary Medicine, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China. leilanjie1988@126.com.
authors: Lanjie
authors: L
authors: Lei
authors: College of Veterinary Medicine, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China. aihuawang1966@163.com.
authors: Aihua
authors: A
authors: Wang
authors: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China. yapingjin@163.com.
authors: Yaping
authors: Y
authors: Jin
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D010654:Phenylbutyrates / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000378:metabolism; D015025:Zearalenone / Q000494:pharmacology*
chemical_list: C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D010654:Phenylbutyrates; D051742:Transcription Factor CHOP; D015025:Zearalenone; C075773:4-phenylbutyric acid
keywords: CHOP; RAW 264.7 macrophages; endoplasmic reticulum stress; zearalenone