2. Academic Validation
  3. Analysis of the roles of the Notch1 signalling pathway in modulating deoxynivalenol cytotoxicity

Analysis of the roles of the Notch1 signalling pathway in modulating deoxynivalenol cytotoxicity

  • Ecotoxicol Environ Saf. 2022 Oct 19;246:114183. doi: 10.1016/j.ecoenv.2022.114183.
Yeyi Xiao 1,  Jie Wang 2,  Jingneng Wang 3,  Haifei Wang 4,  Shenglong Wu 5,  Wenbin Bao 6
Affiliations

Affiliations

  • 1 Key Laboratory for Animal Genetic, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. Electronic address: yeyixiao@126.com.
  • 2 Key Laboratory for Animal Genetic, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. Electronic address: wangjie4228@163.com.
  • 3 Shanghai Xiongtu Biotechnology Co., Ltd., Shanghai 200000, China. Electronic address: xtswsh@163.com.
  • 4 Key Laboratory for Animal Genetic, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. Electronic address: wanghaiffei@126.com.
  • 5 Key Laboratory for Animal Genetic, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. Electronic address: slwu@yzu.edu.cn.
  • 6 Key Laboratory for Animal Genetic, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; Shanghai Xiongtu Biotechnology Co., Ltd., Shanghai 200000, China. Electronic address: wbbao@yzu.edu.cn.
PMID: 36270035 DOI: 10.1016/j.ecoenv.2022.114183
Abstract

Deoxynivalenol (DON) is a trichothecenes produced by fungi that is widespread and poses a threat to human and animal health. The Notch1 signalling pathway is tightly involved in cell fate determination. The aim of this study was to investigate the role of the Notch1 signalling pathway in DON exposure. Herein, we found that the Notch1 signalling pathway was significantly activated after DON exposure, while Notch1 expression was negatively regulated by DON-induced ROS. Then, the Notch1 signalling pathway was blocked by the γ-secretase Inhibitor DAPT in DON exposure. Flow cytometry analysis and antioxidant parameter measurements revealed that DAPT treatment significantly aggravated the oxidative stress induced by DON. The detection of Apoptosis showed that DAPT treatment increased the cell apoptotic rate. Further analysis revealed that inhibiting the Notch1 signalling pathway reduced Autophagy upon DON exposure. RT-qPCR and Western blot analysis showed that inhibiting the Notch1 signalling pathway aggravated cellular inflammation and activated the MAPK pathway, indicating that the MAPK pathway may be the downstream signalling pathway. Taken together, our research revealed that the Notch1 signalling pathway is essential for protection against DON. Inhibition of Notch1 signalling increases oxidative stress, causes cell Apoptosis, reduces Autophagy and aggravates cell inflammation after DON exposure. This study investigated the role of the Notch1 signalling pathway in DON exposure and provided a basis for exploring the mechanism of DON.

Keywords

Deoxynivalenol; MAPK; Notch1; Oxidative damage; Toxicity.

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