1. Academic Validation
  2. Involvement of PERK-CHOP pathway in fumonisin B1- induced cytotoxicity in human gastric epithelial cells

Involvement of PERK-CHOP pathway in fumonisin B1- induced cytotoxicity in human gastric epithelial cells

  • Food Chem Toxicol. 2020 Feb;136:111080. doi: 10.1016/j.fct.2019.111080.
Song Yu 1 Bingxuan Jia 1 Yunxia Yang 1 Na Liu 1 Aibo Wu 2
Affiliations

Affiliations

  • 1 SIBS-UGENT-SJTU Joint Laboratory of Mycotoxin Research, CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, PR China.
  • 2 SIBS-UGENT-SJTU Joint Laboratory of Mycotoxin Research, CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, PR China. Electronic address: abwu@sibs.ac.cn.
Abstract

Fumonisin B1 (FB1) is a mycotoxin, produced by Fusarium verticillioides and Fusarium proliferatum, and a common Fungal contaminant of maize worldwide. Its potential health hazard as a natural toxin is well documented in human and domestic Animals. However, the molecular mechanism and the key factors responsible for FB1-induced cytotoxicity have not been elucidated. In this study, we first examined the cytotoxicity induced by FB1 in human gastric epithelial cell line (GES-1). We found that FB1 notably decreased cell viability and induced apoptotic cell death. Furthermore, the levels of ER stress markers were significantly increased after FB1 exposure and the ER stress inhibitor 4-phenylbutyric acid strongly suppressed FB1-induced cytotoxicity. Interestingly, the inhibition of PERK activity by GSK2606414 or shPERK3 blocked FB1-induced apoptotic cell death and cell proliferation suppression, which indicated that the cytotoxicity induced by FB1 was dependent on this signalling pathway. Moreover, myriocin could relieve FB1-induced ER stress and prevent cell death, which implied that the disruption of sphingolipid metabolism is an apical event for FB1-induced cytotoxicity. In the present study, we demonstrated that the ER stress-related PERK-CHOP signalling pathway is a novel mechanism for FB1-induced cytotoxicity and the gastrointestinal injury caused by FB1 should be concerned in the future.

Keywords

Apoptosis; ER stress; Flow cytometry; Fumonisin B1; GES-1 cells; PERK-CHOP pathway.

Figures
Products