ReferenceID 5222

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

Food Chem Toxicol

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

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Reference Id
5222
Evidence Id
21812
Core Evidence Id
21812
Source Reference Id
3718
Herb2 Reference Id
HBREF004515
Subject Paper Key
HBIN026409_31891755
Pubmed Id
31891755
Doi
10.1016/j.fct.2019.111080
Paper Title
Involvement of PERK-CHOP pathway in fumonisin B1- induced cytotoxicity in human gastric epithelial cells
Paper 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.
Journal
Food Chem Toxicol
Publish Year
2020
Experiment Subject
human; human gastric epithelial cell line; maize
Experiment Type
Cell Experiment
Phenotype Related
Gastrointestinal Injury
Paper Title Cn
Paper Title En
Involvement of PERK-CHOP pathway in fumonisin B1- induced cytotoxicity in human gastric epithelial cells
Bilingual Status
semi_complete