期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 136, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2019.111080
关键词
Fumonisin B1; Apoptosis; ER stress; PERK-CHOP pathway; GES-1 cells; Flow cytometry
资金
- National Key Research and Development Program of China [2017YFC1600304]
- MOST [2016YFE0112900, 201513006-02-3]
- National Natural Science Foundation of China [31772087]
- Shanghai Agriculture Applied Technology Development Program, China [2019-02-08-00-02-F01145]
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 FE1-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.
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