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.

中文翻译：

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PERK-CHOP途径参与伏马毒素B1诱导的人胃上皮细胞的细胞毒性。

伏马菌素B1（FB1）是一种真菌毒素，由轮状镰刀菌（Fusarium v​​erticillioides）和枯萎镰刀菌（Fusarium proliferatum）产生，是全球玉米的常见真菌污染物。其作为天然毒素的潜在健康危害已在人类和家畜中得到了充分证明。但是，尚未阐明导致FB1诱导细胞毒性的分子机制和关键因素。在这项研究中，我们首先检查了由FB1诱导的人胃上皮细胞系（GES-1）的细胞毒性。我们发现FB1明显降低了细胞活力，并诱导了凋亡细胞的死亡。此外，暴露于FB1后，ER应激标志物的水平显着增加，并且ER应激抑制剂4-苯基丁酸强烈抑制了FB1诱导的细胞毒性。有趣的是，GSK2606414或shPERK3对PERK活性的抑制作用阻止了FB1诱导的凋亡和细胞增殖的抑制，这表明FB1诱导的细胞毒性取决于该信号通路。此外，myriocin可以缓解FB1诱导的ER应激并防止细胞死亡，这暗示鞘脂代谢的破坏是FB1诱导的细胞毒性的顶峰事件。在本研究中，我们证明了与ER应激相关的PERK-CHOP信号通路是FB1诱导的细胞毒性的一种新机制，将来应关注由FB1引起的胃肠道损伤。这暗示鞘脂代谢的破坏是FB1诱导的细胞毒性的顶峰事件。在本研究中，我们证明了与ER应激相关的PERK-CHOP信号通路是FB1诱导的细胞毒性的一种新机制，将来应关注由FB1引起的胃肠道损伤。这暗示鞘脂代谢的破坏是FB1诱导的细胞毒性的顶峰事件。在本研究中，我们证明了与ER应激相关的PERK-CHOP信号通路是FB1诱导的细胞毒性的一种新机制，将来应关注由FB1引起的胃肠道损伤。