1. Academic Validation
  2. Ochratoxin A induces cytotoxicity through ROS-mediated endoplasmic reticulum stress pathway in human gastric epithelium cells

Ochratoxin A induces cytotoxicity through ROS-mediated endoplasmic reticulum stress pathway in human gastric epithelium cells

  • Toxicology. 2022 Sep;479:153309. doi: 10.1016/j.tox.2022.153309.
Yuan Wang 1 Jinfeng Cui 1 Guona Zheng 2 Man Zhao 3 Zengfang Hao 1 Hongguang Lian 1 Yuehong Li 1 Wenxin Wu 1 Xianghong Zhang 4 Juan Wang 5
Affiliations

Affiliations

  • 1 Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, China.
  • 2 Department of Pathology, Heibei General Hospital, Shijiazhuang, China.
  • 3 Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China.
  • 4 Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, China; Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China.
  • 5 Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, China. Electronic address: sjzwangjuan@126.com.
Abstract

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium species that greatly threatens human health. We previously showed that OTA induced cycle arrest, Apoptosis and Autophagy in human gastric epithelium cells (GES-1). However, the mechanism underlying these effects is still unclear. Here, we showed that OTA exposure increased the expression of endoplasmic reticulum (ER) stress indicators (GRP78, PERK, ATF6, eIF2α, and CHOP), suggesting the activation of the unfolded protein response pathway. 4-phenylbutyric acid (4-PBA), an ER stress-specific inhibitor, attenuated OTA-induced loss of cell viability and Apoptosis in GES-1 cells. It also attenuated the G2 phase arrest and Autophagy induced by OTA, as evidenced by upregulated G2 phase-related proteins (Cdc2, Cdc25C, and cyclinB1) and downregulated Autophagy markers (LC3B and Beclin-1). Moreover, OTA was found to increase ROS generation, and the inhibition of ROS formation by N-acetylcysteine (NAC), an ROS inhibitor, attenuated OTA-induced ER stress and subsequent Apoptosis, cell cycle arrest, and Autophagy. Collectively, these results suggest that the ROS-mediated ER stress pathway contributes to the OTA toxin-induced cytotoxicity in GES-1 cells. This study offers new insights into the molecular mechanisms underlying OTA toxicity in gastric cells.

Keywords

Apoptosis; Autophagy; Cell cycle arrest; Endoplasmic reticulum stress; Ochratoxin A; ROS.

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