1. Academic Validation
  2. Excessive ER-phagy contributes to ochratoxin A-induced apoptosis

Excessive ER-phagy contributes to ochratoxin A-induced apoptosis

  • Food Chem Toxicol. 2023 Apr 18;176:113793. doi: 10.1016/j.fct.2023.113793.
Huiqiong Deng 1 Wenying Chen 1 Boyang Zhang 2 Yiwen Zhang 1 Lingyun Han 1 Qipeng Zhang 3 Song Yao 1 Hongwei Wang 1 Xiao Li Shen 4
Affiliations

Affiliations

  • 1 School of Public Health, Zunyi Medical University, Zunyi, 563000, Guizhou, PR China.
  • 2 Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, PR China.
  • 3 School of Public Health, Zunyi Medical University, Zunyi, 563000, Guizhou, PR China; Depatment of Hospital Infection Control, The Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, PR China.
  • 4 School of Public Health, Zunyi Medical University, Zunyi, 563000, Guizhou, PR China. Electronic address: xiaolishen1983@163.com.
Abstract

The nephrotoxic secondary Fungal metabolite ochratoxin A (OTA) is ubiquitously existed in foodstuffs and feeds. Although our earlier research provided preliminary evidence that endoplasmic reticulum (ER) was crucial in OTA-induced nephrotoxicity, more research is necessary to understand the fine-tune mechanisms involving ER stress (ERS), ER-phagy, and Apoptosis. In the present study, the cell viability and protein expressions of human proximal tubule epithelial (HK-2) cells in response to OTA and/or chloroquine/rapamycin/sodium phenylbutyrate/tunicamycin were determined via cell viability assay, Apoptosis analysis, and Western blot analysis. The findings showed that a 24 h-treatment of 0.25-4 μM OTA could significantly reduced the cell viability (P < 0.05), which notably increased with the addition of chloroquine and sodium phenylbutyrate, while decreased with the addition of rapamycin and tunicamycin as compared to group OTA (P < 0.05). A 24 h-treatment of 1-4 μM OTA could markedly induce Apoptosis via increasing the protein expressions of GRP78, p-eIF2α, Chop, LC3B-II, Bak, and Bax, and inhibiting the protein expressions of DDRGK1, UBA5, Lonp1, Tex264, FAM134B, p-mTOR, p62, and Bcl-2 in HK-2 cells (P < 0.05). In conclusion, OTA activated ERS, unfolded protein response, and subsequent excessive ER-phagy, thus inducing Apoptosis, and the vicious cycle between excessive ER-phagy and ERS could further promote Apoptosis in vitro.

Keywords

Apoptosis; ER-Phagy; Endoplasmic reticulum stress; Ochratoxin a; UFMylation.

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