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

Area of Science:

• Toxicology
• Cell Biology
• Molecular Mechanisms

Background:

• Ochratoxin A (OTA) is a prevalent mycotoxin posing significant health risks.
• Previous studies indicated OTA induces cell cycle arrest, apoptosis, and autophagy in gastric cells (GES-1).
• The precise molecular mechanisms behind OTA's cytotoxicity remain incompletely understood.

Purpose of the Study:

• To elucidate the molecular pathways involved in Ochratoxin A-induced toxicity in human gastric epithelial cells (GES-1).
• To investigate the roles of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in OTA's cytotoxic effects.

Main Methods:

• Exposure of GES-1 cells to Ochratoxin A (OTA).
• Assessment of ER stress markers (GRP78, PERK, ATF6, eIF2α, CHOP) and ROS generation.
• Treatment with ER stress inhibitor (4-phenylbutyric acid, 4-PBA) and ROS inhibitor (N-acetylcysteine, NAC).
• Analysis of cell viability, apoptosis, cell cycle (G2 phase), and autophagy markers (LC3B, Beclin-1).

Main Results:

• OTA exposure significantly increased ER stress indicators and ROS production in GES-1 cells.
• 4-PBA treatment reversed OTA-induced apoptosis, cell viability loss, G2 phase arrest, and autophagy.
• NAC administration attenuated OTA-induced ER stress, apoptosis, cell cycle arrest, and autophagy.
• OTA upregulated G2 phase proteins (Cdc2, Cdc25C, cyclinB1) and downregulated autophagy markers (LC3B, Beclin-1).

Conclusions:

• The study identifies a critical role for ROS-mediated ER stress in Ochratoxin A-induced cytotoxicity in gastric cells.
• These findings provide novel insights into the molecular mechanisms of OTA toxicity, highlighting potential therapeutic targets.