CHOP aggravates hepatocyte apoptosis upon endoplasmic reticulum stress by downregulating autophagy

Résumé fourni par la source

Endoplasmic reticulum (ER) stress-induced apoptosis plays a crucial role in various liver diseases. Hepatocytes respond to ER stress by activating the unfolded protein response and autophagy, which is essential for maintaining ER homeostasis. However, failure to restore ER balance via autophagy contributes to apoptosis. In this study, we aimed to explore the role of C/EBP homologous protein (CHOP) in regulating ER stress-induced apoptosis in rat hepatocytes. We found that CHOP downregulates autophagy, aggravating apoptosis. Our results revealed that inhibition of CHOP expression enhanced autophagy and reduced DTT-induced apoptosis in BRL-3A cells, whereas CHOP overexpression worsened apoptosis. Chromatin immunoprecipitation assays revealed that CHOP negatively regulates autophagy-related genes, such as ATG12, ATG5, and LC3. These findings suggest that CHOP modulation plays a crucial role in ER stress-induced hepatocyte apoptosis by regulating autophagy. • Endoplasmic reticulum (ER) stress triggers apoptosis in liver diseases via C/EBP homologous protein (CHOP) and autophagy. • Autophagy is crucial for maintaining ER homeostasis in hepatocytes. • CHOP overexpression leads to reduced autophagy and increased apoptosis. • Pretreatment with rapamycin mitigates ER stress-related cell death. • Silencing CHOP enhances autophagy and decreases apoptosis in stressed cells.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.