Drug-induced oxidative stress actively prevents caspase activation and hepatocyte apoptosis.

ABSTRACT: Cell death is a fundamental process in health and disease. Emerging research shows the existence of numerous distinct cell death modalities with similar and intertwined signaling pathways, but resulting in different cellular outcomes, raising the need to understand the decision-making steps during cell death signaling. Paracetamol (Acetaminophen, APAP)-induced hepatocyte death includes several apoptotic processes but eventually is executed by oncotic necrosis without any caspase activation. Here, we studied this paradoxical form of cell death and revealed that APAP not only fails to activate caspases but also strongly impedes their activation upon classical apoptosis induction, thereby shifting apoptosis to necrosis. While APAP intoxication results in massive drop in mitochondrial respirat

SUBMITTER: Lambrecht R 

PROVIDER: S-EPMC11381522 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature