Hepatoxicity SIG (Jun 24): The interplay of ER stress and autophagy in APAP toxicity-The Interplay of ER Stress and Autophagy in APAP Toxicity

Video Transcription

Video Summary

Dr. Francisco Javier Cubero delivered an in-depth presentation on hepatotoxicity at the AASLD Hepatotoxicity Special Interest Group. Dr. Cubero, a professor at Universidad Complutense de Madrid, explored the intricate relationship between endoplasmic reticulum (ER) stress, autophagy, and acetaminophen (APAP) toxicity, presenting both published and unpublished data. His research focuses on pathways linking ER stress and autophagy through XBP1, particularly in drug-induced liver injury (DILI). He outlined how XBP1 deletion in hepatocytes mitigates APAP-induced liver damage amid increased autophagy and reduced CYP2E1 activity. Additionally, the role of XBP1 in hepatic stellate cells influencing metabolic diseases like NASH and liver fibrosis was highlighted. The presentation also delved into the involvement of the JNK signaling pathway in APAP toxicity, alongside emerging insights linking NRF2 signaling to liver injury through experiments involving KIPP1 deletion. The talk concluded with discussions on the complexities of these pathways and their implications for liver disease mechanisms and potential therapeutic targets, underscoring the vital role of oxidative and ER stress responses in liver injury contexts.

Keywords

hepatotoxicity

endoplasmic reticulum stress

autophagy

acetaminophen toxicity

XBP1

drug-induced liver injury

JNK signaling pathway

NRF2 signaling

liver fibrosis