Article Publish Status: FREE
Abstract Title:

Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH.

Abstract Source:

PLoS One. 2016 ;11(8):e0160982. Epub 2016 Aug 11. PMID: 27513663

Abstract Author(s):

Natasha T Snider, Daniel A Portney, Helen H Willcockson, Dhiman Maitra, Hope C Martin, Joel K Greenson, M Bishr Omary

Article Affiliation:

Natasha T Snider


The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) signals during cellular stress via several post-translational modifications that change its folding properties, protein-protein interactions and sub-cellular localization. We examined GAPDH properties in acute mouse liver injury due to ethanol and/or acetaminophen (APAP) treatment. Synergistic robust and time-dependent nuclear accumulation and aggregation of GAPDH were observed only in combined, but not individual, ethanol/APAP treatments. The small molecule GAPDH-targeting compound TCH346 partially attenuated liver damage possibly via mitochondrial mechanisms, and independent of nuclear accumulation and aggregation of GAPDH. These findings provide a novel potential mechanism for hepatotoxicity caused by combined alcohol and acetaminophen exposure.

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