Open AccessEthanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH
Author(s) -
Natasha T. Snider,
Daniel A. Portney,
Helen H. Willcockson,
Dhiman Maitra,
Hope C. Martin,
Joel K. Greenson,
M. Bishr Omary
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0160982
Subject(s) - glyceraldehyde 3 phosphate dehydrogenase , acetaminophen , chemistry , alcohol dehydrogenase , biochemistry , glyceraldehyde , ethanol , glycolysis , mitochondrion , enzyme , proteome , microbiology and biotechnology , dehydrogenase , biology
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.