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.
CITATION STYLE
Snider, N. T., Portney, D. A., Willcockson, H. H., Maitra, D., Martin, H. C., Greenson, J. K., & Omary, M. B. (2016). Ethanol and acetaminophen synergistically induce hepatic aggregation and TCH346-insensitive nuclear translocation of GAPDH. PLoS ONE, 11(8). https://doi.org/10.1371/journal.pone.0160982
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