Ethanol and acetaminophen synergistically induce hepatic aggregation and TCH346-insensitive nuclear translocation of GAPDH

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere0160982
JournalPloS one
Volume11
Issue number8
DOIs
StatePublished - Aug 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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