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

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...

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Autores principales: Snider, Natasha T., Portney, Daniel A., Willcockson, Helen H., Maitra, Dhiman, Martin, Hope C., Greenson, Joel K., Omary, M. Bishr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981434/
https://www.ncbi.nlm.nih.gov/pubmed/27513663
http://dx.doi.org/10.1371/journal.pone.0160982
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author Snider, Natasha T.
Portney, Daniel A.
Willcockson, Helen H.
Maitra, Dhiman
Martin, Hope C.
Greenson, Joel K.
Omary, M. Bishr
author_facet Snider, Natasha T.
Portney, Daniel A.
Willcockson, Helen H.
Maitra, Dhiman
Martin, Hope C.
Greenson, Joel K.
Omary, M. Bishr
author_sort Snider, Natasha T.
collection PubMed
description 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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spelling pubmed-49814342016-08-29 Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH Snider, Natasha T. Portney, Daniel A. Willcockson, Helen H. Maitra, Dhiman Martin, Hope C. Greenson, Joel K. Omary, M. Bishr PLoS One Research Article 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. Public Library of Science 2016-08-11 /pmc/articles/PMC4981434/ /pubmed/27513663 http://dx.doi.org/10.1371/journal.pone.0160982 Text en © 2016 Snider et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Snider, Natasha T.
Portney, Daniel A.
Willcockson, Helen H.
Maitra, Dhiman
Martin, Hope C.
Greenson, Joel K.
Omary, M. Bishr
Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH
title Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH
title_full Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH
title_fullStr Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH
title_full_unstemmed Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH
title_short Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH
title_sort ethanol and acetaminophen synergistically induce hepatic aggregation and tch346-insensitive nuclear translocation of gapdh
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981434/
https://www.ncbi.nlm.nih.gov/pubmed/27513663
http://dx.doi.org/10.1371/journal.pone.0160982
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