PMID- 27513663
OWN - NLM
STAT- MEDLINE
DCOM- 20170803
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 8
DP  - 2016
TI  - Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and 
      TCH346-Insensitive Nuclear Translocation of GAPDH.
PG  - e0160982
LID - 10.1371/journal.pone.0160982 [doi]
LID - e0160982
AB  - 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.
FAU - Snider, Natasha T
AU  - Snider NT
AD  - Department of Cell Biology and Physiology, University of North Carolina, Chapel 
      Hill, NC, 27599, United States of America.
FAU - Portney, Daniel A
AU  - Portney DA
AD  - Department of Molecular & Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, 48109, United States of America.
FAU - Willcockson, Helen H
AU  - Willcockson HH
AD  - Department of Cell Biology and Physiology, University of North Carolina, Chapel 
      Hill, NC, 27599, United States of America.
FAU - Maitra, Dhiman
AU  - Maitra D
AD  - Department of Molecular & Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, 48109, United States of America.
FAU - Martin, Hope C
AU  - Martin HC
AD  - Department of Molecular & Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, 48109, United States of America.
FAU - Greenson, Joel K
AU  - Greenson JK
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, United 
      States of America.
FAU - Omary, M Bishr
AU  - Omary MB
AD  - Department of Molecular & Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, 48109, United States of America.
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, 
      United States of America.
AD  - Veterans Administration Ann Arbor Health Care System, Ann Arbor, MI, 48105, 
      United States of America.
LA  - eng
GR  - R25 DK088752/DK/NIDDK NIH HHS/United States
GR  - P30 DK034987/DK/NIDDK NIH HHS/United States
GR  - P30 DK034933/DK/NIDDK NIH HHS/United States
GR  - K01 DK093776/DK/NIDDK NIH HHS/United States
GR  - R03 DK102450/DK/NIDDK NIH HHS/United States
GR  - R01 DK052951/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20160811
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Oxepins)
RN  - 0 (dibenzo(b,f)oxepin-10-ylmethyl-methyl-prop-2-ynyl-amine)
RN  - 362O9ITL9D (Acetaminophen)
RN  - 3K9958V90M (Ethanol)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
SB  - IM
MH  - Acetaminophen/*toxicity
MH  - Analgesics, Non-Narcotic/toxicity
MH  - Animals
MH  - Cell Nucleus/metabolism
MH  - Central Nervous System Depressants/toxicity
MH  - Chemical and Drug Induced Liver Injury/*drug therapy
MH  - Drug Synergism
MH  - Ethanol/*toxicity
MH  - Female
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/*metabolism
MH  - Liver/*drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxepins/*pharmacology
MH  - Protein Transport/*drug effects
PMC - PMC4981434
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/08/12 06:00
MHDA- 2017/08/05 06:00
PMCR- 2016/08/11
CRDT- 2016/08/12 06:00
PHST- 2016/05/20 00:00 [received]
PHST- 2016/07/26 00:00 [accepted]
PHST- 2016/08/12 06:00 [entrez]
PHST- 2016/08/12 06:00 [pubmed]
PHST- 2017/08/05 06:00 [medline]
PHST- 2016/08/11 00:00 [pmc-release]
AID - PONE-D-16-20095 [pii]
AID - 10.1371/journal.pone.0160982 [doi]
PST - epublish
SO  - PLoS One. 2016 Aug 11;11(8):e0160982. doi: 10.1371/journal.pone.0160982. 
      eCollection 2016.