PMID- 25466275
OWN - NLM
STAT- MEDLINE
DCOM- 20150728
LR  - 20211214
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Print)
IS  - 1567-5769 (Linking)
VI  - 23
IP  - 2
DP  - 2014 Dec
TI  - Mitochondrial anti-oxidant protects IEX-1 deficient mice from organ damage during 
      endotoxemia.
PG  - 658-63
AB  - Sepsis, a leading cause of mortality in intensive care units worldwide, is often 
      a result of overactive and systemic inflammation following serious infections. We 
      found that mice lacking immediate early responsive gene X-1 (IEX-1) were prone to 
      lipopolysaccharide (LPS) -induced endotoxemia. A nonlethal dose of LPS provoked 
      numerous aberrations in IEX-1 knockout (KO) mice including pancytopenia, 
      increased serum aspartate aminotransferase (AST), and lung neutrophilia, 
      concurrent with liver and kidney damage, followed by death. Given these results, 
      in conjunction with a proven role for IEX-1 in the regulation of reactive oxygen 
      species (ROS) homeostasis during stress, we pre-treated IEX-1 KO mice with 
      Mitoquinone (MitoQ), a mitochondrion-based antioxidant prior to LPS injection. 
      The treatment significantly reduced ROS formation in circulatory cells and 
      protected against pancytopenia and multiple organ failure, drastically increasing 
      the survival rate of IEX-1 KO mice challenged by this low dose of LPS. This study 
      confirms significant contribution of mitochondrial ROS to the etiology of sepsis.
FAU - Ramsey, Haley
AU  - Ramsey H
FAU - Wu, Mei X
AU  - Wu MX
LA  - eng
GR  - R21 CA158756/CA/NCI NIH HHS/United States
GR  - AI089779/AI/NIAID NIH HHS/United States
GR  - RC1 DA028378/DA/NIDA NIH HHS/United States
GR  - R01 AI089779/AI/NIAID NIH HHS/United States
GR  - CA158756/CA/NCI NIH HHS/United States
GR  - DA028378/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Antioxidants)
RN  - 0 (Endotoxins)
RN  - 0 (IEX-1 protein, mouse)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (Reactive Oxygen Species)
RN  - 1339-63-5 (Ubiquinone)
RN  - 47BYS17IY0 (mitoquinone)
RN  - 67924-63-4 (endotoxin, Escherichia coli)
SB  - IM
MH  - Animals
MH  - Antioxidants/administration & dosage/*therapeutic use
MH  - Blood Cell Count
MH  - Data Interpretation, Statistical
MH  - Endotoxemia/blood/chemically induced/genetics/*prevention & control
MH  - Endotoxins/*toxicity
MH  - Immediate-Early Proteins/*deficiency/genetics
MH  - Kaplan-Meier Estimate
MH  - Kidney/drug effects/pathology
MH  - Liver/drug effects/pathology
MH  - Lung/drug effects/pathology
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mice, Knockout
MH  - Mitochondria/*drug effects/metabolism
MH  - Organophosphorus Compounds/administration & dosage/*therapeutic use
MH  - Reactive Oxygen Species/metabolism
MH  - Ubiquinone/administration & dosage/*analogs & derivatives/therapeutic use
PMC - PMC4394602
MID - NIHMS640424
COIS- Declaration of Interest Statement The authors report no declarations of interest. 
      This work is supported by the National Institutes of Health Grants CA158756, 
      AI089779, and DA028378 to M.X.W. H.R. designed and performed the research, 
      analyzed data, and wrote the manuscript. M.X.W. has designed and supervised 
      research and wrote the manuscript. The authors declare no conflict of interest.
EDAT- 2014/12/04 06:00
MHDA- 2015/07/29 06:00
PMCR- 2015/12/01
CRDT- 2014/12/04 06:00
PHST- 2014/07/17 00:00 [received]
PHST- 2014/10/11 00:00 [revised]
PHST- 2014/10/20 00:00 [accepted]
PHST- 2014/12/04 06:00 [entrez]
PHST- 2014/12/04 06:00 [pubmed]
PHST- 2015/07/29 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - S1567-5769(14)00401-9 [pii]
AID - 10.1016/j.intimp.2014.10.019 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2014 Dec;23(2):658-63. doi: 10.1016/j.intimp.2014.10.019.