PMID- 25025394
OWN - NLM
STAT- MEDLINE
DCOM- 20160308
LR  - 20211214
IS  - 1369-1635 (Electronic)
IS  - 0953-7104 (Print)
IS  - 0953-7104 (Linking)
VI  - 26
IP  - 5
DP  - 2015
TI  - Mitoquinone restores platelet production in irradiation-induced thrombocytopenia.
PG  - 459-66
LID - 10.3109/09537104.2014.935315 [doi]
AB  - Myelodysplastic syndromes (MDS) are hallmarked by cytopenia and dysplasia of 
      hematopoietic cells, often accompanied by mitochondrial dysfunction and increases 
      of reactive oxygen species (ROS) within affected cells. However, it is not known 
      whether the increase in ROS production is an instigator or a byproduct of the 
      disease. The present investigation shows that mice lacking immediate early 
      responsive gene X-1 (IEX-1) exhibit lineage specific increases in ROS production 
      and abnormal cytology upon radiation in blood cell types commonly identified in 
      MDS. These affected cell lineages chiefly have the bone marrow as a primary site 
      of differentiation and maturation, while cells with extramedullary 
      differentiation and maturation like B- and T-cells remain unaffected. Increased 
      ROS production is likely to contribute significantly to irradiation-induced 
      thrombocytopenia in the absence of IEX-1 as demonstrated by effective reversal of 
      the disorder after mitoquinone (MitoQ) treatment, a mitochondria-specific 
      antioxidant. MitoQ reduced intracellular ROS production within megakaryocytes and 
      platelets. It also normalized mitochondrial membrane potential and superoxide 
      production in platelets in irradiated, IEX-1 deficient mice. The lineage-specific 
      effects of mitochondrial ROS may help us understand the etiology of 
      thrombocytopenia in association with MDS in a subgroup of the patients.
FAU - Ramsey, Haley
AU  - Ramsey H
AD  - Department of Dermatology, Wellman Center for Photomedicine, Massachusetts 
      General Hospital (MGH), Harvard Medical School (HMS) , Boston , MA and.
FAU - Zhang, Qi
AU  - Zhang Q
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
DEP - 20140715
PL  - England
TA  - Platelets
JT  - Platelets
JID - 9208117
RN  - 0 (Antioxidants)
RN  - 0 (IEX-1 protein, mouse)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (Reactive Oxygen Species)
RN  - 11062-77-4 (Superoxides)
RN  - 1339-63-5 (Ubiquinone)
RN  - 47BYS17IY0 (mitoquinone)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Blood Platelets/metabolism
MH  - Bone Marrow/metabolism
MH  - Cell Lineage/genetics
MH  - Disease Models, Animal
MH  - Immediate-Early Proteins/genetics/metabolism
MH  - Megakaryocytes/drug effects/metabolism/radiation effects
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria/metabolism
MH  - Organophosphorus Compounds/*pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Superoxides/metabolism
MH  - Thrombocytopenia/*blood/drug therapy/*etiology
MH  - Thrombopoiesis/*drug effects/*radiation effects
MH  - Ubiquinone/*analogs & derivatives/pharmacology
MH  - Whole-Body Irradiation
PMC - PMC4382457
MID - NIHMS635534
OTO - NOTNLM
OT  - Megakaryocytes
OT  - Mitoquinone
OT  - Reactive Oxygen Species
OT  - Thrombocytopenia
EDAT- 2014/07/16 06:00
MHDA- 2016/03/10 06:00
PMCR- 2016/01/01
CRDT- 2014/07/16 06:00
PHST- 2014/07/16 06:00 [entrez]
PHST- 2014/07/16 06:00 [pubmed]
PHST- 2016/03/10 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 10.3109/09537104.2014.935315 [doi]
PST - ppublish
SO  - Platelets. 2015;26(5):459-66. doi: 10.3109/09537104.2014.935315. Epub 2014 Jul 
      15.