Document Detail


Ischemia/Reperfusion injury protection by mesenchymal stem cell derived antioxidant capacity.
MedLine Citation:
PMID:  23614555     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mesenchymal stem cell (MSC) transplantation after ischemia/reperfusion (I/R) injury reduces infarct size and improves cardiac function. We used mouse ventricular myocytes (VMs) in an in vitro model of I/R to determine the mechanism by which MSCs prevent reperfusion injury by paracrine signaling. Exposure of mouse VMs to an ischemic challenge depolarized their mitochondrial membrane potential (Ψmito), increased their diastolic Ca(2+), and significantly attenuated cell shortening. Reperfusion of VMs with Ctrl tyrode or MSC-conditioned tyrode (ConT) resulted in a transient increase of the Ca(2+) transient amplitudes in all cells. ConT-reperfused cells exhibited a decreased number early after depolarization (EADs) (ConT: 6.3% vs. Ctrl: 28.4%) and prolonged survival (ConT: 58% vs. Ctrl: 33%). Ψmito rapidly recovered in Ctrl as well as ConT-treated VMs on reperfusion; however, in Ctrl solution, an exaggerated hyperpolarization of Ψmito was determined that preceded the collapse of Ψmito. The ability of ConT to attenuate the hyperpolarization of Ψmito was suppressed on inhibition of the PI3K/Akt signaling pathway or IK,ATP. However, protection of Ψmito was best mimicked by the reactive oxygen species (ROS) scavenger mitoTEMPO. Analysis of ConT revealed a significant antioxidant capacity that was linked to the presence of extracellular superoxide dismutase (SOD3) in ConT. In conclusion, MSC ConT protects VMs from simulated I/R injury by its SOD3-mediated antioxidant capacity and by delaying the recovery of Ψmito through Akt-mediated opening of IK,ATP. These changes attenuate reperfusion-induced ROS production and prevent the opening of the permeability transition pore and arrhythmic Ca(2+) release.
Authors:
Jaime DeSantiago; Dan J Bare; Kathrin Banach
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-06-11
Journal Detail:
Title:  Stem cells and development     Volume:  22     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-08-30     Completed Date:  2014-04-07     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2497-507     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / metabolism*
Bone Marrow Cells / metabolism
Calcium / metabolism
Cell Size
Cell Survival
Cells, Cultured
Isotonic Solutions / pharmacology
Membrane Potential, Mitochondrial / drug effects
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stromal Cells / metabolism*
Mice
Mice, Inbred C57BL
Myocardial Reperfusion Injury / metabolism*,  prevention & control,  therapy*
Myocardium / metabolism
Myocytes, Cardiac / metabolism
Organophosphorus Compounds / metabolism
Oxidation-Reduction
Oxidative Stress / drug effects
Piperidines / metabolism
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects
Superoxide Dismutase / metabolism*
Grant Support
ID/Acronym/Agency:
HL089617/HL/NHLBI NIH HHS; HL089617-03S1/HL/NHLBI NIH HHS; R01 HL089617/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Isotonic Solutions; 0/MitoTEMPO; 0/Organophosphorus Compounds; 0/Piperidines; 0/Reactive Oxygen Species; 0/Tyrode's solution; EC 1.15.1.1/Sod3 protein, mouse; EC 1.15.1.1/Superoxide Dismutase; SY7Q814VUP/Calcium
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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