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Characterization of superoxide dismutases in cardiac progenitor cells demonstrates a critical role for manganese superoxide dismutase.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Seshadri, Gokulakrishnan Che, Pao Lin Boopathy, Archana V. Davis, Michael E.
Description	Country affiliation: United States Author Affiliation: Seshadri G ( Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30322, USA.)
Abstract	Transplantation of cardiac progenitor cells (CPCs) is currently in early clinical testing as a potential therapeutic strategy. Superoxide is increased in the ischemic myocardium and poor survival of cells is one of the major limitations of cell transplantation therapy. Superoxide dismutase (SOD) levels were analyzed in c-kit-positive CPCs isolated from rat myocardium to identify their roles in protection against oxidative stress-induced apoptosis in vitro. CPCs were subjected to oxidative stress using xanthine/xanthine oxidase (XXO) and little apoptosis was detected. CPCs contained significantly higher levels of SOD1 and SOD2 as compared with adult cardiac cell types, both at the protein and activity levels. Both SOD1 and SOD2 were increased by XXO at the mRNA and protein level, suggesting compensatory adaptation. Only knockdown of SOD2 and not SOD1 with siRNA sensitized the cells to XXO-apoptosis, despite only accounting for 10% of total SOD levels. Finally, we found XXO activated Akt within 10 min, and this regulated both SOD2 gene expression and protection against apoptosis. Rat CPCs are resistant to superoxide-induced cell death, primarily through higher levels of SOD2 compared to adult cardiac-derived cells. Exposure to superoxide increases expression of SOD2 in an Akt-dependent manner and regulates CPC survival during oxidative stress.
File Format	HTM / HTML
ISSN	15473287
e-ISSN	15578534
DOI	10.1089/scd.2012.0191
Journal	Stem Cells and Development
Issue Number	17
Volume Number	21
Language	English
Publisher	Mary Ann Liebert, Inc.
Publisher Date	2012-11-20
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cell Biology Discipline Hematology Gene Expression Regulation, Enzymologic Myocardium Cytology Myocytes, Cardiac Enzymology Stem Cells Superoxide Dismutase Metabolism Animals Apoptosis Cell Survival Enzyme Activation Enzyme Assays Fibroblasts Drug Effects Gene Knockdown Techniques Oxidative Stress Phosphorylation Proto-oncogene Proteins C-akt Genetics Proto-oncogene Proteins C-kit Rna, Messenger Rna, Small Interfering Rats, Sprague-dawley Time Factors Transfection Xanthine Adverse Effects Xanthine Oxidase Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Hematology

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Characterization of Superoxide Dismutases in Cardiac Progenitor Cells Demonstrates a Critical Role for Manganese Superoxide Dismutase

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Characterization of superoxide dismutases in cardiac progenitor cells demonstrates a critical role for manganese superoxide dismutase.