title: Characterization of superoxide dismutases in cardiac progenitor cells demonstrates a critical role for manganese superoxide dismutase.
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.
authors: Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30322, USA.
authors: Gokulakrishnan
authors: G
authors: Seshadri
authors: Pao Lin
authors: PL
authors: Che
authors: Archana V
authors: AV
authors: Boopathy
authors: Michael E
authors: ME
authors: Davis
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D004789:Enzyme Activation; D057075:Enzyme Assays; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D018384:Oxidative Stress; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D013997:Time Factors; D014162:Transfection; D019820:Xanthine / Q000009:adverse effects; D014969:Xanthine Oxidase / Q000009:adverse effects; D000099156:Superoxide Dismutase 2
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019820:Xanthine; D014969:Xanthine Oxidase; D000099156:Superoxide Dismutase 2; C000606292:Sod1 protein, rat