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Overexpression of Human Arginine Decarboxylase Rescues Human Mesenchymal Stem Cells against H2O2 Toxicity through Cell Survival Protein Activation

 Su Kyoung Seo  ;  Wonsuk Yang  ;  Yu Mi Park  ;  Won Taek Lee  ;  Kyung Ah Park  ;  Jong Eun Lee 
 JOURNAL OF KOREAN MEDICAL SCIENCE, Vol.28(3) : 366-373, 2013 
Journal Title
Issue Date
Apoptosis/drug effects* ; Brain-Derived Neurotrophic Factor/metabolism ; Carboxy-Lyases/genetics ; Carboxy-Lyases/metabolism* ; Caspase 3/metabolism ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein/metabolism ; Humans ; Hydrogen Peroxide/toxicity* ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/cytology ; Mesenchymal Stromal Cells/drug effects ; Mesenchymal Stromal Cells/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism
Arginine Decarboxylase ; Cell Survival ; Hydrogen Peroxide ; Mesenchymal Stem Cells ; Retroviral Vector
In this study, we explored the potentiality of human arginine decarboxylase (ADC) to enhance the survival of mesenchymal stem cells (MSCs) against unfavorable milieu of host tissues as the low survival of MSCs is the issue in cell transplantation therapy. To address this, human MSCs overexpressing human ADC were treated with H2O2 and the resultant intracellular events were examined. First, we examined whether human ADC is overexpressed in human MSCs. Then, we investigated cell survival or death related events. We found that the overexpression of human ADC increases formazan production and reduces caspase 3 activation and the numbers of FITC, hoechst, or propidium iodide positive cells in human MSCs exposed to H2O2. To elucidate the factors underlying these phenomena, AKT, CREB, and BDNF were examined. We found that the overexpression of human ADC phosphorylates AKT and CREB and increases BDNF level in human MSCs exposed to H2O2. The changes of these proteins are possibly relevant to the elevation of agmatine. Collectively, our data demonstrate that the overexpression of human ADC stimulates pro-survival factors to protect human MSCs against H2O2 toxicity. In conclusion, the present findings support that ADC can enhance the survival of MSCs against hostile environment of host tissues.
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1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Park, Kyung Ah(박경아)
Lee, Won Taek(이원택) ORCID logo https://orcid.org/0000-0001-7348-9562
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
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