title: Overexpression of human arginine decarboxylase rescues human mesenchymal stem cells against H₂O₂ toxicity through cell survival protein activation.
abstract: 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.
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Su Kyoung
authors.initials: SK
authors.lastname: Seo
authors.forename: Wonsuk
authors.initials: W
authors.lastname: Yang
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Park
authors.forename: Won Taek
authors.initials: WT
authors.lastname: Lee
authors.forename: Kyung Ah
authors.initials: KA
authors.lastname: Park
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D002262:Carboxy-Lyases; C019722:arginine decarboxylase
keywords: Arginine Decarboxylase; Cell Survival; Hydrogen Peroxide; Mesenchymal Stem Cells; Retroviral Vector