Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
J Korean Med Sci. 2013 Mar;28(3):366-73. doi: 10.3346/jkms.2013.28.3.366. Epub 2013 Mar 4.
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.
在这项研究中，我们探索了人精脒脱羧酶 (ADC) 的潜力，以增强间充质干细胞 (MSCs) 在宿主组织不利环境中的存活能力，因为 MSCs 的低存活率是细胞移植治疗中的一个问题。为了解决这个问题，过表达人 ADC 的人 MSCs 用 H2O2 处理，并检查了由此产生的细胞内事件。首先，我们检查了人 ADC 是否在人 MSCs 中过表达。然后，我们研究了与细胞存活或死亡相关的事件。我们发现，人 ADC 的过表达增加了甲臜的产生，减少了 caspase 3 的激活，以及暴露于 H2O2 的人 MSCs 中 FITC、hoechst 或碘化丙啶阳性细胞的数量。为了阐明这些现象的基础，我们检查了 AKT、CREB 和 BDNF。我们发现，人 ADC 的过表达在暴露于 H2O2 的人 MSCs 中磷酸化 AKT 和 CREB，并增加了 BDNF 水平。这些蛋白质的变化可能与胍丁胺的增加有关。总之，我们的数据表明，人 ADC 的过表达刺激了促生存因子，以保护人 MSCs 免受 H2O2 毒性的影响。总之，本研究结果支持 ADC 可以增强 MSCs 在宿主组织不利环境中的存活能力。
