Cytoprotective role of vitamin E in porcine adipose-tissue-derived mesenchymal stem cells against hydrogen-peroxide-induced oxidative stress.

Cytoprotective role of vitamin E in porcine adipose-tissue-derived mesenchymal stem cells against hydrogen-peroxide-induced oxidative stress.
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DOI:
10.1007/s00441-018-2857-3
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发表时间:
2018-10
影响因子:
3.6
通讯作者:
Cho H
Cho H
中科院分区:
生物学3区
文献类型:
--
作者:
Bhatti FUR;Kim SJ;Yi AK;Hasty KA;Cho H

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间充质干细胞(MSC)在氧化应激和炎症中的存活对于有效的干细胞治疗至关重要。活性氧(ROS)导致细胞凋亡和炎症介质的释放。脂肪干细胞(ASC)由于其抗炎和抗氧化活性而在干细胞治疗中显示出前景。此前,我们展示了维生素 E 对大鼠骨髓间充质干细胞中过氧化氢 (H2O2) 诱导的氧化应激的益处。在本研究中,我们旨在评估维生素 E 治疗对猪脂肪间充质干细胞 (pASC) 对抗 H2O2 诱导的氧化应激的影响。通过用 500 μM H2O2(含或不含维生素 E)处理 pASC 来诱导氧化应激。维生素 E 处理后,pASC 的活力得到增强。此外,维生素 E 治疗后观察到细胞毒性、总 NO 水平、PGE2 产生和 caspase-3 活性降低。维生素 E 处理的 pASC 的基因表达分析显示,与氧化应激和细胞凋亡相关的基因(即 NOS2、Casp3、p53、BAX、MDM2、NF𝜅B、HIF1α 和 VEGF-A 基因)的表达下调。另一方面,抗凋亡和存活基因(即 BCL2、BCL2L1 和 MCL1)的表达上调。此外,维生素 E 处理后 Akt 的磷酸化减弱。这项研究的结果可能有助于开发有效的干细胞疗法来治疗以氧化应激和炎症为特征的疾病。
Survival of mesenchymal stem cells (MSCs) against oxidative stress and inflammation is vital for effective stem cell therapy. The reactive oxygen species (ROS) result in apoptosis and release of inflammatory mediators. Adipose-derived stem cells (ASCs) have shown promise for stem cell therapy owing to their anti-inflammatory and anti-oxidant activity. Previously, we showed the benefits of vitamin E against hydrogen peroxide (H2O2)-induced oxidative stress in rat bone marrow-derived MSCs. In this study, we aim to evaluate the effect of vitamin E treatment on porcine adipose-derived mesenchymal stem cells (pASCs) against H2O2-induced oxidative stress. The oxidative stress was induced by treating pASCs with 500 μM H2O2 with or without vitamin E. Viability of pASCs is enhanced after vitamin E treatment. In addition, reduced cellular toxicity, total NO level, PGE2 production and caspase-3 activity were observed after vitamin E treatment. Gene expression analysis of vitamin E-treated pASCs showed down-regulated expression for the genes associated with oxidative stress and apoptosis, viz., NOS2, Casp3, p53, BAX, MDM2, NF𝜅B, HIF1α and VEGF-A genes. On the other hand, expression of anti-apoptotic and survival genes was up-regulated, viz., BCL2, BCL2L1 and MCL1. Furthermore, phosphorylation of Akt was attenuated following vitamin E treatment. The findings of this study may help in developing effective stem cell therapy for the diseases characterized by the oxidative stress and inflammation.
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