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维生素 E 对猪脂肪组织来源间充质干细胞在过氧化氢诱导的氧化应激中的细胞保护作用。

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

机构信息

Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center-Campbell Clinic, Memphis, TN, USA.

Memphis VA Medical Center, Memphis, TN, USA.

出版信息

Cell Tissue Res. 2018 Oct;374(1):111-120. doi: 10.1007/s00441-018-2857-3. Epub 2018 Jun 27.

Abstract

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 (HO)-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 HO-induced oxidative stress. The oxidative stress was induced by treating pASCs with 500 μM HO with or without vitamin E. Viability of pASCs is enhanced after vitamin E treatment. In addition, reduced cellular toxicity, total NO level, PGE 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.

摘要

间充质干细胞 (MSCs) 对抗氧化应激和炎症的存活对于有效的干细胞治疗至关重要。活性氧 (ROS) 导致细胞凋亡并释放炎症介质。脂肪来源的干细胞 (ASCs) 因其抗炎和抗氧化活性而显示出用于干细胞治疗的潜力。先前,我们已经证明了维生素 E 对大鼠骨髓间充质干细胞 (MSCs) 中过氧化氢 (HO) 诱导的氧化应激的益处。在这项研究中,我们旨在评估维生素 E 处理对猪脂肪间充质干细胞 (pASCs) 对抗 HO 诱导的氧化应激的影响。通过用 500 μM HO 处理 pASCs 诱导氧化应激,或用或不用维生素 E 处理 pASCs。维生素 E 处理后,pASCs 的活力增强。此外,在维生素 E 处理后观察到细胞毒性降低、总 NO 水平、PGE 产生和 caspase-3 活性降低。用维生素 E 处理的 pASCs 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,抗凋亡和存活基因的表达上调,即 BCL2、BCL2L1 和 MCL1。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针对氧化应激和炎症特征的疾病的有效干细胞治疗。

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