Curcumin protects murine lung mesenchymal stem cells from H2O2 by modulating the Akt/Nrf2/HO-1 pathway

Curcumin protects murine lung mesenchymal stem cells from H2O2 by modulating the Akt/Nrf2/HO-1 pathway
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姜黄素通过调节 Akt/Nrf2/HO-1 通路保护小鼠肺间充质干细胞免受 H2O2 的影响

DOI:
10.1177/0300060520910665
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发表时间:
2020-04-01
影响因子:
1.6
通讯作者:
Liu, Liangji
Liu, Liangji
中科院分区:
医学4区
文献类型:
--
作者:
Ke, Shiwen;Zhang, Yuanbing;Liu, Liangji

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目的 特发性肺纤维化微环境中的氧化应激会降低肺间充质干细胞 (LMSC) 的存活率,导致疾病进展。在此,研究了姜黄素 (CUR) 对过氧化氢 (H2O2) 介导的小鼠 LMSC 损伤的影响。方法采用流式细胞仪检测细胞凋亡、活性氧、线粒体膜电位。通过蛋白质印迹分析评估 B 细胞淋巴瘤 2 (Bcl-2)、Bcl-2 相关 x (Bax)、裂解 caspase-3、蛋白激酶 B (PKB/Akt)、磷酸化 Akt、核因子红细胞 2 相关因子 2 (Nrf2) 和血红素加氧酶 -1 (HO-1) 的蛋白水平。结果 2.5、5、10μM CUR组细胞凋亡率分别为23.27%±0.31%、14.87%±0.41%、6.47%±0.50%,均低于H2O2组(24.46%±1.35%)。与 H2O2 组相比,CUR 组的活性氧水平降低,而线粒体膜电位水平以浓度依赖性方式升高。与H2O2组相比,所有CUR组均显示cleaved caspase-3表达减少,Nrf2和HO-1表达增加,Bcl-2/Bax和p-Akt/Akt比值增加。结论 CUR 对 H2O2 介导的小鼠 LMSCs 损伤的保护作用可能是通过 Akt/Nrf2/HO-1 信号通路介导的。
Objectives Oxidative stress within the idiopathic pulmonary fibrosis microenvironment decreases the survival of lung mesenchymal stem cells (LMSCs), resulting in disease progression. Herein, the effects of curcumin (CUR) against hydrogen peroxide (H2O2)-mediated damage to murine LMSCs were examined. Methods Apoptosis, reactive oxygen species, and mitochondrial membrane potential were detected by flow cytometry. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated x (Bax), cleaved caspase-3, protein kinase B (PKB/Akt), phosphorylated-Akt, nuclear factor erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were evaluated by western blot analysis. Results Apoptosis rates in the 2.5, 5, and 10 µM CUR groups were 23.27% ± 0.31%, 14.87% ±0.41%, and 6.47% ± 0.50%, respectively, all of which were lower than in the H2O2 group (24.46% ± 1.35%). Reactive oxygen species levels were decreased, while mitochondrial membrane potential levels were increased in concentration-dependent manners in the CUR groups compared with the H2O2 group. Compared with the H2O2 group, all CUR groups showed reduced cleaved caspase-3 expression, increased Nrf2 and HO-1 expression, and increased Bcl-2/Bax and p-Akt/Akt ratios. Conclusions The protective effects of CUR against H2O2-mediated damage in murine LMSCs may be mediated through the Akt/Nrf2/HO-1 signaling pathway.