Journal of Cluster Science ( IF 2.7 ) Pub Date : 2021-08-18 , DOI: 10.1007/s10876-021-02152-y Hamed Haghi-Aminjan 1 , Maryam Baeeri 2 , Madiha Khalid 2 , Mahban Rahimifard 2 , Elaheh Mahdizadeh 2 , Mohammad Abdollahi 2, 3 , Mohammad Reza Hooshangi Shayesteh 3
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Abstract
Oxidative stress induces cell senescence and aging. Cell senescence is an irreversible cell cycle arrest mechanism responsible for various pathological diseases and aging. Cerium oxide nanoparticles (CeO2 NPs) have been found to have anti-oxidant effects with a capacity to scavenge free radicals. With this background, we aimed to investigate the senolytic property of CeO2 NPs on mouse embryonic fibroblasts (NIH3T3). NIH3T3 cells were exposed to CeO2 NPs with or without hydrogen peroxide (H2O2). The senolytic effect of CeO2 NPs was evaluated by measuring reactive oxygen species (ROS) production, lipid peroxidation (LPO), β-galactosidase, cell cycle phase analysis, and expression of p21, p38, p53, and NF-кB genes. EC50 of CeO2 NPs significantly reduced the β-galactosidase activity in NIH3T3 cells without apparent cytotoxicity and generation of ROS. Also, it decreased LPO, and expression of IL-6. The number of cells increased significantly, indicating that CeO2 NPs can reverse cell senescence and cell cycle arrest in the S phase. Also, p21, p38, p53, and NF-кB gene expressions were significantly down-regulated. CeO2 NPs as a senolytic or inhibitor of senescence can attenuate the senescence-inducing signal transduction pathways, i.e., p38/ NF-кB and p53/p21. It reduced the production of ROS and LPO and the expression of IL-6.
Graphic Abstract
中文翻译：
通过减弱 p38/NF-кB 和 p53/p21 信号通路对氧化铈纳米颗粒 (CeO2 NPs) 的衰老作用
摘要
氧化应激诱导细胞衰老和老化。细胞衰老是一种不可逆的细胞周期停滞机制，导致各种病理疾病和衰老。已发现氧化铈纳米颗粒 (CeO 2 NPs) 具有抗氧化作用，具有清除自由基的能力。在此背景下，我们旨在研究 CeO 2 NPs 对小鼠胚胎成纤维细胞 (NIH3T3)的衰老特性。NIH3T3 细胞暴露于有或没有过氧化氢 (H 2 O 2 ) 的CeO 2 NPs 。CeO 2的衰老作用通过测量活性氧 (ROS) 产生、脂质过氧化 (LPO)、β-半乳糖苷酶、细胞周期相位分析以及 p21、p38、p53 和 NF-κB 基因的表达来评估 NP。CeO 2 NPs的EC 50显着降低了NIH3T3细胞中的β-半乳糖苷酶活性，而没有明显的细胞毒性和ROS的产生。此外，它还降低了 LPO 和 IL-6 的表达。细胞数量显着增加，表明CeO 2 NPs可以逆转S期的细胞衰老和细胞周期停滞。此外，p21、p38、p53 和 NF-кB 基因表达显着下调。氧化铈2NPs 作为衰老抑制剂或衰老抑制剂可以减弱诱导衰老的信号转导途径，即 p38/NF-кB 和 p53/p21。它减少了 ROS 和 LPO 的产生以及 IL-6 的表达。
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