Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells
Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells
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DOI：
10.1016/j.tox.2011.02.010
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发表时间：
2011-05-10
期刊：
影响因子：
4.5
通讯作者：
Alrokayan, Salman A.
中科院分区：
文献类型：
--
作者：
Ahamed, Maqusood;Akhtar, Mohd Javed;Alrokayan, Salman A.
由于具有良好的化学稳定性和热稳定性的有趣的磁和电性质，镍铁氧体纳米颗粒被用于许多应用，包括磁共振成像，药物递送和热疗。最近的研究表明，铁酸镍纳米颗粒在哺乳动物细胞中产生细胞毒性。然而，在细胞和分子水平上，关于镍铁氧体纳米颗粒的毒性的信息非常有限。本研究的目的是调查的细胞毒性，氧化应激和诱导凋亡的良好表征的镍铁氧体纳米粒子（尺寸26 nm）在人肺上皮细胞（A549）。MTT法、NRU法和LDH法检测结果显示，纳米铁酸镍对A549细胞具有剂量依赖性的细胞毒作用。铁酸镍纳米颗粒也被发现诱导氧化应激，这通过产生活性氧（ROS）和耗尽抗氧化剂谷胱甘肽（GSH）来证明。此外，与抗氧化剂L-抗坏血酸的共处理减轻了由于铁酸镍纳米颗粒引起的ROS产生和GSH耗尽，这表明了氧化应激的潜在机制。实时荧光定量PCR检测结果显示，铁镍纳米颗粒作用于A549细胞后，细胞周期检查点蛋白p53和凋亡蛋白bax、caspase-3和caspase-9的mRNA表达水平显著上调，而抗凋亡蛋白survivin和bcl-2的mRNA表达水平下调。此外，caspase-3和caspase-9酶的活性也显着高于镍铁氧体纳米颗粒暴露的细胞。据我们所知，这是第一个报告显示，镍铁氧体纳米粒子诱导A549细胞凋亡，通过ROS的产生和氧化应激，通过p53，生存素，bax/bcl-2和caspase途径。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Due to the interesting magnetic and electrical properties with good chemical and thermal stabilities, nickel ferrite nanoparticles are being utilized in many applications including magnetic resonance imaging, drug delivery and hyperthermia. Recent studies have shown that nickel ferrite nanoparticles produce cytotoxicity in mammalian cells. However, there is very limited information concerning the toxicity of nickel ferrite nanoparticles at the cellular and molecular level. The aim of this study was to investigate the cytotoxicity, oxidative stress and apoptosis induction by well-characterized nickel ferrite nanoparticles (size 26 nm) in human lung epithelial (A549) cells. Nickel ferrite nanoparticles induced dose-dependent cytotoxicity in A549 cells demonstrated by MTT, NRU and LDH assays. Nickel ferrite nanoparticles were also found to induce oxidative stress evidenced by generation of reactive oxygen species (ROS) and depletion of antioxidant glutathione (GSH). Further, co-treatment with the antioxidant L-ascorbic acid mitigated the ROS generation and GSH depletion due to nickel ferrite nanoparticles suggesting the potential mechanism of oxidative stress. Quantitative real-time PCR analysis demonstrated that following the exposure of A549 cells to nickel ferrite nanoparticles, the level of mRNA expressions of cell cycle checkpoint protein p53 and apoptotic proteins (bax, caspase-3 and caspase-9) were significantly up-regulated, whereas the expression of anti-apoptotic proteins (survivin and bcl-2) were down-regulated. Moreover, activities of caspase-3 and caspase-9 enzymes were also significantly higher in nickel ferrite nanoparticles exposed cells. To the best of our knowledge this is the first report showing that nickel ferrite nanoparticles induced apoptosis in A549 cells through ROS generation and oxidative stress via p53, survivin, bax/bcl-2 and caspase pathways. (C) 2011 Elsevier Ireland Ltd. All rights reserved.