Radu Mihaela, Dinu Diana, Sima Cornelia, Burlacu Radu, Hermenean Anca, Ardelean Aurel, Dinischiotu Anca
Department of Biochemistry and Molecular Biology, University of Bucharest, 91-95 Splaiul Independentei, Bucharest 050095, Romania; Department of Histology, Faculty of Medicine, Pharmacy and Dentistry, Vasile Goldis Western University of Arad, 1 Feleacului, Arad 310396, Romania.
Department of Biochemistry and Molecular Biology, University of Bucharest, 91-95 Splaiul Independentei, Bucharest 050095, Romania.
Toxicol In Vitro. 2015 Oct;29(7):1492-502. doi: 10.1016/j.tiv.2015.06.002. Epub 2015 Jun 9.
Magnetite nanoparticles (MNP) have attracted great interest for biomedical applications due to their unique chemical and physical properties, but the MNP impact on human health is not fully known. Consequently, our study proposes to highlight the biochemical mechanisms that underline the toxic effects of MNP on a human lung fibroblast cell line (MRC-5). The cytotoxicity generated by MNP in MRC-5 cells was dose and time-dependent. MNP-treated MRC-5 cells accumulated large amount of iron and reactive oxygen species (ROS) and exhibited elevated antioxidant scavenger enzymes. Reduced glutathione (GSH) depletion and enhanced lipid peroxidation (LPO) processes were also observed. The cellular capacity to counteract the oxidative damage was sustained by high levels of heat shock protein 60 (Hsp60), a protein that confers resistance against ROS attack and inhibition of cell death. While significant augmentations in nitric oxide (NO) and prostaglandine E2 (PGE2) levels were detected after 72 h of MNP-exposure only, caspase-1 was activated earlier starting with 24h post-treatment. Taken together, our results suggest that MRC-5 cells have the capacity to develop cell protection mechanisms against MNP. Detailed knowledge of the mechanisms induced by MNP in cell culture could be essential for their prospective use in various in vivo biochemical applications.
由于其独特的化学和物理性质,磁铁矿纳米颗粒(MNP)在生物医学应用中引起了极大的关注,但MNP对人类健康的影响尚未完全明确。因此,我们的研究旨在突出强调MNP对人肺成纤维细胞系(MRC-5)产生毒性作用的生化机制。MNP在MRC-5细胞中产生的细胞毒性具有剂量和时间依赖性。经MNP处理的MRC-5细胞积累了大量的铁和活性氧(ROS),并表现出抗氧化清除酶水平升高。还观察到还原型谷胱甘肽(GSH)耗竭和脂质过氧化(LPO)过程增强。高水平的热休克蛋白60(Hsp60)维持了细胞抵抗氧化损伤的能力,该蛋白可赋予细胞抵抗ROS攻击和抑制细胞死亡的能力。仅在MNP暴露72小时后检测到一氧化氮(NO)和前列腺素E2(PGE2)水平显著升高,而半胱天冬酶-1在处理后24小时开始较早被激活。综上所述,我们的结果表明MRC-5细胞有能力发展针对MNP的细胞保护机制。详细了解MNP在细胞培养中诱导的机制对于其在各种体内生化应用中的前瞻性使用可能至关重要。