Si/SiO2 quantum dots cause cytotoxicity in lung cells through redox homeostasis imbalance

Miruna S Stan; Indira Memet; Cornelia Sima; Traian Popescu; Valentin S Teodorescu; Anca Hermenean; Anca Dinischiotu

doi:10.1016/j.cbi.2014.06.020

Si/SiO2 quantum dots cause cytotoxicity in lung cells through redox homeostasis imbalance

Chem Biol Interact. 2014 Sep 5:220:102-15. doi: 10.1016/j.cbi.2014.06.020. Epub 2014 Jun 30.

Authors

Miruna S Stan¹, Indira Memet¹, Cornelia Sima², Traian Popescu³, Valentin S Teodorescu³, Anca Hermenean⁴, Anca Dinischiotu⁵

Affiliations

¹ Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania.
² National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, 077125 Bucharest-Magurele, Romania.
³ National Institute of Materials Physics, 105 bis Atomistilor, 077125 Bucharest-Magurele, Romania.
⁴ Department of Histology, Faculty of Medicine, Pharmacy and Dentistry, Vasile Goldis Western University of Arad, 86 Rebreanu, 310414 Arad, Romania; Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Rebreanu, 310414 Arad, Romania.
⁵ Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania. Electronic address: ancadinischiotu@yahoo.com.

PMID: 24992398
DOI: 10.1016/j.cbi.2014.06.020

Abstract

Si/SiO2 quantum dots (QDs) are novel particles with unique physicochemical properties that promote them as potential candidates for biomedical applications. Although their interaction with human cells has been poorly investigated, oxidative stress appears to be the main factor involved in the cytotoxicity of these nanoparticles. In this study, we show for the first time the influence of Si/SiO2 QDs on cellular redox homeostasis and glutathione distribution in human lung fibroblasts. The nanoparticles morphology, composition and structure have been investigated using high resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD) analysis. MRC-5 cells (human lung fibroblasts) were incubated with various concentrations of Si/SiO2 QDs ranging between 25 and 200 μg/mL for up to 72 h. The results of the MTT and sulforhodamine B assays showed that exposure to QDs led to a time-dependent decrease in cell viability and biomass. The increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels together with the lower glutathione content suggested that the cellular redox homeostasis was altered. Regarding GSH distribution, the first two days of treatment resulted in a localization of GSH mainly in the cytoplasm, while at longer incubation time the nuclear/cytoplasmic ratio indicated a nuclear localization. These modifications of cell redox state also affected the redox status of proteins, which was demonstrated by the accumulation of oxidized proteins and actin S-glutathionylation. In addition, the externalization of phosphatidylserine provided evidence that apoptosis might be responsible for cell death, but necrosis was also revealed. Our results suggest that Si/SiO2 quantum dots exerted cytotoxicity on MRC-5 cells by disturbing cellular homeostasis which had an effect upon protein redox status.

Keywords: Oxidative stress; Protein oxidation; Quantum dots; Reduced glutathione; S-glutathionylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects
Cell Survival / drug effects
Fibroblasts / drug effects
Homeostasis / drug effects*
Humans
Lung / drug effects*
Microscopy, Electron, Transmission
Oxidation-Reduction
Oxidative Stress / drug effects
Quantum Dots / chemistry*
Reactive Oxygen Species
Silicon / toxicity*
Silicon Dioxide / toxicity*
Time Factors

Substances

Reactive Oxygen Species
Silicon Dioxide
Silicon