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Molecular mechanism of copper–zinc superoxide dismutase activity change exposed to N-acetyl-l-cysteine-capped CdTe quantum dots-induced oxidative damage in mouse primary hepatocytes and nephrocytes

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Abstract

Quantum dots (QDs) are engineered semiconductor nanocrystals with promising application in biomedicine, which have potential toxic effect on biomacromolecules by direct interaction and indirect impact in the body. In this work, the effect of N-acetyl-l-cysteine-capped CdTe quantum dots with fluorescence emission peak at 612 nm (QDs-612) on copper–zinc superoxide dismutase (Cu/ZnSOD) at molecular and cellular level was investigated using isothermal titration calorimetry, spectroscopic techniques, cell counting kit-8, and total SOD assay. The hydrophobic interaction between Cu/ZnSOD and QDs-612 caused static fluorescence quenching of the protein, which was spontaneous with binding constant calculated to be 3.28 × 105 L mol−1. The microenvironment of tyrosine residues, skeleton, and secondary structure of Cu/ZnSOD were changed with adding QDs-612. The molecular Cu/ZnSOD activity was inhibited at different concentrations of QDs-612 as well as the intracellular Cu/ZnSOD activity after 2-h exposure. Compared with the cell viability of hepatocytes and nephrocytes (decreased markedly of the initial level) with higher concentrations of QDs-612 in the absence of vitamin C, the cell viability of these two primary cells increased in the presence of vitamin C, indicating the oxidative damage induced by QDs-612. Therefore, the inhibition of Cu/ZnSOD activity in these two primary cells may be caused by the oxidative damage of massive ROS or direct interaction with QDs-612. This work establishes a new approach to investigate the biological toxicity of CdTe QDs to biomacromolecule from both molecular and cellular perspectives and obtains experimental evidence to thoroughly study the toxicity of CdTe QDs in vivo.

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Abbreviations

QDs:

Quantum dots

SOD:

Superoxide dismutase

ROS:

Reactivated oxygen species

Cu/ZnSOD:

Copper–zinc superoxide dismutase

MnSOD:

Manganese superoxide dismutase

ECSOD:

Extracellular superoxide dismutase

ITC:

Isothermal titration calorimetry

CCK-8:

Cell counting kit-8

QDs-612:

N-acetyl-l-cysteine-capped CdTe quantum dots with fluorescence emission peak at 612 nm

NAC:

N-acetyl-l-cysteine

CAT:

Catalase

Tyr:

Tyrosine

Trp:

Tryptophan

PB:

Phosphate buffer

CD:

Circular dichroism

WST-1:

2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, disodium salt

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Acknowledgments

This work is supported by NSFC (20875055, 21277081, 21477067), the Cultivation Fund of the Key Scientific and Technical Innovation Project, Research Fund for the Doctoral Program of Higher Education and Ministry of Education of China (708058, 20130131110016). Independent innovation program of Jinan (201202083), Science and Technology Development Plan of Shandong Province (2014GSF117027) and Independent innovation foundation of Shandong University natural science projects (2012DX002) are also acknowledged.

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Authors and Affiliations

  1. School of Environmental Science and Engineering, Shandong University, Jinan, 250100, People’s Republic of China

    Haoyu Sun, Erqian Cui & Rutao Liu

  2. School of Environmental Science and Engineering, China–America CRC for Environment & Health, Shandong University, 27# Shanda South Road, Jinan, Shandong Province, 250100, People’s Republic of China

    Haoyu Sun, Erqian Cui & Rutao Liu

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  1. Haoyu Sun
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  3. Rutao Liu
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Correspondence to Rutao Liu.

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Responsible editor: Thomas Braunbeck

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ESM. 1

Fig. S1The structure-based alignment of porcine Cu/ZnSOD and mouse Cu/ZnSOD. Fig. S2: The structure and functional regions of mouse Cu/ZnSOD. Fig. S3: Time-resolved fluorescence decay curves of Cu/ZnSOD in the absence and presence of QDs-612. Fig. S4: CAT activity of primary hepatocytes (a and c) and primary nephrocytes (b and d) after 2 h exposure with different concentrations of QDs-612. (DOCX 293 kb)

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Sun, H., Cui, E. & Liu, R. Molecular mechanism of copper–zinc superoxide dismutase activity change exposed to N-acetyl-l-cysteine-capped CdTe quantum dots-induced oxidative damage in mouse primary hepatocytes and nephrocytes. Environ Sci Pollut Res 22, 18267–18277 (2015). https://doi.org/10.1007/s11356-015-5035-0

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