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NMR-based metabonomic analyses of the effects of ultrasmall superparamagnetic particles of iron oxide (USPIO) on macrophage metabolism

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Abstract

The metabonomic changes in murine RAW264.7 macrophage-like cell line induced by ultrasmall superparamagnetic particles of iron oxides (USPIO) have been investigated, by analyzing both the cells and culture media, using high-resolution NMR in conjunction with multivariate statistical methods. Upon treatment with USPIO, macrophage cells showed a significant decrease in the levels of triglycerides, essential amino acids such as valine, isoleucine, and choline metabolites together with an increase of glycerophospholipids, tyrosine, phenylalanine, lysine, glycine, and glutamate. Such cellular responses to USPIO were also detectable in compositional changes of cell media, showing an obvious depletion of the primary nutrition molecules, such as glucose and amino acids and the production of end-products of glycolysis, such as pyruvate, acetate, and lactate and intermediates of TCA cycle such as succinate and citrate. At 48 h treatment, there was a differential response to incubation with USPIO in both cell metabonome and medium components, indicating that USPIO are phagocytosed and released by macrophages. Furthermore, information on cell membrane modification can be derived from the changes in choline-like metabolites. These results not only suggest that NMR-based metabonomic methods have sufficient sensitivity to identify the metabolic consequences of murine RAW264.7 macrophage-like cell line response to USPIO in vitro, but also provide useful information on the effects of USPIO on cellular metabolism.

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Acknowledgments

We acknowledge the financial supports from the National Natural Science Foundation of China (20605025, 20825520, and 20921004), and the Chinese Academy of Sciences. We also thank Dr. Hang Zhu, Wuhan Institute of Physics and Mathematics, for modifying the matlab scripts used for color-coded loading plots.

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  1. Jing Zhao

    Present address: China Institute of Atomic Energy, Beijing, China

Authors and Affiliations

  1. State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, The Chinese Academy of Sciences, Wuhan, 430071, China

    Jianghua Feng, Fuhua Hao & Huiru Tang

  2. National Laboratory of Biomacromolecules, Institute of Biophysics, The Chinese Academy of Sciences, Beijing, China

    Jing Zhao & Chang Chen

  3. Singapore Bioimaging Consortium Agency for Science, Technology and Research (A*STAR), Singapore, Singapore

    Kishore Bhakoo

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  1. Jianghua Feng
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Correspondence to Huiru Tang.

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Feng, J., Zhao, J., Hao, F. et al. NMR-based metabonomic analyses of the effects of ultrasmall superparamagnetic particles of iron oxide (USPIO) on macrophage metabolism. J Nanopart Res 13, 2049–2062 (2011). https://doi.org/10.1007/s11051-010-9959-5

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