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In vitro study on the alterations of brain tubulin structure and assembly affected by magnetite nanoparticles

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Abstract

In recent decades, considerable efforts have been made to understand the mechanism of memory, cognition, and relevant neurodegenerative diseases in the human brain. Several studies have shown the importance of microtubule proteins in the memory mechanism and memory dysfunction. Microtubules possess dynamicity, which is essential for functions of neuronal networks. Microtubule-associated proteins, i.e., tau, play vital roles in microtubule stability. On the other hand, the ferromagnetic mineral magnetite (Fe3O4) has been detected in the normal human brain, and elevated levels of magnetite are also observed in the brains of Alzheimer’s disease patients. Therefore, we propose that a relationship between microtubule organization in axons and brain magnetite nanoparticles is possible. In this study we found alterations of microtubule polymerization in the presence of increasing concentrations of magnetite through transmission electron microscopy images and a turbidimetry method. Structural changes of microtubule and tau protein, as an essential microtubule-associated protein for tubulin assembly, were detected via circular dichroism spectroscopy, intrinsic fluorescence, and 8-anilino-1-naphthalenesulfonic acid fluorometry. We predicted three possible binding sites on tau protein and one possible binding site on tubulin dimer for magnetite nanoparticles. Magnetite also causes the morphology of PC12 cells to change abnormally and cell viability to decrease. Finally, we suggest that magnetite changes microtubule dynamics and polymerization through two paths: (1) changing the secondary and tertiary structure of tubulin and (2) binding to either tubulin dimer or tau protein and preventing tau–tubulin interaction.

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Acknowledgments

This research was supported by the Neuroorganic Laboratory at the Institute of Biochemistry and Biophysics, University of Tehran. We are grateful to Maryam Aghamiari, Darian Fard, and Soheil Afsharpour for their help in purifying microtubules and preparing the manuscript.

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Authors and Affiliations

  1. Neuroorganic Laboratory, Institute of Biochemistry and Biophysics (IBB), University of Tehran, PO Box 13145-1384, Tehran, Iran

    Ali Dadras, Gholam Hossein Riazi, Ali Afrasiabi, Ali Naghshineh & Farzad Mokhtari

  2. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Behafarid Ghalandari

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  1. Ali Dadras
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Correspondence to Gholam Hossein Riazi.

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Dadras, A., Riazi, G.H., Afrasiabi, A. et al. In vitro study on the alterations of brain tubulin structure and assembly affected by magnetite nanoparticles. J Biol Inorg Chem 18, 357–369 (2013). https://doi.org/10.1007/s00775-013-0980-x

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