α-synuclein interaction with zero-valent iron nanoparticles accelerates structural rearrangement into amyloid-susceptible structure with increased cytotoxic tendency
Seyedeh Sahar Tahaei Gilan,1,* Dorsa Yahya Rayat,1,* Twana Ahmed Mustafa,2 Falah Mohammad Aziz,3 Koorosh Shahpasand,4 Keivan Akhtari,5 Abbas Salihi,3,6 Osama K Abou-Zied,7 Mojtaba Falahati81Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Scien...
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| Autores principales: | , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2019
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| Acceso en línea: | https://doaj.org/article/091d5c5a18754146ac2b7bbb88e4a329 |
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| Sumario: | Seyedeh Sahar Tahaei Gilan,1,* Dorsa Yahya Rayat,1,* Twana Ahmed Mustafa,2 Falah Mohammad Aziz,3 Koorosh Shahpasand,4 Keivan Akhtari,5 Abbas Salihi,3,6 Osama K Abou-Zied,7 Mojtaba Falahati81Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 2Department of Medical Laboratory Technology, Health Technical College, Erbil Polytechnic University, Erbil, Kurdistan Region, Iraq; 3Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq; 4Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; 5Department of Physics, University of Kurdistan, Sanandaj, Iran; 6Department of Medical Analysis, Faculty of Science, Tishk International University, Erbil, Iraq; 7Department of Chemistry, Faculty of Science, Sultan Qaboos University, P.O. Box 36, Postal Code 123 Muscat, Oman; 8Department of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran*These authors contributed equally to this workAim: It has been indicated that NPs may change the amyloidogenic steps of proteins and relevant cytotoxicity. Therefore, this report assigned to explore the impact of ZVFe NPs on the amyloidogenicity and cytotoxicity of α-synuclein as one of the many known amyloid proteins.Methods: The characterization of α-synuclein at amyloidogenic condition either alone or with ZVFe NPs was carried out by fluorescence, CD, UV-visible spectroscopic methods, TEM study, docking, and molecular modeling. The cytotoxicity assay of α-synuclein amyloid in the absence and presence of ZVFe NPs was also done by MTT, LDH, and flow cytometry analysis.Results: ThT fluorescence spectroscopy revealed that ZVFe NPs shorten the lag phase and accelerate the fibrillation rate of α-synuclein. Nile red and intrinsic fluorescence spectroscopy, CD, Congo red adsorption, and TEM studies indicated that ZVFe NP increased the propensity of α-synuclein into the amyloid fibrillation. Molecular docking study revealed that hydrophilic residues, such as Ser-9 and Lys-12 provide proper sites for hydrogen bonding and electrostatic interactions with adsorbed water molecules on ZVFe NPs, respectively. Molecular dynamics study determined that the interacted protein shifted from a natively discorded conformation toward a more packed structure. Cellular assay displayed that the cytotoxicity of α-synuclein amyloid against SH-SY5Y cells in the presence of ZVFe NPs is greater than the results obtained without ZVFe NPs.Conclusion: In conclusion, the existence of ZVFe NPs promotes α-synuclein fibrillation at amyloidogenic conditions by forming a potential template for nucleation, the growth of α-synuclein fibrillation and induced cytotoxicity.Keywords: α-synuclein, ZVFe NP, amyloid, cytotoxicity, spectroscopy |
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