Vitamin K1 As A Potential Molecule For Reducing Single-Walled Carbon Nanotubes-Stimulated α-Synuclein Structural Changes And Cytotoxicity

Amitis Naskhi,1,* Sanaz Jabbari,1,* Goran Qader Othman,2 Falah Mohammad Aziz,3 Abbas Salihi,3,4 Majid Sharifi,5 Soyar Sari,1 Keivan Akhtari,6 Shang Ziyad Abdulqadir,3 Asaad AB Alasady,7 Osama K Abou-Zied,8 Anwarul Hasan,9,10 Mojtaba Falahati5 1Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 2Department of Medical Laboratory, Health Technical College, Erbil Polytechnique University, Erbil, Iraq; 3Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq; 4Department of Medical Analysis, Faculty of Science, Tishk International University, Erbil, Iraq; 5Department of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 6Department of Physics, University of Kurdistan, Sanandaj, Iran; 7Anatomy, Histology, and Embryology Unit, College of Medicine, University of Duhok, Kurdistan Region, Iraq; 8Department of Chemistry, Faculty of Science, Sultan Qaboos University, Muscat, Sultanate of Oman; 9Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, Qatar; 10Biomedical Research Center, Qatar University, Doha 2713, Qatar*These authors contributed equally to this workCorrespondence: Mojtaba FalahatiDepartment of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, IranEmail mojtaba.falahati@alumni.ut.ac.irAnwarul HasanDepartment of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, QatarEmail hasan.anwarul.mit@gmail.comAims: Different kinds of vitamins can be used as promising candidates to mitigate the structural changes of proteins and associated cytotoxicity stimulated by NPs. Therefore, the structural changes of α-syn molecules and their associated cytotoxicity in the presence of SWCNTs either alone or co-incubated with vitamin K1 were studied by spectroscopic, bioinformatical, and cellular assays.Methods: Intrinsic and ThT fluorescence, CD, and Congo red absorption spectroscopic approaches as well as TEM investigation, molecular docking, and molecular dynamics were used to explore the protective effect of vitamin K1 on the structural changes of α-syn induced by SWCNTs. The cytotoxicity of α-syn/SWCNTs co-incubated with vitamin K1 against SH-SY5Y cells was also carried out by MTT, LDH, and caspase-3 assays.Results: Fluorescence spectroscopy showed that vitamin K1 has a significant effect in reducing SWCNT-induced fluorescence quenching and aggregation of α- syn. CD, Congo red adsorption, and TEM investigations determined that co-incubation of α- syn with vitamin K1 inhibited the propensity of α-syn into the structural changes and amorphous aggregation in the presence of SWCNT. Docking studies determined the occupation of preferred docked site of SWCNT by vitamin K1 on α- syn conformation. A molecular dynamics study also showed that vitamin K1 reduced the structural changes of α- syn induced by SWCNT. Cellular data exhibited that the cytotoxicity of α- syn co-incubated with vitamin K1 in the presence of SWCNTs is less than the outcomes obtained in the absence of the vitamin K1.Conclusion: It may be concluded that vitamin K1 decreases the propensity of α- syn aggregation in the presence of SWCNTs and induction of cytotoxicity.Keywords: α- Syn, single-walled carbon nanotube, aggregation, vitamin K1, cytotoxicity