Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization
Abstract
:1. Introduction
2. Results
2.1. Homocysteine Reduces Tau Turnover
2.2. Homocysteine Increases Phosphorylated Tau
2.3. Homocysteine Treatment Activates Caspase 3 and Increases C-Terminal Truncated Tau
2.4. Temporal Profile of Phosphorylated Tau and Caspase-Cleaved Tau Following Homocysteine Treatment
2.5. Homocysteine Increases Sarkosyl Insoluble Tau and Oligomeric Tau
2.6. Homocysteine Induces Cell Death
2.7. Homocysteine Induces Endogenous Tau Accumulation
2.8. Induction of Hyperhomocysteinema in P301L Mice Increased Tau Phosphorylation, Cleavage and Oligomerization, an Effect Reversed by S-Adnosylmethionine Supplementation
2.9. Tau Accumulation Induced by Homocysteine Was Reversed by the Addition of Folic Acid
2.10. Hcy Treatment Inactivates the 20S Proteasome
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Antibodies
4.3. Cell Culture
4.4. Animals and Treatment
4.5. Fractionation Analysis
4.6. Western Blotting and Dot Blot
4.7. Immunocytochemistry
4.8. Morphological Study and Cell Viability Assay
4.9. mRNA Expression
4.10. Primary Neuronal Cell Culture
4.11. 20S Proteasome Activity Assay
4.12. Statistical Analysis
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
AD | Alzheimer’s disease |
HHCy | Hyperhomocysteinemia |
Hcy | Homocysteine |
SAH | S-adenosylhomocysteine |
SAM | S-adenosylmethionine |
cdk5 | cyclin-dependent kinase 5 |
PP2A | protein phosphatase 2A |
GSK3β | glycogen synthase kinase 3β |
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Shirafuji, N.; Hamano, T.; Yen, S.-H.; Kanaan, N.M.; Yoshida, H.; Hayashi, K.; Ikawa, M.; Yamamura, O.; Kuriyama, M.; Nakamoto, Y. Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization. Int. J. Mol. Sci. 2018, 19, 891. https://doi.org/10.3390/ijms19030891
Shirafuji N, Hamano T, Yen S-H, Kanaan NM, Yoshida H, Hayashi K, Ikawa M, Yamamura O, Kuriyama M, Nakamoto Y. Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization. International Journal of Molecular Sciences. 2018; 19(3):891. https://doi.org/10.3390/ijms19030891
Chicago/Turabian StyleShirafuji, Norimichi, Tadanori Hamano, Shu-Hui Yen, Nicholas M. Kanaan, Hirotaka Yoshida, Kouji Hayashi, Masamichi Ikawa, Osamu Yamamura, Masaru Kuriyama, and Yasunari Nakamoto. 2018. "Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization" International Journal of Molecular Sciences 19, no. 3: 891. https://doi.org/10.3390/ijms19030891