Hyperphosphorylation of Tau Due to the Interference of Protein Phosphatase Methylesterase-1 Overexpression by MiR-125b-5p in Melatonin Receptor Knockout Mice
Abstract
:1. Introduction
2. Results
2.1. Melatonin Receptor Knockout Mice Exhibit a Strong Signal for Hypophosphorylated Tau
2.2. Tau Hyperphosphorylation Is Caused by the Decreased Activity of PP2A
2.3. The Melatonin Receptor Regulates PP2A through PME-1
2.4. cAMP Promotes the Transcription of PME-1 by Decreasing the Production of miR-125b-5p
2.5. Decreased miR-125b-5p Induces Tau Hyperphosphorylation
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Antibodies
4.3. Western Blot
4.4. Cell Culture and Treatments
4.5. Immunohistochemistry
4.6. PP2A Activity Assay
4.7. Bielschowsky Silver Staining and Analysis
4.8. cAMP ELISA
4.9. RNA Isolation and Real-Time PCR
4.10. Luciferase-Reporter Plasmid Construction and Transfection
4.11. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Gene Name | RT Oligonucleotide | qPCR Forward Primer | qPCR Reverse Primer |
---|---|---|---|
MiR-125b-5p | CACCGTTCCCCGCCGTCGGTGTCACAA | GCCTCCCTGAGACCCTA | CCGTCGGTGTCACAAGTTAG |
SnoU6 | CACCGTTCCCCGCCGTCGGTGCTTCTC | CTCGCTTCGGCAGCA | GCCGTCGGTGCTTCTCTGT |
Ppme1 | TCAAATGTCTTCCCAGGCTCAG | CCACCGCTCGCTATGGCTAA | |
β-actin | GTCGTACCACAGGCATTGTGTGG | GCAATGCCTGGGTACATGGTGG |
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Zhao, H.; Feng, L.; Zhong, W.; Zhen, H.; Chi, Q.; Wang, X. Hyperphosphorylation of Tau Due to the Interference of Protein Phosphatase Methylesterase-1 Overexpression by MiR-125b-5p in Melatonin Receptor Knockout Mice. Int. J. Mol. Sci. 2021, 22, 11850. https://doi.org/10.3390/ijms222111850
Zhao H, Feng L, Zhong W, Zhen H, Chi Q, Wang X. Hyperphosphorylation of Tau Due to the Interference of Protein Phosphatase Methylesterase-1 Overexpression by MiR-125b-5p in Melatonin Receptor Knockout Mice. International Journal of Molecular Sciences. 2021; 22(21):11850. https://doi.org/10.3390/ijms222111850
Chicago/Turabian StyleZhao, Han, Lingyan Feng, Wei Zhong, Hongyan Zhen, Qingjia Chi, and Xiang Wang. 2021. "Hyperphosphorylation of Tau Due to the Interference of Protein Phosphatase Methylesterase-1 Overexpression by MiR-125b-5p in Melatonin Receptor Knockout Mice" International Journal of Molecular Sciences 22, no. 21: 11850. https://doi.org/10.3390/ijms222111850