Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease
Abstract
:1. Introduction
2. Results
2.1. The Levels of CLOCK and BMAL1 Are Elevated in Impaired Astrocytes on Cortex Region from Patients with Alzheimer’s Disease
2.2. The Elevation of CLOCK and BMAL1 Suppresses Aerobic Glycolysis and Lactate Production by Reduction in HK1 and LDHA Protein Levels in Human Astrocytes
2.3. The Elevation of CLOCK and BMAL1 Contributes to the Functional Impairment by Reduction in GFAP-Positive Filaments in Human Astrocytes
2.4. The Elevation of CLOCK and BMAL1 Induces Cytotoxicity in Human Astrocytes
2.5. The Elevation of CLOCK and BMAL1 Induces Caspase-3-Dependent Apoptosis in Human Astrocytes
3. Discussion
4. Materials and Methods
4.1. Human Subject Study
4.2. Reagents and Antibodies
4.3. Human Astrocytes
4.4. Immunofluorescence Analysis
4.5. Glycolysis Activity Assay
4.6. 3D Images
4.7. Immunoblot Analysis
4.8. Cell Cytotoxicity Assay
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
CLOCK | Circadian locomotor output cycles kaput |
BMAL1 | Brain muscle ARNT-like1 |
AD | Alzheimer’s disease |
HK1 | Hexokinase 1 |
LDHA | Lactate dehydrogenase A |
ECAR | Extracellular acidification rate |
GFAP | Glial fibrillary acidic protein |
BBB | Blood–Brain barrier |
CNS | Central nervous system |
2-DG | 2-Deoxyglucose |
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Yoo, I.D.; Park, M.W.; Cha, H.W.; Yoon, S.; Boonpraman, N.; Yi, S.S.; Moon, J.-S. Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease. Int. J. Mol. Sci. 2020, 21, 7862. https://doi.org/10.3390/ijms21217862
Yoo ID, Park MW, Cha HW, Yoon S, Boonpraman N, Yi SS, Moon J-S. Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease. International Journal of Molecular Sciences. 2020; 21(21):7862. https://doi.org/10.3390/ijms21217862
Chicago/Turabian StyleYoo, Ik Dong, Min Woo Park, Hyeon Woo Cha, Sunmi Yoon, Napissara Boonpraman, Sun Shin Yi, and Jong-Seok Moon. 2020. "Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease" International Journal of Molecular Sciences 21, no. 21: 7862. https://doi.org/10.3390/ijms21217862