The Antibiotic Doxycycline Impairs Cardiac Mitochondrial and Contractile Function
Abstract
:1. Introduction
2. Results
2.1. Mitonuclear Protein Imbalance in Doxycycline-Treated Cardiac Cells
2.2. Maximal Mitochondrial Respiration Is Lower in Doxycycline-Treated Cardiac Cells
2.3. Doxycycline Reduced Both Complex I- and Complex II-Driven Respiration in Cardiac Cells
2.4. Doxycycline-Treated Cardiomyocytes Shift Away from Oxphos towards Glycolysis
2.5. Mitochondria Appear Fragmented In Doxycycline-Treated Cardiac Cells
2.6. Doxycycline-Treated Adult Rat Cardiomyocytes Have Higher Diastolic Calcium and More Irregular Calcium Waves
2.7. Doxycycline Exposure Causes Contractile Dysfunction in Drosophila Melanogaster Hearts
2.8. Doxycycline Exposure Reduces Mitochondrial Respiration and Results in Contractile Dysfunction in Mice, Particularly in Diabetic Animals
3. Discussion
4. Materials and Methods
4.1. Cells
4.2. Western Immunoblotting
4.3. Mitochondrial Respiration
4.4. Complex I and II-Stimulated Respiration
4.5. Live-Cell Imaging
4.6. Substrate Flux Analysis
4.7. Myocyte Isolation and Cytosolic Ca2+ Measurements
4.8. Drosophila Melanogaster Stocks and Heart Wall Measurements
4.9. Mice
4.10. In Vivo Systolic and Diastolic Function
4.11. Mitochondrial Respiration in Doxycycline-Treated Mice
4.12. Blood Parameters
4.13. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Wüst, R.C.I.; Coolen, B.F.; Held, N.M.; Daal, M.R.R.; Alizadeh Tazehkandi, V.; Baks-te Bulte, L.; Wiersma, M.; Kuster, D.W.D.; Brundel, B.J.J.M.; van Weeghel, M.; et al. The Antibiotic Doxycycline Impairs Cardiac Mitochondrial and Contractile Function. Int. J. Mol. Sci. 2021, 22, 4100. https://doi.org/10.3390/ijms22084100
Wüst RCI, Coolen BF, Held NM, Daal MRR, Alizadeh Tazehkandi V, Baks-te Bulte L, Wiersma M, Kuster DWD, Brundel BJJM, van Weeghel M, et al. The Antibiotic Doxycycline Impairs Cardiac Mitochondrial and Contractile Function. International Journal of Molecular Sciences. 2021; 22(8):4100. https://doi.org/10.3390/ijms22084100
Chicago/Turabian StyleWüst, Rob C. I., Bram F. Coolen, Ntsiki M. Held, Mariah R. R. Daal, Vida Alizadeh Tazehkandi, Luciënne Baks-te Bulte, Marit Wiersma, Diederik W. D. Kuster, Bianca J. J. M. Brundel, Michel van Weeghel, and et al. 2021. "The Antibiotic Doxycycline Impairs Cardiac Mitochondrial and Contractile Function" International Journal of Molecular Sciences 22, no. 8: 4100. https://doi.org/10.3390/ijms22084100
APA StyleWüst, R. C. I., Coolen, B. F., Held, N. M., Daal, M. R. R., Alizadeh Tazehkandi, V., Baks-te Bulte, L., Wiersma, M., Kuster, D. W. D., Brundel, B. J. J. M., van Weeghel, M., Strijkers, G. J., & Houtkooper, R. H. (2021). The Antibiotic Doxycycline Impairs Cardiac Mitochondrial and Contractile Function. International Journal of Molecular Sciences, 22(8), 4100. https://doi.org/10.3390/ijms22084100