Extracellular Histone-Induced Protein Kinase C Alpha Activation and Troponin Phosphorylation Is a Potential Mechanism of Cardiac Contractility Depression in Sepsis
Abstract
:1. Introduction
2. Results
2.1. Histones Disturb Intracellular Calcium Dynamics
2.2. Histones Induce Ca2+-Dependent PKC Isoform Activation in Cardiomyocytes
2.3. Histones Enhance the Association of PKCα and PKCβII with Cardiac Myofilaments and Induce cTnI Phosphorylation
2.4. Histone-Induced cTnI Phosphorylation Is Mediated by PKCα and Contributes to Depressed Cardiomyocyte Contractility
2.5. Anti-Histone Antibody Abrogates Histone-Induced Activation of PKCα-cTnI Pathway to Rescue Cardiomyocyte Contractility
3. Discussion
4. Materials and Methods
4.1. HL-1 Cardiomyocyte Culture
4.2. Animal Experiments
4.3. Ca2+ Flux Measurement in HL-1 Cardiomyocytes
4.4. Measurement of HL-1 Cardiomyocytes Contractility
4.5. Whole Cell Lysates Preparation of HL-1 and Mouse Cardiomyocytes
4.6. Subcellular Fractionation of HL-1 and Mouse Cardiomyocytes
4.7. Western Blotting
4.8. Development of Anti-Histone Single Chain Variable Fragment Anti-Body (ahscFv)
4.9. Culture of Endothelial Cells
4.10. Statistics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Abrams, S.T.; Alhamdi, Y.; Zi, M.; Guo, F.; Du, M.; Wang, G.; Cartwright, E.J.; Toh, C.-H. Extracellular Histone-Induced Protein Kinase C Alpha Activation and Troponin Phosphorylation Is a Potential Mechanism of Cardiac Contractility Depression in Sepsis. Int. J. Mol. Sci. 2023, 24, 3225. https://doi.org/10.3390/ijms24043225
Abrams ST, Alhamdi Y, Zi M, Guo F, Du M, Wang G, Cartwright EJ, Toh C-H. Extracellular Histone-Induced Protein Kinase C Alpha Activation and Troponin Phosphorylation Is a Potential Mechanism of Cardiac Contractility Depression in Sepsis. International Journal of Molecular Sciences. 2023; 24(4):3225. https://doi.org/10.3390/ijms24043225
Chicago/Turabian StyleAbrams, Simon T., Yasir Alhamdi, Min Zi, Fengmei Guo, Min Du, Guozheng Wang, Elizabeth J. Cartwright, and Cheng-Hock Toh. 2023. "Extracellular Histone-Induced Protein Kinase C Alpha Activation and Troponin Phosphorylation Is a Potential Mechanism of Cardiac Contractility Depression in Sepsis" International Journal of Molecular Sciences 24, no. 4: 3225. https://doi.org/10.3390/ijms24043225