Cyclophilin D Regulates the Nuclear Translocation of AIF, Cardiac Endothelial Cell Necroptosis and Murine Cardiac Transplant Injury
Abstract
:1. Introduction
2. Results
2.1. In Vitro Simulation of Ischemia and Reperfusion Promotes Necroptosis in MVECs
2.2. CypD, Not ROS, Contributes to MVECs Necroptosis under In Vitro Simulating IRI Condition
2.3. AIF Translocates to the Nucleus during Necroptosis under In Vitro Simulation of IRI Conditions
2.4. CypD Deficiency in Donor Heart Graft Attenuates Graft IRI, AIF Translocation and Rejection
3. Discussion
4. Materials and Methods
4.1. Mice
4.2. Ethic Statement
4.3. In Vitro Cold Hypoxia and Warm Reoxygenation
4.4. RNA Interference
4.5. PCR
4.6. Western Blots
4.7. Immunocytochemistry
4.8. DNA Analysis
4.9. Cardiac Transplantation
4.10. Histology and Immunohistochemistry
4.11. Inclusion and Exclusion Criteria
4.12. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
3-ABA | 3-aminobanzamide |
BAX | Bcl-2-associated X. |
BID | Bcl-2 Homology 3-interacting domain death agonist. |
CsA | Cyclosporin A. |
CypD | Cyclophilin D. |
DAPI | Diamidino-2-phenylindole dihydrochloride |
MVEC | mouse microvascular endothelial cells. |
NAC | Nacetyl-L-cysteine. |
Nec-1s | Necrostatin-1s. |
PARP-1 | poly(ADP-ribose) polymerase 1 |
PCR | polymerase chain reaction. |
RIPK | receptor interacting protein kinase. |
ROS | reactive oxygen species. |
TEMPOL | tetramethylpiperidine-oxyl. |
Z-VAD-fmk | Z-Val-Ala-Asp-fluoromethylketoe. |
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Qamar, A.; Zhao, J.; Xu, L.; McLeod, P.; Huang, X.; Jiang, J.; Liu, W.; Haig, A.; Zhang, Z.-X. Cyclophilin D Regulates the Nuclear Translocation of AIF, Cardiac Endothelial Cell Necroptosis and Murine Cardiac Transplant Injury. Int. J. Mol. Sci. 2021, 22, 11038. https://doi.org/10.3390/ijms222011038
Qamar A, Zhao J, Xu L, McLeod P, Huang X, Jiang J, Liu W, Haig A, Zhang Z-X. Cyclophilin D Regulates the Nuclear Translocation of AIF, Cardiac Endothelial Cell Necroptosis and Murine Cardiac Transplant Injury. International Journal of Molecular Sciences. 2021; 22(20):11038. https://doi.org/10.3390/ijms222011038
Chicago/Turabian StyleQamar, Adnan, Jianqi Zhao, Laura Xu, Patrick McLeod, Xuyan Huang, Jifu Jiang, Weihua Liu, Aaron Haig, and Zhu-Xu Zhang. 2021. "Cyclophilin D Regulates the Nuclear Translocation of AIF, Cardiac Endothelial Cell Necroptosis and Murine Cardiac Transplant Injury" International Journal of Molecular Sciences 22, no. 20: 11038. https://doi.org/10.3390/ijms222011038