Possible Role of Interaction between PPARα and Cyclophilin D in Cardioprotection of AMPK against In Vivo Ischemia-Reperfusion in Rats
Activated AMPK protects the heart from cardiac ischemia-reperfusion (IR) injury and is associated with inhibition of mitochondrial permeability transition pore (PTP) opening. On the other hand, pharmacological inhibition of the PTP reduces infarct size and improves cardiac function. However, it is u...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2016/9282087 |
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| author | Giselle Barreto-Torres Sabzali Javadov |
| author_facet | Giselle Barreto-Torres Sabzali Javadov |
| author_sort | Giselle Barreto-Torres |
| collection | DOAJ |
| description | Activated AMPK protects the heart from cardiac ischemia-reperfusion (IR) injury and is associated with inhibition of mitochondrial permeability transition pore (PTP) opening. On the other hand, pharmacological inhibition of the PTP reduces infarct size and improves cardiac function. However, it is unclear whether beneficial effects of AMPK are mediated through the PTP and, if they are not, whether simultaneous activation of AMPK and inhibition of the PTP exert synergistic protective effects against cardiac IR injury. Here, we examined the effects of the AMPK activator, A-769662 in combination with the PTP inhibitor, sanglifehrin A (SfA) on in vivo cardiac IR. Cardiac dysfunction following IR injury was associated with decreased activity of the mitochondrial electron transport chain (ETC) and increased mitochondrial ROS and PTP opening. Administration of A-769662 or SfA individually upon reperfusion improved cardiac function, reduced infarction size, and inhibited ROS production and PTP opening. However, simultaneous administration of SfA and A-769662 did not provide synergistic improvement of postischemic recovery of cardiac and mitochondrial function, though both compounds disrupted IR-induced interaction between PPARα and CyP-D. In conclusion, A-769662 or SfA prevents PPARα interaction with CyP-D, improving cardiac outcomes and increasing mitochondrial function, and simultaneous administration of the drugs does not provide synergistic effects. |
| format | Article |
| id | doaj-art-fb8fa42a474a49ebb285e8885d1fc9bd |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-fb8fa42a474a49ebb285e8885d1fc9bd2025-02-03T05:54:04ZengWileyPPAR Research1687-47571687-47652016-01-01201610.1155/2016/92820879282087Possible Role of Interaction between PPARα and Cyclophilin D in Cardioprotection of AMPK against In Vivo Ischemia-Reperfusion in RatsGiselle Barreto-Torres0Sabzali Javadov1Department of Physiology, University of Puerto Rico School of Medicine, San Juan, PR 00936-5067, USADepartment of Physiology, University of Puerto Rico School of Medicine, San Juan, PR 00936-5067, USAActivated AMPK protects the heart from cardiac ischemia-reperfusion (IR) injury and is associated with inhibition of mitochondrial permeability transition pore (PTP) opening. On the other hand, pharmacological inhibition of the PTP reduces infarct size and improves cardiac function. However, it is unclear whether beneficial effects of AMPK are mediated through the PTP and, if they are not, whether simultaneous activation of AMPK and inhibition of the PTP exert synergistic protective effects against cardiac IR injury. Here, we examined the effects of the AMPK activator, A-769662 in combination with the PTP inhibitor, sanglifehrin A (SfA) on in vivo cardiac IR. Cardiac dysfunction following IR injury was associated with decreased activity of the mitochondrial electron transport chain (ETC) and increased mitochondrial ROS and PTP opening. Administration of A-769662 or SfA individually upon reperfusion improved cardiac function, reduced infarction size, and inhibited ROS production and PTP opening. However, simultaneous administration of SfA and A-769662 did not provide synergistic improvement of postischemic recovery of cardiac and mitochondrial function, though both compounds disrupted IR-induced interaction between PPARα and CyP-D. In conclusion, A-769662 or SfA prevents PPARα interaction with CyP-D, improving cardiac outcomes and increasing mitochondrial function, and simultaneous administration of the drugs does not provide synergistic effects.http://dx.doi.org/10.1155/2016/9282087 |
| spellingShingle | Giselle Barreto-Torres Sabzali Javadov Possible Role of Interaction between PPARα and Cyclophilin D in Cardioprotection of AMPK against In Vivo Ischemia-Reperfusion in Rats PPAR Research |
| title | Possible Role of Interaction between PPARα and Cyclophilin D in Cardioprotection of AMPK against In Vivo Ischemia-Reperfusion in Rats |
| title_full | Possible Role of Interaction between PPARα and Cyclophilin D in Cardioprotection of AMPK against In Vivo Ischemia-Reperfusion in Rats |
| title_fullStr | Possible Role of Interaction between PPARα and Cyclophilin D in Cardioprotection of AMPK against In Vivo Ischemia-Reperfusion in Rats |
| title_full_unstemmed | Possible Role of Interaction between PPARα and Cyclophilin D in Cardioprotection of AMPK against In Vivo Ischemia-Reperfusion in Rats |
| title_short | Possible Role of Interaction between PPARα and Cyclophilin D in Cardioprotection of AMPK against In Vivo Ischemia-Reperfusion in Rats |
| title_sort | possible role of interaction between pparα and cyclophilin d in cardioprotection of ampk against in vivo ischemia reperfusion in rats |
| url | http://dx.doi.org/10.1155/2016/9282087 |
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