Rosiglitazone Protects Endothelial Cells From Irradiation-Induced Mitochondrial Dysfunction
Background and PurposeUp to 50–60% of all cancer patients receive radiotherapy as part of their treatment strategy. However, the mechanisms accounting for increased vascular risks after irradiation are not completely understood. Mitochondrial dysfunction has been identified as a potential cause of r...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00268/full |
| _version_ | 1818967159158603776 |
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| author | Bjorn Baselet Bjorn Baselet Ronald B. Driesen Emma Coninx Emma Coninx Niels Belmans Niels Belmans Tom Sieprath Ivo Lambrichts Winnok H. De Vos Winnok H. De Vos Sarah Baatout Sarah Baatout Pierre Sonveaux An Aerts |
| author_facet | Bjorn Baselet Bjorn Baselet Ronald B. Driesen Emma Coninx Emma Coninx Niels Belmans Niels Belmans Tom Sieprath Ivo Lambrichts Winnok H. De Vos Winnok H. De Vos Sarah Baatout Sarah Baatout Pierre Sonveaux An Aerts |
| author_sort | Bjorn Baselet |
| collection | DOAJ |
| description | Background and PurposeUp to 50–60% of all cancer patients receive radiotherapy as part of their treatment strategy. However, the mechanisms accounting for increased vascular risks after irradiation are not completely understood. Mitochondrial dysfunction has been identified as a potential cause of radiation-induced atherosclerosis.Materials and MethodsAssays for apoptosis, cellular metabolism, mitochondrial DNA content, functionality and morphology were used to compare the response of endothelial cells to a single 2 Gy dose of X-rays under basal conditions or after pharmacological treatments that either reduced (EtBr) or increased (rosiglitazone) mitochondrial content.ResultsExposure to ionizing radiation caused a persistent reduction in mitochondrial content of endothelial cells. Pharmacological reduction of mitochondrial DNA content rendered endothelial cells more vulnerable to radiation-induced apoptosis, whereas rosiglitazone treatment increased oxidative metabolism and redox state and decreased the levels of apoptosis after irradiation.ConclusionPre-existing mitochondrial damage sensitizes endothelial cells to ionizing radiation-induced mitochondrial dysfunction. Rosiglitazone protects endothelial cells from the detrimental effects of radiation exposure on mitochondrial metabolism and oxidative stress. Thus, our findings indicate that rosiglitazone may have potential value as prophylactic for radiation-induced atherosclerosis. |
| first_indexed | 2024-12-20T13:44:22Z |
| format | Article |
| id | doaj.art-5af9740453394502a0c2b8d60c6bce20 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T13:44:22Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-5af9740453394502a0c2b8d60c6bce202022-12-21T19:38:43ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-03-011110.3389/fphar.2020.00268506877Rosiglitazone Protects Endothelial Cells From Irradiation-Induced Mitochondrial DysfunctionBjorn Baselet0Bjorn Baselet1Ronald B. Driesen2Emma Coninx3Emma Coninx4Niels Belmans5Niels Belmans6Tom Sieprath7Ivo Lambrichts8Winnok H. De Vos9Winnok H. De Vos10Sarah Baatout11Sarah Baatout12Pierre Sonveaux13An Aerts14Institute for Environment, Health and Safety, Radiobiology Unit, Belgian Nuclear Research Centre (SCK CEN), Mol, BelgiumInstitute of Experimental and Clinical Research (IREC), Pole of Pharmacology and Therapeutics, Université catholique de Louvain (UCLouvain), Brussels, BelgiumLaboratory of Morphology, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, BelgiumInstitute for Environment, Health and Safety, Radiobiology Unit, Belgian Nuclear Research Centre (SCK CEN), Mol, BelgiumNeural Circuit Development and Regeneration Research Group, KU Leuven, Leuven, BelgiumInstitute for Environment, Health and Safety, Radiobiology Unit, Belgian Nuclear Research Centre (SCK CEN), Mol, BelgiumFaculty of Medicine and Life Sciences, Biomedical Research Institute, Hasselt University, Hasselt, BelgiumCell Systems and Imaging Research Group (CSI), Department of Molecular Biotechnology, Ghent University, Ghent, BelgiumLaboratory of Morphology, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, BelgiumCell Systems and Imaging Research Group (CSI), Department of Molecular Biotechnology, Ghent University, Ghent, BelgiumLaboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, BelgiumInstitute for Environment, Health and Safety, Radiobiology Unit, Belgian Nuclear Research Centre (SCK CEN), Mol, BelgiumDepartment of Molecular Biotechnology, Ghent University, Ghent, BelgiumInstitute of Experimental and Clinical Research (IREC), Pole of Pharmacology and Therapeutics, Université catholique de Louvain (UCLouvain), Brussels, BelgiumInstitute for Environment, Health and Safety, Radiobiology Unit, Belgian Nuclear Research Centre (SCK CEN), Mol, BelgiumBackground and PurposeUp to 50–60% of all cancer patients receive radiotherapy as part of their treatment strategy. However, the mechanisms accounting for increased vascular risks after irradiation are not completely understood. Mitochondrial dysfunction has been identified as a potential cause of radiation-induced atherosclerosis.Materials and MethodsAssays for apoptosis, cellular metabolism, mitochondrial DNA content, functionality and morphology were used to compare the response of endothelial cells to a single 2 Gy dose of X-rays under basal conditions or after pharmacological treatments that either reduced (EtBr) or increased (rosiglitazone) mitochondrial content.ResultsExposure to ionizing radiation caused a persistent reduction in mitochondrial content of endothelial cells. Pharmacological reduction of mitochondrial DNA content rendered endothelial cells more vulnerable to radiation-induced apoptosis, whereas rosiglitazone treatment increased oxidative metabolism and redox state and decreased the levels of apoptosis after irradiation.ConclusionPre-existing mitochondrial damage sensitizes endothelial cells to ionizing radiation-induced mitochondrial dysfunction. Rosiglitazone protects endothelial cells from the detrimental effects of radiation exposure on mitochondrial metabolism and oxidative stress. Thus, our findings indicate that rosiglitazone may have potential value as prophylactic for radiation-induced atherosclerosis.https://www.frontiersin.org/article/10.3389/fphar.2020.00268/fullionizing radiationendothelial cellsrosiglitazonemitochondriacardiovascular disease |
| spellingShingle | Bjorn Baselet Bjorn Baselet Ronald B. Driesen Emma Coninx Emma Coninx Niels Belmans Niels Belmans Tom Sieprath Ivo Lambrichts Winnok H. De Vos Winnok H. De Vos Sarah Baatout Sarah Baatout Pierre Sonveaux An Aerts Rosiglitazone Protects Endothelial Cells From Irradiation-Induced Mitochondrial Dysfunction Frontiers in Pharmacology ionizing radiation endothelial cells rosiglitazone mitochondria cardiovascular disease |
| title | Rosiglitazone Protects Endothelial Cells From Irradiation-Induced Mitochondrial Dysfunction |
| title_full | Rosiglitazone Protects Endothelial Cells From Irradiation-Induced Mitochondrial Dysfunction |
| title_fullStr | Rosiglitazone Protects Endothelial Cells From Irradiation-Induced Mitochondrial Dysfunction |
| title_full_unstemmed | Rosiglitazone Protects Endothelial Cells From Irradiation-Induced Mitochondrial Dysfunction |
| title_short | Rosiglitazone Protects Endothelial Cells From Irradiation-Induced Mitochondrial Dysfunction |
| title_sort | rosiglitazone protects endothelial cells from irradiation induced mitochondrial dysfunction |
| topic | ionizing radiation endothelial cells rosiglitazone mitochondria cardiovascular disease |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00268/full |
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