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Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity
Both the absence of cyclophilin D (CypD) and the presence of mitochondrial bound hexokinase II (mtHKII) protect the heart against ischemia/reperfusion (I/R) injury. It is unknown whether CypD determines the amount of mtHKII in the heart. We examined whether CypD affects mtHK in normoxic, ischemic an...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630626/ https://www.ncbi.nlm.nih.gov/pubmed/28986541 http://dx.doi.org/10.1038/s41598-017-13096-7 |
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author | Nederlof, Rianne van den Elshout, Mark A. M. Koeman, Anneke Uthman, Laween Koning, Iris Eerbeek, Otto Weber, Nina C. Hollmann, Markus W. Zuurbier, Coert J. |
author_facet | Nederlof, Rianne van den Elshout, Mark A. M. Koeman, Anneke Uthman, Laween Koning, Iris Eerbeek, Otto Weber, Nina C. Hollmann, Markus W. Zuurbier, Coert J. |
author_sort | Nederlof, Rianne |
collection | PubMed |
description | Both the absence of cyclophilin D (CypD) and the presence of mitochondrial bound hexokinase II (mtHKII) protect the heart against ischemia/reperfusion (I/R) injury. It is unknown whether CypD determines the amount of mtHKII in the heart. We examined whether CypD affects mtHK in normoxic, ischemic and preconditioned isolated mouse hearts. Wild type (WT) and CypD(−/−) mouse hearts were perfused with glucose only and subjected to 25 min ischemia and reperfusion. At baseline, cytosolic and mtHK was similar between hearts. CypD ablation protected against I/R injury and increased ischemic preconditioning (IPC) effects, without affecting end-ischemic mtHK. When hearts were perfused with glucose, glutamine, pyruvate and lactate, the preparation was more stable and CypD ablation(−)resulted in more protection that was associated with increased mtHK activity, leaving little room for additional protection by IPC. In conclusion, in glucose only-perfused hearts, deletion of CypD is not associated with end-ischemic mitochondrial-HK binding. In contrast, in the physiologically more relevant multiple-substrate perfusion model, deletion of CypD is associated with an increased mtHK activity, possibly explaining the increased protection against I/R injury. |
format | Online Article Text |
id | pubmed-5630626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56306262017-10-17 Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity Nederlof, Rianne van den Elshout, Mark A. M. Koeman, Anneke Uthman, Laween Koning, Iris Eerbeek, Otto Weber, Nina C. Hollmann, Markus W. Zuurbier, Coert J. Sci Rep Article Both the absence of cyclophilin D (CypD) and the presence of mitochondrial bound hexokinase II (mtHKII) protect the heart against ischemia/reperfusion (I/R) injury. It is unknown whether CypD determines the amount of mtHKII in the heart. We examined whether CypD affects mtHK in normoxic, ischemic and preconditioned isolated mouse hearts. Wild type (WT) and CypD(−/−) mouse hearts were perfused with glucose only and subjected to 25 min ischemia and reperfusion. At baseline, cytosolic and mtHK was similar between hearts. CypD ablation protected against I/R injury and increased ischemic preconditioning (IPC) effects, without affecting end-ischemic mtHK. When hearts were perfused with glucose, glutamine, pyruvate and lactate, the preparation was more stable and CypD ablation(−)resulted in more protection that was associated with increased mtHK activity, leaving little room for additional protection by IPC. In conclusion, in glucose only-perfused hearts, deletion of CypD is not associated with end-ischemic mitochondrial-HK binding. In contrast, in the physiologically more relevant multiple-substrate perfusion model, deletion of CypD is associated with an increased mtHK activity, possibly explaining the increased protection against I/R injury. Nature Publishing Group UK 2017-10-06 /pmc/articles/PMC5630626/ /pubmed/28986541 http://dx.doi.org/10.1038/s41598-017-13096-7 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Nederlof, Rianne van den Elshout, Mark A. M. Koeman, Anneke Uthman, Laween Koning, Iris Eerbeek, Otto Weber, Nina C. Hollmann, Markus W. Zuurbier, Coert J. Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity |
title | Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity |
title_full | Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity |
title_fullStr | Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity |
title_full_unstemmed | Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity |
title_short | Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity |
title_sort | cyclophilin d ablation is associated with increased end-ischemic mitochondrial hexokinase activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630626/ https://www.ncbi.nlm.nih.gov/pubmed/28986541 http://dx.doi.org/10.1038/s41598-017-13096-7 |
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