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CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy
Human mesenchymal stem cells (hMSCs) are widely used in regenerative medicine. In some applications, they must survive under low nutrient conditions engendered by avascularity. Strategies to improve hMSCs survival may be of high relevance in tissue engineering. Carnitine palmitoyltransferase 1 C (CP...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934389/ https://www.ncbi.nlm.nih.gov/pubmed/29725060 http://dx.doi.org/10.1038/s41598-018-25485-7 |
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author | Roa-Mansergas, Xavier Fadó, Rut Atari, Maher Mir, Joan F. Muley, Helena Serra, Dolors Casals, Núria |
author_facet | Roa-Mansergas, Xavier Fadó, Rut Atari, Maher Mir, Joan F. Muley, Helena Serra, Dolors Casals, Núria |
author_sort | Roa-Mansergas, Xavier |
collection | PubMed |
description | Human mesenchymal stem cells (hMSCs) are widely used in regenerative medicine. In some applications, they must survive under low nutrient conditions engendered by avascularity. Strategies to improve hMSCs survival may be of high relevance in tissue engineering. Carnitine palmitoyltransferase 1 C (CPT1C) is a pseudoenzyme exclusively expressed in neurons and cancer cells. In the present study, we show that CPT1C is also expressed in hMSCs and protects them against glucose starvation, glycolysis inhibition, and oxygen/glucose deprivation. CPT1C overexpression in hMSCs did not increase fatty acid oxidation capacity, indicating that the role of CPT1C in these cells is different from that described in tumor cells. The increased survival of CPT1C-overexpressing hMSCs observed during glucose deficiency was found to be the result of autophagy enhancement, leading to a greater number of lipid droplets and increased intracellular ATP levels. In fact, inhibition of autophagy or lipolysis was observed to completely block the protective effects of CPT1C. Our results indicate that CPT1C-mediated autophagy enhancement in glucose deprivation conditions allows a greater availability of lipids to be used as fuel substrate for ATP generation, revealing a new role of CPT1C in stem cell adaptation to low nutrient environments. |
format | Online Article Text |
id | pubmed-5934389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59343892018-05-10 CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy Roa-Mansergas, Xavier Fadó, Rut Atari, Maher Mir, Joan F. Muley, Helena Serra, Dolors Casals, Núria Sci Rep Article Human mesenchymal stem cells (hMSCs) are widely used in regenerative medicine. In some applications, they must survive under low nutrient conditions engendered by avascularity. Strategies to improve hMSCs survival may be of high relevance in tissue engineering. Carnitine palmitoyltransferase 1 C (CPT1C) is a pseudoenzyme exclusively expressed in neurons and cancer cells. In the present study, we show that CPT1C is also expressed in hMSCs and protects them against glucose starvation, glycolysis inhibition, and oxygen/glucose deprivation. CPT1C overexpression in hMSCs did not increase fatty acid oxidation capacity, indicating that the role of CPT1C in these cells is different from that described in tumor cells. The increased survival of CPT1C-overexpressing hMSCs observed during glucose deficiency was found to be the result of autophagy enhancement, leading to a greater number of lipid droplets and increased intracellular ATP levels. In fact, inhibition of autophagy or lipolysis was observed to completely block the protective effects of CPT1C. Our results indicate that CPT1C-mediated autophagy enhancement in glucose deprivation conditions allows a greater availability of lipids to be used as fuel substrate for ATP generation, revealing a new role of CPT1C in stem cell adaptation to low nutrient environments. Nature Publishing Group UK 2018-05-03 /pmc/articles/PMC5934389/ /pubmed/29725060 http://dx.doi.org/10.1038/s41598-018-25485-7 Text en © The Author(s) 2018 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 Roa-Mansergas, Xavier Fadó, Rut Atari, Maher Mir, Joan F. Muley, Helena Serra, Dolors Casals, Núria CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy |
title | CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy |
title_full | CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy |
title_fullStr | CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy |
title_full_unstemmed | CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy |
title_short | CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy |
title_sort | cpt1c promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934389/ https://www.ncbi.nlm.nih.gov/pubmed/29725060 http://dx.doi.org/10.1038/s41598-018-25485-7 |
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