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Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism

Human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) are self-renewing human pluripotent stem cells (hPSCs) that can differentiate to a wide range of specialized cells. Notably, hPSCs enhance their undifferentiated state and self-renewal properties in hypoxia (5% O(2)). Although tho...

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Autores principales: Isaja, Luciana, Mucci, Sofía, Vera, Jonathan, Rodríguez-Varela, María Soledad, Marazita, Mariela, Morris-Hanon, Olivia, Videla-Richardson, Guillermo Agustín, Sevlever, Gustavo Emilio, Scassa, María Elida, Romorini, Leonardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692563/
https://www.ncbi.nlm.nih.gov/pubmed/33244167
http://dx.doi.org/10.1038/s41598-020-77792-7
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author Isaja, Luciana
Mucci, Sofía
Vera, Jonathan
Rodríguez-Varela, María Soledad
Marazita, Mariela
Morris-Hanon, Olivia
Videla-Richardson, Guillermo Agustín
Sevlever, Gustavo Emilio
Scassa, María Elida
Romorini, Leonardo
author_facet Isaja, Luciana
Mucci, Sofía
Vera, Jonathan
Rodríguez-Varela, María Soledad
Marazita, Mariela
Morris-Hanon, Olivia
Videla-Richardson, Guillermo Agustín
Sevlever, Gustavo Emilio
Scassa, María Elida
Romorini, Leonardo
author_sort Isaja, Luciana
collection PubMed
description Human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) are self-renewing human pluripotent stem cells (hPSCs) that can differentiate to a wide range of specialized cells. Notably, hPSCs enhance their undifferentiated state and self-renewal properties in hypoxia (5% O(2)). Although thoroughly analyzed, hypoxia implication in hPSCs death is not fully determined. In order to evaluate the effect of chemically mimicked hypoxia on hPSCs cell survival, we analyzed changes in cell viability and several aspects of apoptosis triggered by CoCl(2) and dimethyloxalylglycine (DMOG). Mitochondrial function assays revealed a decrease in cell viability at 24 h post-treatments. Moreover, we detected chromatin condensation, DNA fragmentation and CASPASE-9 and 3 cleavages. In this context, we observed that P53, BNIP-3, and NOXA protein expression levels were significantly up-regulated at different time points upon chemical hypoxia induction. However, only siRNA-mediated downregulation of NOXA but not HIF-1α, HIF-2α, BNIP-3, and P53 did significantly affect the extent of cell death triggered by CoCl(2) and DMOG in hPSCs. In conclusion, chemically mimicked hypoxia induces hPSCs cell death by a NOXA-mediated HIF-1α and HIF-2α independent mechanism.
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spelling pubmed-76925632020-11-30 Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism Isaja, Luciana Mucci, Sofía Vera, Jonathan Rodríguez-Varela, María Soledad Marazita, Mariela Morris-Hanon, Olivia Videla-Richardson, Guillermo Agustín Sevlever, Gustavo Emilio Scassa, María Elida Romorini, Leonardo Sci Rep Article Human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) are self-renewing human pluripotent stem cells (hPSCs) that can differentiate to a wide range of specialized cells. Notably, hPSCs enhance their undifferentiated state and self-renewal properties in hypoxia (5% O(2)). Although thoroughly analyzed, hypoxia implication in hPSCs death is not fully determined. In order to evaluate the effect of chemically mimicked hypoxia on hPSCs cell survival, we analyzed changes in cell viability and several aspects of apoptosis triggered by CoCl(2) and dimethyloxalylglycine (DMOG). Mitochondrial function assays revealed a decrease in cell viability at 24 h post-treatments. Moreover, we detected chromatin condensation, DNA fragmentation and CASPASE-9 and 3 cleavages. In this context, we observed that P53, BNIP-3, and NOXA protein expression levels were significantly up-regulated at different time points upon chemical hypoxia induction. However, only siRNA-mediated downregulation of NOXA but not HIF-1α, HIF-2α, BNIP-3, and P53 did significantly affect the extent of cell death triggered by CoCl(2) and DMOG in hPSCs. In conclusion, chemically mimicked hypoxia induces hPSCs cell death by a NOXA-mediated HIF-1α and HIF-2α independent mechanism. Nature Publishing Group UK 2020-11-26 /pmc/articles/PMC7692563/ /pubmed/33244167 http://dx.doi.org/10.1038/s41598-020-77792-7 Text en © The Author(s) 2020 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Isaja, Luciana
Mucci, Sofía
Vera, Jonathan
Rodríguez-Varela, María Soledad
Marazita, Mariela
Morris-Hanon, Olivia
Videla-Richardson, Guillermo Agustín
Sevlever, Gustavo Emilio
Scassa, María Elida
Romorini, Leonardo
Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism
title Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism
title_full Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism
title_fullStr Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism
title_full_unstemmed Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism
title_short Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism
title_sort chemical hypoxia induces apoptosis of human pluripotent stem cells by a noxa-mediated hif-1α and hif-2α independent mechanism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692563/
https://www.ncbi.nlm.nih.gov/pubmed/33244167
http://dx.doi.org/10.1038/s41598-020-77792-7
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