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Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma
Ceramide synthase 1 (CERS1) is the most highly expressed CERS in the central nervous system, and ceramide with an 18-carbon–containing fatty acid chain (C18-ceramide) in the brain plays important roles in signaling and sphingolipid development. However, the roles of CERS1 and C18-ceramide in glioma...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732784/ https://www.ncbi.nlm.nih.gov/pubmed/29262618 http://dx.doi.org/10.18632/oncotarget.21955 |
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author | Wang, Zheng Wen, Lijun Zhu, Fei Wang, Yanping Xie, Qing Chen, Zijun Li, Yunsen |
author_facet | Wang, Zheng Wen, Lijun Zhu, Fei Wang, Yanping Xie, Qing Chen, Zijun Li, Yunsen |
author_sort | Wang, Zheng |
collection | PubMed |
description | Ceramide synthase 1 (CERS1) is the most highly expressed CERS in the central nervous system, and ceramide with an 18-carbon–containing fatty acid chain (C18-ceramide) in the brain plays important roles in signaling and sphingolipid development. However, the roles of CERS1 and C18-ceramide in glioma are largely unknown. In the present study, measured by electrospray ionization linear ion trap mass spectrometry, C18-ceramide was significantly lower in glioma tumor tissues compared with controls (P < 0.001), indicating that C18-ceramide might have a role in glioma. These roles were examined by reconstitution of C18-ceramide in U251 and A172 glioma cells via addition of exogenous C18-ceramide or overexpression of CERS1, which has been shown to specifically induce the generation of C18-ceramide. Overexpression of CERS1 or adding exogenous C18-ceramide inhibited cell viability and induced cell death by activating endoplasmic reticulum stress, which induced lethal autophagy and inhibited PI3K/AKT signal pathway in U251 and A172 glioma cells. Moreover, overexpression of CERS1 or adding exogenous C18-ceramide increased the sensitivity of U251 and A172 glioma cells to teniposide (VM-26). Thus, the combined therapy of CERS1/C18-ceramide and VM-26 may be a novel therapeutic strategy for the treatment of human glioma. |
format | Online Article Text |
id | pubmed-5732784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57327842017-12-19 Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma Wang, Zheng Wen, Lijun Zhu, Fei Wang, Yanping Xie, Qing Chen, Zijun Li, Yunsen Oncotarget Research Paper Ceramide synthase 1 (CERS1) is the most highly expressed CERS in the central nervous system, and ceramide with an 18-carbon–containing fatty acid chain (C18-ceramide) in the brain plays important roles in signaling and sphingolipid development. However, the roles of CERS1 and C18-ceramide in glioma are largely unknown. In the present study, measured by electrospray ionization linear ion trap mass spectrometry, C18-ceramide was significantly lower in glioma tumor tissues compared with controls (P < 0.001), indicating that C18-ceramide might have a role in glioma. These roles were examined by reconstitution of C18-ceramide in U251 and A172 glioma cells via addition of exogenous C18-ceramide or overexpression of CERS1, which has been shown to specifically induce the generation of C18-ceramide. Overexpression of CERS1 or adding exogenous C18-ceramide inhibited cell viability and induced cell death by activating endoplasmic reticulum stress, which induced lethal autophagy and inhibited PI3K/AKT signal pathway in U251 and A172 glioma cells. Moreover, overexpression of CERS1 or adding exogenous C18-ceramide increased the sensitivity of U251 and A172 glioma cells to teniposide (VM-26). Thus, the combined therapy of CERS1/C18-ceramide and VM-26 may be a novel therapeutic strategy for the treatment of human glioma. Impact Journals LLC 2017-10-23 /pmc/articles/PMC5732784/ /pubmed/29262618 http://dx.doi.org/10.18632/oncotarget.21955 Text en Copyright: © 2017 Wang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Wang, Zheng Wen, Lijun Zhu, Fei Wang, Yanping Xie, Qing Chen, Zijun Li, Yunsen Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma |
title | Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma |
title_full | Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma |
title_fullStr | Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma |
title_full_unstemmed | Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma |
title_short | Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma |
title_sort | overexpression of ceramide synthase 1 increases c18-ceramide and leads to lethal autophagy in human glioma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732784/ https://www.ncbi.nlm.nih.gov/pubmed/29262618 http://dx.doi.org/10.18632/oncotarget.21955 |
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