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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...

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Autores principales: Wang, Zheng, Wen, Lijun, Zhu, Fei, Wang, Yanping, Xie, Qing, Chen, Zijun, Li, Yunsen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
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.
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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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