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Stereospecific induction of apoptosis in tumor cells via endogenous C(16)-ceramide and distinct transcripts
Concentration and distribution of individual endogenous ceramide species is crucial for apoptosis induction in response to various stimuli. Exogenous ceramide analogs induce apoptosis and can in turn modify the composition/concentrations of endogenous ceramide species and associated signaling. In th...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979478/ https://www.ncbi.nlm.nih.gov/pubmed/27551447 http://dx.doi.org/10.1038/cddiscovery.2015.13 |
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author | Blaess, M Le, HP Claus, RA Kohl, M Deigner, H-P |
author_facet | Blaess, M Le, HP Claus, RA Kohl, M Deigner, H-P |
author_sort | Blaess, M |
collection | PubMed |
description | Concentration and distribution of individual endogenous ceramide species is crucial for apoptosis induction in response to various stimuli. Exogenous ceramide analogs induce apoptosis and can in turn modify the composition/concentrations of endogenous ceramide species and associated signaling. In this study, we show here that the elevation of endogenous C(16)-ceramide levels is a common feature of several known apoptosis-inducing triggers like mmLDL, TNF-alpha, H(2)O(2) and exogenous C(6)-ceramide. Vice versa apoptosis requires elevation of endogenous C(16)-ceramide levels in cells. Enantiomers of a synthetic ceramide analog HPL-1RS36N have been developed as probes and vary in their capacity to inducing apoptosis in macrophages and HT-29 cells. Apoptosis induction by the two synthetic ceramide analogs HPL-39N and HPL-1R36N correlates with generation of cellular C(16)-ceramide concentration. In contrast to the S-enantiomer HPL-1S36N, the R-enantiomer HPL-1R36N shows significant effects on the expression of distinct genes known to be involved in cell cycle, cell growth and cell death (CXCL10, CCL5 and TNF-alpha), similarly on apoptosis induction. Enantioselective effects on transcription induced by metabolically stable synthetic probes provide clues on molecular mechanisms of ceramide-induced signaling, as well as leads for future anti-cancer agents. |
format | Online Article Text |
id | pubmed-4979478 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49794782016-08-22 Stereospecific induction of apoptosis in tumor cells via endogenous C(16)-ceramide and distinct transcripts Blaess, M Le, HP Claus, RA Kohl, M Deigner, H-P Cell Death Discov Article Concentration and distribution of individual endogenous ceramide species is crucial for apoptosis induction in response to various stimuli. Exogenous ceramide analogs induce apoptosis and can in turn modify the composition/concentrations of endogenous ceramide species and associated signaling. In this study, we show here that the elevation of endogenous C(16)-ceramide levels is a common feature of several known apoptosis-inducing triggers like mmLDL, TNF-alpha, H(2)O(2) and exogenous C(6)-ceramide. Vice versa apoptosis requires elevation of endogenous C(16)-ceramide levels in cells. Enantiomers of a synthetic ceramide analog HPL-1RS36N have been developed as probes and vary in their capacity to inducing apoptosis in macrophages and HT-29 cells. Apoptosis induction by the two synthetic ceramide analogs HPL-39N and HPL-1R36N correlates with generation of cellular C(16)-ceramide concentration. In contrast to the S-enantiomer HPL-1S36N, the R-enantiomer HPL-1R36N shows significant effects on the expression of distinct genes known to be involved in cell cycle, cell growth and cell death (CXCL10, CCL5 and TNF-alpha), similarly on apoptosis induction. Enantioselective effects on transcription induced by metabolically stable synthetic probes provide clues on molecular mechanisms of ceramide-induced signaling, as well as leads for future anti-cancer agents. Nature Publishing Group 2015-07-27 /pmc/articles/PMC4979478/ /pubmed/27551447 http://dx.doi.org/10.1038/cddiscovery.2015.13 Text en Copyright © 2015 Cell Death Differentiation Association http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Blaess, M Le, HP Claus, RA Kohl, M Deigner, H-P Stereospecific induction of apoptosis in tumor cells via endogenous C(16)-ceramide and distinct transcripts |
title | Stereospecific induction of apoptosis in tumor cells via endogenous C(16)-ceramide and distinct transcripts |
title_full | Stereospecific induction of apoptosis in tumor cells via endogenous C(16)-ceramide and distinct transcripts |
title_fullStr | Stereospecific induction of apoptosis in tumor cells via endogenous C(16)-ceramide and distinct transcripts |
title_full_unstemmed | Stereospecific induction of apoptosis in tumor cells via endogenous C(16)-ceramide and distinct transcripts |
title_short | Stereospecific induction of apoptosis in tumor cells via endogenous C(16)-ceramide and distinct transcripts |
title_sort | stereospecific induction of apoptosis in tumor cells via endogenous c(16)-ceramide and distinct transcripts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979478/ https://www.ncbi.nlm.nih.gov/pubmed/27551447 http://dx.doi.org/10.1038/cddiscovery.2015.13 |
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