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Glutamine synthetase expression rescues human dendritic cell survival in a glutamine-deprived environment
INTRODUCTION: Glutamine deficiency is a well-known feature of the tumor environment. Here we analyzed the impact of glutamine deprivation on human myeloid cell survival and function. METHODS: Different types of myeloid cells were cultured in the absence or presence of glutamine and/or with L-methion...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9894315/ https://www.ncbi.nlm.nih.gov/pubmed/36741028 http://dx.doi.org/10.3389/fonc.2023.1120194 |
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author | Schoeppe, Robert Babl, Nathalie Decking, Sonja-Maria Schönhammer, Gabriele Siegmund, Andreas Bruss, Christina Dettmer, Katja Oefner, Peter J. Frick, Linus Weigert, Anna Jantsch, Jonathan Herr, Wolfgang Rehli, Michael Renner, Kathrin Kreutz, Marina |
author_facet | Schoeppe, Robert Babl, Nathalie Decking, Sonja-Maria Schönhammer, Gabriele Siegmund, Andreas Bruss, Christina Dettmer, Katja Oefner, Peter J. Frick, Linus Weigert, Anna Jantsch, Jonathan Herr, Wolfgang Rehli, Michael Renner, Kathrin Kreutz, Marina |
author_sort | Schoeppe, Robert |
collection | PubMed |
description | INTRODUCTION: Glutamine deficiency is a well-known feature of the tumor environment. Here we analyzed the impact of glutamine deprivation on human myeloid cell survival and function. METHODS: Different types of myeloid cells were cultured in the absence or presence of glutamine and/or with L-methionine-S-sulfoximine (MSO), an irreversible glutamine synthetase (GS) inhibitor. GS expression was analyzed on mRNA and protein level. GS activity and the conversion of glutamate to glutamine by myeloid cells was followed by 13C tracing analyses. RESULTS: The absence of extracellular glutamine only slightly affected postmitotic human monocyte to dendritic cell (DC) differentiation, function and survival. Similar results were obtained for monocyte-derived macrophages. In contrast, proliferation of the monocytic leukemia cell line THP-1 was significantly suppressed. While macrophages exhibited high constitutive GS expression, glutamine deprivation induced GS in DC and THP-1. Accordingly, proliferation of THP-1 was rescued by addition of the GS substrate glutamate and 13C tracing analyses revealed conversion of glutamate to glutamine. Supplementation with the GS inhibitor MSO reduced the survival of DC and macrophages and counteracted the proliferation rescue of THP-1 by glutamate. DISCUSSION: Our results show that GS supports myeloid cell survival in a glutamine poor environment. Notably, in addition to suppressing proliferation and survival of tumor cells, the blockade of GS also targets immune cells such as DCs and macrophages. |
format | Online Article Text |
id | pubmed-9894315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98943152023-02-03 Glutamine synthetase expression rescues human dendritic cell survival in a glutamine-deprived environment Schoeppe, Robert Babl, Nathalie Decking, Sonja-Maria Schönhammer, Gabriele Siegmund, Andreas Bruss, Christina Dettmer, Katja Oefner, Peter J. Frick, Linus Weigert, Anna Jantsch, Jonathan Herr, Wolfgang Rehli, Michael Renner, Kathrin Kreutz, Marina Front Oncol Oncology INTRODUCTION: Glutamine deficiency is a well-known feature of the tumor environment. Here we analyzed the impact of glutamine deprivation on human myeloid cell survival and function. METHODS: Different types of myeloid cells were cultured in the absence or presence of glutamine and/or with L-methionine-S-sulfoximine (MSO), an irreversible glutamine synthetase (GS) inhibitor. GS expression was analyzed on mRNA and protein level. GS activity and the conversion of glutamate to glutamine by myeloid cells was followed by 13C tracing analyses. RESULTS: The absence of extracellular glutamine only slightly affected postmitotic human monocyte to dendritic cell (DC) differentiation, function and survival. Similar results were obtained for monocyte-derived macrophages. In contrast, proliferation of the monocytic leukemia cell line THP-1 was significantly suppressed. While macrophages exhibited high constitutive GS expression, glutamine deprivation induced GS in DC and THP-1. Accordingly, proliferation of THP-1 was rescued by addition of the GS substrate glutamate and 13C tracing analyses revealed conversion of glutamate to glutamine. Supplementation with the GS inhibitor MSO reduced the survival of DC and macrophages and counteracted the proliferation rescue of THP-1 by glutamate. DISCUSSION: Our results show that GS supports myeloid cell survival in a glutamine poor environment. Notably, in addition to suppressing proliferation and survival of tumor cells, the blockade of GS also targets immune cells such as DCs and macrophages. Frontiers Media S.A. 2023-01-19 /pmc/articles/PMC9894315/ /pubmed/36741028 http://dx.doi.org/10.3389/fonc.2023.1120194 Text en Copyright © 2023 Schoeppe, Babl, Decking, Schönhammer, Siegmund, Bruss, Dettmer, Oefner, Frick, Weigert, Jantsch, Herr, Rehli, Renner and Kreutz https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Schoeppe, Robert Babl, Nathalie Decking, Sonja-Maria Schönhammer, Gabriele Siegmund, Andreas Bruss, Christina Dettmer, Katja Oefner, Peter J. Frick, Linus Weigert, Anna Jantsch, Jonathan Herr, Wolfgang Rehli, Michael Renner, Kathrin Kreutz, Marina Glutamine synthetase expression rescues human dendritic cell survival in a glutamine-deprived environment |
title | Glutamine synthetase expression rescues human dendritic cell survival in a glutamine-deprived environment |
title_full | Glutamine synthetase expression rescues human dendritic cell survival in a glutamine-deprived environment |
title_fullStr | Glutamine synthetase expression rescues human dendritic cell survival in a glutamine-deprived environment |
title_full_unstemmed | Glutamine synthetase expression rescues human dendritic cell survival in a glutamine-deprived environment |
title_short | Glutamine synthetase expression rescues human dendritic cell survival in a glutamine-deprived environment |
title_sort | glutamine synthetase expression rescues human dendritic cell survival in a glutamine-deprived environment |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9894315/ https://www.ncbi.nlm.nih.gov/pubmed/36741028 http://dx.doi.org/10.3389/fonc.2023.1120194 |
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