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Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function
Xanthine oxidase (XOD) is an enzyme which plays a central role in purine catabolism by converting hypoxanthine into xanthine and then further into uric acid. Here we report that XOD is activated in THP-1 human myeloid cells in response to pro-inflammatory and growth factor stimulation. This effect o...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158321/ https://www.ncbi.nlm.nih.gov/pubmed/25200751 http://dx.doi.org/10.1038/srep06307 |
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author | Abooali, Maryam Lall, Gurprit S. Coughlan, Karen Lall, Harjinder S. Gibbs, Bernhard F. Sumbayev, Vadim V. |
author_facet | Abooali, Maryam Lall, Gurprit S. Coughlan, Karen Lall, Harjinder S. Gibbs, Bernhard F. Sumbayev, Vadim V. |
author_sort | Abooali, Maryam |
collection | PubMed |
description | Xanthine oxidase (XOD) is an enzyme which plays a central role in purine catabolism by converting hypoxanthine into xanthine and then further into uric acid. Here we report that XOD is activated in THP-1 human myeloid cells in response to pro-inflammatory and growth factor stimulation. This effect occurred following stimulation of THP-1 cells with ligands of plasma membrane associated TLRs 2 and 4, endosomal TLRs 7 and 8 as well as stem cell growth factor (SCF). Hypoxia-inducible factor 1 (HIF-1) and activator protein 1 (AP-1) transcription complexes were found to be responsible for XOD upregulation. Importantly, the mammalian target of rapamycin (mTOR), a major myeloid cell translation regulator, was also found to be essential for XOD activation. Specific inhibition of XOD by allopurinol and sodium tungstate led to an increase in intracellular AMP levels triggering downregulation of mTOR activation by phosphorylation of its T2446 residue. Taken together, our results demonstrate for the first time that XOD is not only activated by pro-inflammatory stimuli or SCF but also plays an important role in maintaining mTOR-dependent translational control during the biological responses of human myeloid cells. |
format | Online Article Text |
id | pubmed-4158321 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-41583212014-09-10 Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function Abooali, Maryam Lall, Gurprit S. Coughlan, Karen Lall, Harjinder S. Gibbs, Bernhard F. Sumbayev, Vadim V. Sci Rep Article Xanthine oxidase (XOD) is an enzyme which plays a central role in purine catabolism by converting hypoxanthine into xanthine and then further into uric acid. Here we report that XOD is activated in THP-1 human myeloid cells in response to pro-inflammatory and growth factor stimulation. This effect occurred following stimulation of THP-1 cells with ligands of plasma membrane associated TLRs 2 and 4, endosomal TLRs 7 and 8 as well as stem cell growth factor (SCF). Hypoxia-inducible factor 1 (HIF-1) and activator protein 1 (AP-1) transcription complexes were found to be responsible for XOD upregulation. Importantly, the mammalian target of rapamycin (mTOR), a major myeloid cell translation regulator, was also found to be essential for XOD activation. Specific inhibition of XOD by allopurinol and sodium tungstate led to an increase in intracellular AMP levels triggering downregulation of mTOR activation by phosphorylation of its T2446 residue. Taken together, our results demonstrate for the first time that XOD is not only activated by pro-inflammatory stimuli or SCF but also plays an important role in maintaining mTOR-dependent translational control during the biological responses of human myeloid cells. Nature Publishing Group 2014-09-09 /pmc/articles/PMC4158321/ /pubmed/25200751 http://dx.doi.org/10.1038/srep06307 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 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 in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Article Abooali, Maryam Lall, Gurprit S. Coughlan, Karen Lall, Harjinder S. Gibbs, Bernhard F. Sumbayev, Vadim V. Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function |
title | Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function |
title_full | Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function |
title_fullStr | Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function |
title_full_unstemmed | Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function |
title_short | Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function |
title_sort | crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158321/ https://www.ncbi.nlm.nih.gov/pubmed/25200751 http://dx.doi.org/10.1038/srep06307 |
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