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The passage from bone marrow niche to bloodstream triggers the metabolic impairment in Fanconi Anemia mononuclear cells
Fanconi Anemia (FA) is a disease characterized by bone marrow (BM) failure and aplastic anemia. In addition to a defective DNA repair system, other mechanisms are involved in its pathogenesis, such as defective mitochondrial metabolism, accumulation of lipids, and increment of oxidative stress produ...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327247/ https://www.ncbi.nlm.nih.gov/pubmed/32863220 http://dx.doi.org/10.1016/j.redox.2020.101618 |
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author | Cappelli, Enrico Degan, Paolo Bruno, Silvia Pierri, Filomena Miano, Maurizio Raggi, Federica Farruggia, Piero Mecucci, Cristina Crescenzi, Barbara Naim, Valeria Dufour, Carlo Ravera, Silvia |
author_facet | Cappelli, Enrico Degan, Paolo Bruno, Silvia Pierri, Filomena Miano, Maurizio Raggi, Federica Farruggia, Piero Mecucci, Cristina Crescenzi, Barbara Naim, Valeria Dufour, Carlo Ravera, Silvia |
author_sort | Cappelli, Enrico |
collection | PubMed |
description | Fanconi Anemia (FA) is a disease characterized by bone marrow (BM) failure and aplastic anemia. In addition to a defective DNA repair system, other mechanisms are involved in its pathogenesis, such as defective mitochondrial metabolism, accumulation of lipids, and increment of oxidative stress production. To better understand the role of these metabolic alterations in the process of HSC maturation in FA, we evaluated several biochemical and cellular parameters on mononuclear cells isolated from the bone marrow of FA patients or healthy donors. To mimic the cellular residence in the BM niche or their exit from the BM niche to the bloodstream, cells have been grown in hypoxic or normoxic conditions, respectively. The data show that, in normoxic conditions, a switch from anaerobic to aerobic metabolism occurs both in healthy and in pathological samples. However, in FA cells this change is associated with altered oxidative phosphorylation, the increment of oxidative stress production, no activation of the endogenous antioxidant defenses and arrest in the G2M phase of the cell cycle. By contrast, FA cells grown in hypoxic conditions do not show cell cycle and metabolic alterations in comparison to the healthy control, maintaining both an anaerobic flux. The data reported herein suggests that the passage from the BM niche to the bloodstream represents a crucial point in the FA pathogenesis associated with mitochondrial dysfunction. |
format | Online Article Text |
id | pubmed-7327247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-73272472020-07-06 The passage from bone marrow niche to bloodstream triggers the metabolic impairment in Fanconi Anemia mononuclear cells Cappelli, Enrico Degan, Paolo Bruno, Silvia Pierri, Filomena Miano, Maurizio Raggi, Federica Farruggia, Piero Mecucci, Cristina Crescenzi, Barbara Naim, Valeria Dufour, Carlo Ravera, Silvia Redox Biol Research Paper Fanconi Anemia (FA) is a disease characterized by bone marrow (BM) failure and aplastic anemia. In addition to a defective DNA repair system, other mechanisms are involved in its pathogenesis, such as defective mitochondrial metabolism, accumulation of lipids, and increment of oxidative stress production. To better understand the role of these metabolic alterations in the process of HSC maturation in FA, we evaluated several biochemical and cellular parameters on mononuclear cells isolated from the bone marrow of FA patients or healthy donors. To mimic the cellular residence in the BM niche or their exit from the BM niche to the bloodstream, cells have been grown in hypoxic or normoxic conditions, respectively. The data show that, in normoxic conditions, a switch from anaerobic to aerobic metabolism occurs both in healthy and in pathological samples. However, in FA cells this change is associated with altered oxidative phosphorylation, the increment of oxidative stress production, no activation of the endogenous antioxidant defenses and arrest in the G2M phase of the cell cycle. By contrast, FA cells grown in hypoxic conditions do not show cell cycle and metabolic alterations in comparison to the healthy control, maintaining both an anaerobic flux. The data reported herein suggests that the passage from the BM niche to the bloodstream represents a crucial point in the FA pathogenesis associated with mitochondrial dysfunction. Elsevier 2020-06-23 /pmc/articles/PMC7327247/ /pubmed/32863220 http://dx.doi.org/10.1016/j.redox.2020.101618 Text en © 2020 Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Cappelli, Enrico Degan, Paolo Bruno, Silvia Pierri, Filomena Miano, Maurizio Raggi, Federica Farruggia, Piero Mecucci, Cristina Crescenzi, Barbara Naim, Valeria Dufour, Carlo Ravera, Silvia The passage from bone marrow niche to bloodstream triggers the metabolic impairment in Fanconi Anemia mononuclear cells |
title | The passage from bone marrow niche to bloodstream triggers the metabolic impairment in Fanconi Anemia mononuclear cells |
title_full | The passage from bone marrow niche to bloodstream triggers the metabolic impairment in Fanconi Anemia mononuclear cells |
title_fullStr | The passage from bone marrow niche to bloodstream triggers the metabolic impairment in Fanconi Anemia mononuclear cells |
title_full_unstemmed | The passage from bone marrow niche to bloodstream triggers the metabolic impairment in Fanconi Anemia mononuclear cells |
title_short | The passage from bone marrow niche to bloodstream triggers the metabolic impairment in Fanconi Anemia mononuclear cells |
title_sort | passage from bone marrow niche to bloodstream triggers the metabolic impairment in fanconi anemia mononuclear cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327247/ https://www.ncbi.nlm.nih.gov/pubmed/32863220 http://dx.doi.org/10.1016/j.redox.2020.101618 |
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