Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/150803 |
Resumo: | LA/P/0056/2020 and POCI-01-0145-FEDER-31859/2017), the Program “COMPETE Programa Operacional Factores de Competitividade” (FCOMP-01-0124-FEDER-010915) QREN, the European Union (FEDER—Fundo Europeu de Desenvolvimento Regional), Proteostasis COST Action (BM1307), by The National Mass Spectrometry Network (POCI-01-0145-FEDER-402-022125 Ref. ROTEIRO/0028/2013), and the Prize L’Óreal for Women in Science (Foundation L’Óreal/FCT/UNESCO). This work was also funded (in part) by Programa Operacional Regional do Norte and co-funded by European Regional Development Fund under the project “The Porto Comprehensive Cancer Center” with the reference NORTE-01-0145-FEDER-072678–Consórcio PORTO.CCC–Porto Comprehensive Cancer Center Raquel Seruca. Authors also would like to acknowledge also IPATIMUP for the financial support provided through the project: CANCER_CHALLENGE2022, and to International Iberian Nanotechnology Laboratory (INL), and FCT2012-Investigator Program (for MJ Oliveira), EMBO and EACR travel Fellowships, Cancer Research UK (C99667/A12918) and Welcome Trust (097945/B/11/Z) for their grant support. Publisher Copyright: © 2022 by the authors. |
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Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expressioncathepsin Dionizing radiationiron metabolismmacrophagesproteomicsradiotherapytransferrin receptor 1 (TfR1)OncologyCancer ResearchSDG 3 - Good Health and Well-beingLA/P/0056/2020 and POCI-01-0145-FEDER-31859/2017), the Program “COMPETE Programa Operacional Factores de Competitividade” (FCOMP-01-0124-FEDER-010915) QREN, the European Union (FEDER—Fundo Europeu de Desenvolvimento Regional), Proteostasis COST Action (BM1307), by The National Mass Spectrometry Network (POCI-01-0145-FEDER-402-022125 Ref. ROTEIRO/0028/2013), and the Prize L’Óreal for Women in Science (Foundation L’Óreal/FCT/UNESCO). This work was also funded (in part) by Programa Operacional Regional do Norte and co-funded by European Regional Development Fund under the project “The Porto Comprehensive Cancer Center” with the reference NORTE-01-0145-FEDER-072678–Consórcio PORTO.CCC–Porto Comprehensive Cancer Center Raquel Seruca. Authors also would like to acknowledge also IPATIMUP for the financial support provided through the project: CANCER_CHALLENGE2022, and to International Iberian Nanotechnology Laboratory (INL), and FCT2012-Investigator Program (for MJ Oliveira), EMBO and EACR travel Fellowships, Cancer Research UK (C99667/A12918) and Welcome Trust (097945/B/11/Z) for their grant support. Publisher Copyright: © 2022 by the authors.Purpose: To identify a molecular signature of macrophages exposed to clinically relevant ionizing radiation (IR) doses, mirroring radiotherapy sessions. Methods: Human monocyte-derived macrophages were exposed to 2 Gy/ fraction/ day for 5 days, mimicking one week of cancer patient’s radiotherapy. Protein expression profile by proteomics was performed. Results: A gene ontology analysis revealed that radiation-induced protein changes are associated with metabolic alterations, which were further supported by a reduction of both cellular ATP levels and glucose uptake. Most of the radiation-induced deregulated targets exhibited a decreased expression, as was the case of cathepsin D, a lysosomal protease associated with cell death, which was validated by Western blot. We also found that irradiated macrophages exhibited an increased expression of the transferrin receptor 1 (TfR1), which is responsible for the uptake of transferrin-bound iron. TfR1 upregulation was also found in tumor-associated mouse macrophages upon tumor irradiation. In vitro irradiated macrophages also presented a trend for increased divalent metal transporter 1 (DMT1), which transports iron from the endosome to the cytosol, and a significant increase in iron release. Conclusions: Irradiated macrophages present lower ATP levels and glucose uptake, and exhibit decreased cathepsin D expression, while increasing TfR1 expression and altering iron metabolism.DQ - Departamento de QuímicaLAQV@REQUIMTERUNPinto, Ana TeresaMachado, Ana BeatrizOsório, HugoPinto, Marta LaranjeiroVitorino, RuiJustino, GonçaloSanta, CátiaCastro, FláviaCruz, TâniaRodrigues, CarlaLima, JorgeSousa, José Luís R.Cardoso, Ana PatríciaFigueira, RitaMonteiro, ArmandaMarques, MargaridaManadas, BrunoPauwels, JarneGevaert, KrisMareel, MarcRocha, SóniaDuarte, TiagoOliveira, Maria José2023-03-17T22:31:41Z2022-12-302022-12-30T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article21application/pdfhttp://hdl.handle.net/10362/150803engPinto, A. T., Machado, A. B., Osório, H., Pinto, M. L., Vitorino, R., Justino, G., Santa, C., Castro, F., Cruz, T., Rodrigues, C., Lima, J., Sousa, J. L. R., Cardoso, A. P., Figueira, R., Monteiro, A., Marques, M., Manadas, B., Pauwels, J., Gevaert, K., ... Oliveira, M. J. (2022). Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression. Cancers, 15(1), [270]. https://doi.org/10.3390/cancers150102702072-6694PURE: 56243076https://doi.org/10.3390/cancers15010270info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-10T16:12:58ZPortal AgregadorONG |
| dc.title.none.fl_str_mv |
Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression |
| title |
Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression |
| spellingShingle |
Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression Pinto, Ana Teresa cathepsin D ionizing radiation iron metabolism macrophages proteomics radiotherapy transferrin receptor 1 (TfR1) Oncology Cancer Research SDG 3 - Good Health and Well-being |
| title_short |
Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression |
| title_full |
Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression |
| title_fullStr |
Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression |
| title_full_unstemmed |
Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression |
| title_sort |
Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression |
| author |
Pinto, Ana Teresa |
| author_facet |
Pinto, Ana Teresa Machado, Ana Beatriz Osório, Hugo Pinto, Marta Laranjeiro Vitorino, Rui Justino, Gonçalo Santa, Cátia Castro, Flávia Cruz, Tânia Rodrigues, Carla Lima, Jorge Sousa, José Luís R. Cardoso, Ana Patrícia Figueira, Rita Monteiro, Armanda Marques, Margarida Manadas, Bruno Pauwels, Jarne Gevaert, Kris Mareel, Marc Rocha, Sónia Duarte, Tiago Oliveira, Maria José |
| author_role |
author |
| author2 |
Machado, Ana Beatriz Osório, Hugo Pinto, Marta Laranjeiro Vitorino, Rui Justino, Gonçalo Santa, Cátia Castro, Flávia Cruz, Tânia Rodrigues, Carla Lima, Jorge Sousa, José Luís R. Cardoso, Ana Patrícia Figueira, Rita Monteiro, Armanda Marques, Margarida Manadas, Bruno Pauwels, Jarne Gevaert, Kris Mareel, Marc Rocha, Sónia Duarte, Tiago Oliveira, Maria José |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
DQ - Departamento de Química LAQV@REQUIMTE RUN |
| dc.contributor.author.fl_str_mv |
Pinto, Ana Teresa Machado, Ana Beatriz Osório, Hugo Pinto, Marta Laranjeiro Vitorino, Rui Justino, Gonçalo Santa, Cátia Castro, Flávia Cruz, Tânia Rodrigues, Carla Lima, Jorge Sousa, José Luís R. Cardoso, Ana Patrícia Figueira, Rita Monteiro, Armanda Marques, Margarida Manadas, Bruno Pauwels, Jarne Gevaert, Kris Mareel, Marc Rocha, Sónia Duarte, Tiago Oliveira, Maria José |
| dc.subject.por.fl_str_mv |
cathepsin D ionizing radiation iron metabolism macrophages proteomics radiotherapy transferrin receptor 1 (TfR1) Oncology Cancer Research SDG 3 - Good Health and Well-being |
| topic |
cathepsin D ionizing radiation iron metabolism macrophages proteomics radiotherapy transferrin receptor 1 (TfR1) Oncology Cancer Research SDG 3 - Good Health and Well-being |
| description |
LA/P/0056/2020 and POCI-01-0145-FEDER-31859/2017), the Program “COMPETE Programa Operacional Factores de Competitividade” (FCOMP-01-0124-FEDER-010915) QREN, the European Union (FEDER—Fundo Europeu de Desenvolvimento Regional), Proteostasis COST Action (BM1307), by The National Mass Spectrometry Network (POCI-01-0145-FEDER-402-022125 Ref. ROTEIRO/0028/2013), and the Prize L’Óreal for Women in Science (Foundation L’Óreal/FCT/UNESCO). This work was also funded (in part) by Programa Operacional Regional do Norte and co-funded by European Regional Development Fund under the project “The Porto Comprehensive Cancer Center” with the reference NORTE-01-0145-FEDER-072678–Consórcio PORTO.CCC–Porto Comprehensive Cancer Center Raquel Seruca. Authors also would like to acknowledge also IPATIMUP for the financial support provided through the project: CANCER_CHALLENGE2022, and to International Iberian Nanotechnology Laboratory (INL), and FCT2012-Investigator Program (for MJ Oliveira), EMBO and EACR travel Fellowships, Cancer Research UK (C99667/A12918) and Welcome Trust (097945/B/11/Z) for their grant support. Publisher Copyright: © 2022 by the authors. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-12-30 2022-12-30T00:00:00Z 2023-03-17T22:31:41Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10362/150803 |
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http://hdl.handle.net/10362/150803 |
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eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Pinto, A. T., Machado, A. B., Osório, H., Pinto, M. L., Vitorino, R., Justino, G., Santa, C., Castro, F., Cruz, T., Rodrigues, C., Lima, J., Sousa, J. L. R., Cardoso, A. P., Figueira, R., Monteiro, A., Marques, M., Manadas, B., Pauwels, J., Gevaert, K., ... Oliveira, M. J. (2022). Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression. Cancers, 15(1), [270]. https://doi.org/10.3390/cancers15010270 2072-6694 PURE: 56243076 https://doi.org/10.3390/cancers15010270 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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21 application/pdf |
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