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Trust","award":["SFRH\/BD\/74144\/2010"],"award-info":[{"award-number":["SFRH\/BD\/74144\/2010"]}]},{"name":"Welcome Trust","award":["SFRH\/BD\/81103\/2011"],"award-info":[{"award-number":["SFRH\/BD\/81103\/2011"]}]},{"name":"Welcome Trust","award":["SFRH\/BD\/88419\/2012"],"award-info":[{"award-number":["SFRH\/BD\/88419\/2012"]}]},{"name":"Welcome Trust","award":["C99667\/A12918"],"award-info":[{"award-number":["C99667\/A12918"]}]},{"name":"Welcome Trust","award":["097945\/B\/11\/Z"],"award-info":[{"award-number":["097945\/B\/11\/Z"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/cancers15010270","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T03:00:59Z","timestamp":1672628459000},"page":"270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0974-2206","authenticated-orcid":false,"given":"Ana Teresa","family":"Pinto","sequence":"first","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB\u2013Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Department of Medical Sciences, Institute of Biomedicine (iBiMED), Universidade de Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7559-7599","authenticated-orcid":false,"given":"Ana Beatriz","family":"Machado","sequence":"additional","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB\u2013Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Champalimaud Centre for the Unknown, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-8255","authenticated-orcid":false,"given":"Hugo","family":"Os\u00f3rio","sequence":"additional","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2013Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Departament of Pathology, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"}]},{"given":"Marta Laranjeiro","family":"Pinto","sequence":"additional","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB\u2013Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3636-5805","authenticated-orcid":false,"given":"Rui","family":"Vitorino","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Institute of Biomedicine (iBiMED), Universidade de Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4828-4738","authenticated-orcid":false,"given":"Gon\u00e7alo","family":"Justino","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural\u2013Institute of Molecular Sciences, Instituto Superior T\u00e9cnico, Universidade T\u00e9cnica de Lisboa, 1049-001 Lisboa, Portugal"}]},{"given":"C\u00e1tia","family":"Santa","sequence":"additional","affiliation":[{"name":"CNC\u2013Center for Neuroscience and Cell Biology, Universidade de Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Institute for Interdisciplinary Research (III), Universidade de Coimbra, 3030-789 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2273-2806","authenticated-orcid":false,"given":"Fl\u00e1via","family":"Castro","sequence":"additional","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB\u2013Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"T\u00e2nia","family":"Cruz","sequence":"additional","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB\u2013Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Carla","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"REQUIMTE\u2013LAQV, Chemistry Department, NOVA School of Science and Technology, Universidade de Lisboa, 2829-516 Caparica, Portugal"}]},{"given":"Jorge","family":"Lima","sequence":"additional","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2013Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Jos\u00e9 Lu\u00eds R.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Personal Health Data Science Group, Sano-Centre for Computational Personalised Medicine, 30-054 Krakow, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1987-0316","authenticated-orcid":false,"given":"Ana Patr\u00edcia","family":"Cardoso","sequence":"additional","affiliation":[{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB\u2013Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Rita","family":"Figueira","sequence":"additional","affiliation":[{"name":"Radiotherapy Service, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o (CHUSJ), EPE, 4200-319 Porto, Portugal"}]},{"given":"Armanda","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Radiotherapy Service, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o (CHUSJ), EPE, 4200-319 Porto, 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