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Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression

2022-12-30Artigo científico Acesso aberto
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dc.contributor.authorPinto, Ana Teresa
dc.contributor.authorMachado, Ana Beatriz
dc.contributor.authorOsório, Hugo
dc.contributor.authorPinto, Marta Laranjeiro
dc.contributor.authorVitorino, Rui
dc.contributor.authorJustino, Gonçalo
dc.contributor.authorSanta, Cátia
dc.contributor.authorCastro, Flávia
dc.contributor.authorCruz, Tânia
dc.contributor.authorRodrigues, Carla
dc.contributor.authorLima, Jorge
dc.contributor.authorSousa, José Luís R.
dc.contributor.authorCardoso, Ana Patrícia
dc.contributor.authorFigueira, Rita
dc.contributor.authorMonteiro, Armanda
dc.contributor.authorMarques, Margarida
dc.contributor.authorManadas, Bruno
dc.contributor.authorPauwels, Jarne
dc.contributor.authorGevaert, Kris
dc.contributor.authorMareel, Marc
dc.contributor.authorRocha, Sónia
dc.contributor.authorDuarte, Tiago
dc.contributor.authorOliveira, Maria José
dc.contributor.institutionDQ - Departamento de Química
dc.contributor.institutionLAQV@REQUIMTE
dc.contributor.pblMDPI - Multidisciplinary Digital Publishing Institute
dc.date.accessioned2023-03-17T22:31:41Z
dc.date.available2023-03-17T22:31:41Z
dc.date.issued2022-12-30
dc.descriptionLA/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.
dc.description.abstractPurpose: 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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent21
dc.format.extent3800793
dc.identifier.doi10.3390/cancers15010270
dc.identifier.issn2072-6694
dc.identifier.otherPURE: 56243076
dc.identifier.otherPURE UUID: 4e31e705-03c4-41ca-bafc-54f295a2d987
dc.identifier.otherScopus: 85145996698
dc.identifier.otherWOS: 000909465000001
dc.identifier.urihttp://hdl.handle.net/10362/150803
dc.identifier.urlhttps://www.scopus.com/pages/publications/85145996698
dc.language.isoeng
dc.peerreviewedyes
dc.relationFunding Information: info:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-ONC%2F112511%2F2009/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIM%2F04293%2F2013/PT
dc.relationInstitute for Research and Innovation in Health Sciences
dc.relationInstitute for Biomedicine - Aveiro
dc.relationMAGICIAM: a MAcrophaGe Immunomodulatory-delivery system to prevent Cancer Invasion And Metastasis
dc.relationCenter for Innovative Biomedicine and Biotechnology
dc.relationCenter for Innovative Biomedicine and Biotechnology
dc.relationCentro de Química Estrutural
dc.relationCentro de Química Estrutural
dc.relationROLE OF TUMOUR MICROENVIRONMENT ON MACROPHAGE POLARIZATION: DISSECTING THE ASSOCIATED MECHANISMS
dc.relationANALYSIS OF THE HIPPOCAMPAL AND CORTEX PROTEOME OF MICE EXPOSED TO PSYCHOTROPIC MEDICATION
dc.relationinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00100%2F2020/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBD%2F81103%2F2011/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBD%2F88419%2F2012/PT
dc.subjectcathepsin D
dc.subjectionizing radiation
dc.subjectiron metabolism
dc.subjectmacrophages
dc.subjectproteomics
dc.subjectradiotherapy
dc.subjecttransferrin receptor 1 (TfR1)
dc.subjectOncology
dc.subjectCancer Research
dc.subjectSDG 3 - Good Health and Well-being
dc.titleMacrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expressionen
dc.typejournal article
degois.publication.issue1
degois.publication.titleCancers
degois.publication.volume15
dspace.entity.typePublication
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oaire.awardTitleInstitute for Research and Innovation in Health Sciences
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oaire.awardTitleCenter for Innovative Biomedicine and Biotechnology
oaire.awardTitleCenter for Innovative Biomedicine and Biotechnology
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oaire.awardTitleROLE OF TUMOUR MICROENVIRONMENT ON MACROPHAGE POLARIZATION: DISSECTING THE ASSOCIATED MECHANISMS
oaire.awardTitleANALYSIS OF THE HIPPOCAMPAL AND CORTEX PROTEOME OF MICE EXPOSED TO PSYCHOTROPIC MEDICATION
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