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

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

To identify a molecular signature of macrophages exposed to clinically relevant ionizing radiation (IR) doses, mirroring radiotherapy sessions. Human monocyte-derived macrophages were exposed to 2 Gy/ fraction/ day for 5 days, mimicking one week of cancer patient's radiotherapy. Protein express...

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Bibliographic Details
Published in:Cancers Vol. 15; no. 1; p. 270
Main Authors: 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
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 30-12-2022
MDPI
Subjects:
Cancer
Cathepsin D
Cathepsins
Cell death
Cell receptors
Cytosol
Divalent metal transporter-1
Dosimetry
Endosomes
Gene expression
Glucose
Health aspects
Ionizing radiation
Iron
Macrophages
Mass spectrometry
Metabolism
Monocytes
Protein expression
Proteins
Proteomics
Radiation therapy
Reagents
Scientific imaging
Transferrin
Transferrins
Tumor microenvironment
Portugal
St Louis Missouri
United States > US
iron metabolism
transferrin receptor 1 (TfR1)
macrophages
cathepsin D
proteomics
radiotherapy
ionizing radiation
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Summary:To identify a molecular signature of macrophages exposed to clinically relevant ionizing radiation (IR) doses, mirroring radiotherapy sessions. 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. 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. Irradiated macrophages present lower ATP levels and glucose uptake, and exhibit decreased cathepsin D expression, while increasing TfR1 expression and altering iron metabolism.
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ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15010270