Pinto, Ana Teresa 
ORCID: 0000-0003-0974-2206, Machado, Ana Beatriz ORCID: 0000-0002-7559-7599, Osório, Hugo ORCID: 0000-0002-6362-8255, Pinto, Marta Laranjeiro, Vitorino, Rui ORCID: 0000-0003-3636-5805, Justino, Gonçalo ORCID: 0000-0003-4828-4738, Santa, Cátia, Castro, Flávia ORCID: 0000-0002-2273-2806, Cruz, Tânia, Rodrigues, Carla et al (show 13 more authors)
(2022)
Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression.
Cancers, 15 (1).
270-.
Abstract
<h4>Purpose</h4>To identify a molecular signature of macrophages exposed to clinically relevant ionizing radiation (IR) doses, mirroring radiotherapy sessions.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Irradiated macrophages present lower ATP levels and glucose uptake, and exhibit decreased cathepsin D expression, while increasing TfR1 expression and altering iron metabolism.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | cathepsin D, ionizing radiation, iron metabolism, macrophages, proteomics, radiotherapy, transferrin receptor 1 (TfR1) |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 20 Jan 2023 10:33 |
| Last Modified: | 02 Feb 2023 23:19 |
| DOI: | 10.3390/cancers15010270 |
| Open Access URL: | https://www.mdpi.com/2072-6694/15/1/270 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3167188 |
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