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Macrophage resistance to ionizing radiation exposure is accompanied by decreased cathepsin D and increased transferrin receptor 1 expression

Ana Teresa Pinto, Ana Beatriz Machado, Hugo Osório, Marta Laranjeiro Pinto, Rui Vitorino, Gonçalo Justino, Cátia Santa, Flávia Castro, Tânia Cruz, Carla Rodrigues, et al.
(2023) CANCERS. 15(1).
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Abstract
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.
Keywords
Cancer Research, Oncology, iron metabolism, transferrin receptor 1 (TfR1), cathepsin D, proteomics, radiotherapy, ionizing radiation, macrophages

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MLA
Pinto, Ana Teresa, et al. “Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression.” CANCERS, vol. 15, no. 1, MDPI AG, 2023, doi:10.3390/cancers15010270.
APA
Pinto, A. T., Machado, A. B., Osório, H., Pinto, M. L., Vitorino, R., Justino, G., … Oliveira, M. J. (2023). Macrophage resistance to ionizing radiation exposure is accompanied by decreased cathepsin D and increased transferrin receptor 1 expression. CANCERS, 15(1). https://doi.org/10.3390/cancers15010270
Chicago author-date
Pinto, Ana Teresa, Ana Beatriz Machado, Hugo Osório, Marta Laranjeiro Pinto, Rui Vitorino, Gonçalo Justino, Cátia Santa, et al. 2023. “Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression.” CANCERS 15 (1). https://doi.org/10.3390/cancers15010270.
Chicago author-date (all authors)
Pinto, Ana Teresa, Ana Beatriz Machado, Hugo Osório, Marta Laranjeiro Pinto, Rui Vitorino, Gonçalo Justino, Cátia Santa, Flávia Castro, Tânia Cruz, Carla Rodrigues, Jorge Lima, José Luís R. Sousa, Ana Patrícia Cardoso, Rita Figueira, Armanda Monteiro, Margarida Marques, Bruno Manadas, Jarne Pauwels, Kris Gevaert, Marc Mareel, Sónia Rocha, Tiago Duarte, and Maria José Oliveira. 2023. “Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression.” CANCERS 15 (1). doi:10.3390/cancers15010270.
Vancouver
1.
Pinto AT, Machado AB, Osório H, Pinto ML, Vitorino R, Justino G, et al. Macrophage resistance to ionizing radiation exposure is accompanied by decreased cathepsin D and increased transferrin receptor 1 expression. CANCERS. 2023;15(1).
IEEE
[1]
A. T. Pinto et al., “Macrophage resistance to ionizing radiation exposure is accompanied by decreased cathepsin D and increased transferrin receptor 1 expression,” CANCERS, vol. 15, no. 1, 2023.
@article{01GPB1JJC1C790GV7CGY5M9954,
  abstract     = {{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.}},
  articleno    = {{270}},
  author       = {{Pinto, Ana Teresa and Machado, Ana Beatriz and Osório, Hugo and Pinto, Marta Laranjeiro and Vitorino, Rui and Justino, Gonçalo and Santa, Cátia and Castro, Flávia and Cruz, Tânia and Rodrigues, Carla and Lima, Jorge and Sousa, José Luís R. and Cardoso, Ana Patrícia and Figueira, Rita and Monteiro, Armanda and Marques, Margarida and Manadas, Bruno and Pauwels, Jarne and Gevaert, Kris and Mareel, Marc and Rocha, Sónia and Duarte, Tiago and Oliveira, Maria José}},
  issn         = {{2072-6694}},
  journal      = {{CANCERS}},
  keywords     = {{Cancer Research,Oncology,iron metabolism,transferrin receptor 1 (TfR1),cathepsin D,proteomics,radiotherapy,ionizing radiation,macrophages}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{21}},
  publisher    = {{MDPI AG}},
  title        = {{Macrophage resistance to ionizing radiation exposure is accompanied by decreased cathepsin D and increased transferrin receptor 1 expression}},
  url          = {{http://doi.org/10.3390/cancers15010270}},
  volume       = {{15}},
  year         = {{2023}},
}
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