{"id":14895,"date":"2024-01-15T13:32:31","date_gmt":"2024-01-15T12:32:31","guid":{"rendered":"https:\/\/sano.science\/?post_type=research&#038;p=14895"},"modified":"2024-01-15T13:32:32","modified_gmt":"2024-01-15T12:32:32","slug":"macrophage-resistance-to-ionizing-radiation-exposure-is-accompanied-by-decreased-cathepsin-d-and-increased-transferrin-receptor-1-expression","status":"publish","type":"research","link":"https:\/\/sano.science\/research\/macrophage-resistance-to-ionizing-radiation-exposure-is-accompanied-by-decreased-cathepsin-d-and-increased-transferrin-receptor-1-expression\/","title":{"rendered":"Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression"},"content":{"rendered":"\n<h2 class=\"wp-block-heading eplus-wrapper\">Ana Teresa Pinto, Ana Beatriz Machado, Hugo Os\u00f3rio, Marta Laranjeiro Pinto, Rui Vitorino, Gon\u00e7alo Justino, C\u00e1tia Santa, Fl\u00e1via Castro, T\u00e2nia Cruz, Carla Rodrigues, Jorge Lima, Jos\u00e9 Lu\u00eds R Sousa, Ana Patr\u00edcia Cardoso, Rita Figueira, Armanda Monteiro, Margarida Marques, Bruno Manadas, Jarne Pauwels, Kris Gevaert, Marc Mareel, S\u00f3nia Rocha, Tiago Duarte, Maria Jos\u00e9 Oliveira<\/h2>\n\n\n\n<div style=\"height:50px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n\n\n\n<p class=\" eplus-wrapper\">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.<\/p>\n\n\n\n<div style=\"height:50px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n\n\n\n\t\n    \n        \n\t\t\t<a href=\"https:\/\/www.mdpi.com\/2072-6694\/15\/1\/270\" target=\"_blank\" rel= \"noopener noreferrer nofollow\" class=\"button primary \">\n\n\t\t\t\t<span>\n\t\t\t\t\tREAD HERE\n\t\t\t\t<\/span>\n\n\t\t\t<\/a>\n\n        \n    \n","protected":false},"excerpt":{"rendered":"<p>In: Cancers, 2022.<\/p>\n","protected":false},"featured_media":0,"template":"","research_type":[8],"research_team":[14],"class_list":["post-14895","research","type-research","status-publish","hentry","research_type-publications","research_team-computational-intelligence"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.4 (Yoast SEO v27.4) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression - Centre for Computational Personalized Medicine<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/sano.science\/research\/macrophage-resistance-to-ionizing-radiation-exposure-is-accompanied-by-decreased-cathepsin-d-and-increased-transferrin-receptor-1-expression\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression\" \/>\n<meta property=\"og:description\" content=\"In: Cancers, 2022.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/sano.science\/research\/macrophage-resistance-to-ionizing-radiation-exposure-is-accompanied-by-decreased-cathepsin-d-and-increased-transferrin-receptor-1-expression\/\" \/>\n<meta property=\"og:site_name\" content=\"Centre for Computational Personalized Medicine\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/sano.science\/\" \/>\n<meta property=\"article:modified_time\" content=\"2024-01-15T12:32:32+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:site\" content=\"@sanoscience\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/sano.science\\\/research\\\/macrophage-resistance-to-ionizing-radiation-exposure-is-accompanied-by-decreased-cathepsin-d-and-increased-transferrin-receptor-1-expression\\\/\",\"url\":\"https:\\\/\\\/sano.science\\\/research\\\/macrophage-resistance-to-ionizing-radiation-exposure-is-accompanied-by-decreased-cathepsin-d-and-increased-transferrin-receptor-1-expression\\\/\",\"name\":\"Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression - 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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.<\/p>\n","innerContent":["\n<p class=\" eplus-wrapper\">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.<\/p>\n"]},{"blockName":"core\/spacer","attrs":{"height":"50px","epAnimationGeneratedClass":"edplus_anim-xsETDf","epGeneratedClass":"eplus-wrapper"},"innerBlocks":[],"innerHTML":"\n<div style=\"height:50px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n","innerContent":["\n<div style=\"height:50px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n"]},{"blockName":"acf\/button","attrs":{"title":"READ HERE","button_type":"link","url":"https:\/\/www.mdpi.com\/2072-6694\/15\/1\/270","button_style":"primary","target":"_blank","button_extra_classes":""},"innerBlocks":[],"innerHTML":"","innerContent":[]}],"meta_data":{"is_automatically_other_posts":true,"number_of_posts":"3","is_automatically_check_also_posts":true},"_links":{"self":[{"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research\/14895","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research"}],"about":[{"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/types\/research"}],"version-history":[{"count":2,"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research\/14895\/revisions"}],"predecessor-version":[{"id":14897,"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research\/14895\/revisions\/14897"}],"wp:attachment":[{"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/media?parent=14895"}],"wp:term":[{"taxonomy":"research_type","embeddable":true,"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research_type?post=14895"},{"taxonomy":"research_team","embeddable":true,"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research_team?post=14895"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}