{"id":8386,"date":"2025-02-03T14:44:13","date_gmt":"2025-02-03T05:44:13","guid":{"rendered":"https:\/\/www.med.osaka-u.ac.jp\/eng\/?page_id=8386"},"modified":"2025-07-31T13:32:03","modified_gmt":"2025-07-31T04:32:03","slug":"inoue2025-2-3","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2025year\/inoue2025-2-3","title":{"rendered":"Hiromi Yamazaki, Daichi Inoue \u226aCancer Pathology\u226b <span>Selenoproteins: the fountain of youth?<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li><a href=\"https:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2025year\/inoue2025-2-3\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><span class=\"lineFrame\">Blood<\/span><\/p>\n<p><em>A team led by Osaka University researchers examines how antioxidant enzymes affect certain cell types and contribute to age-related diseases.<\/em><\/p>\n<p class=\"figure\"><a href=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig1.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-8699\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig1-400x341.jpg?_t=1737595747\" alt=\"\" width=\"600\" height=\"511\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig1-400x341.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig1-768x654.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig1.jpg 800w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><\/a><br \/>Figure 1. Selenoproteins safeguard stemness of hematopoietic stem cells and B-lineage maturation. Disrupted selenoprotein synthesis recapitulated aged phenotype. The accumulation of lipid peroxidation accelerated by aging occurs in specific cellular contexts and lineages. Under such oxidative stress, B cell progenitors acquire myeloid characteristics. (Created with BioRender.com)<\/p>\n<div class=\"TextBlock\">\n<p>Many foods are often advertised for their antioxidant properties. Antioxidants counteract what are known as reactive oxygen species (ROS), chemically reactive molecules that can disrupt the normal functions of lipids, proteins, and DNA in human cells. Accumulation of ROS contributes to the development of age-related diseases, including cancer, emphasizing the importance of keeping the oxidant\/antioxidant balance in check. In a recent article published in <em>Blood<\/em>, researchers from Osaka University and other institutions in Japan describe the key antioxidant role of molecules called selenoproteins and how disrupting their production can affect various cell types and hematopoiesis, which is the production of blood cells.<\/p>\n<p>Human cells have 25 different selenoproteins. These antioxidant enzymes help convert dangerous ROS, such as lipid peroxides, into a safer form. Buildup of lipid peroxides can affect critical cells called hematopoietic stem cells (HSCs), a phenomenon observed in aging diseases.\u00a0\u00a0<\/p>\n<p>\u201cWe observed that aged HSCs frequently display impaired selenoprotein synthesis, but it was unclear how this could contribute to cell aging and if it could be reversed,\u201d says Yumi Aoyama, co-lead author of the study. \u201cWe hypothesized that selenoproteins are a critical part of the antioxidant system that fights age-related changes in HSCs.\u201d<\/p>\n<p>To investigate this, the team used a mouse model with a certain gene knocked out, leading to disrupted selenoprotein production. They then examined how this affected different cell types, finding that the knockout negatively impacted HSCs and immune cells with B cell lineage (types of white blood cells) but had few effects on myeloid cells (a different family of immune cells).<\/p>\n<p>\u201cThe most notable results of the knockout included B lymphocytopenia, which means there were fewer B cells than expected,\u201d explains Hiromi Yamazaki, the other co-lead author. \u201cThe HSCs also had a limited ability to self-renew.\u201d<\/p>\n<p>These observations, along with increased expression levels of aging-related genes in these cell types, were consistent with what is frequently seen in age-related diseases. Further investigation indicated that the effects were driven by lipid peroxidation. Additionally, experiments with cells from the mouse model revealed that the disruption in selenoprotein synthesis could support B progenitors switching to the myeloid cell family.<\/p>\n<p>\u201cOur data suggest clear lineage-specific effects when the protective role of selenoproteins is lost,\u201d says Daichi Inoue, senior author of the study. \u201cThese enzymes are critical for counteracting the lipid peroxides that accumulate during the aging process.\u201d<\/p>\n<p>The researchers also investigated the mechanisms underlying hematopoiesis with a feeding experiment on the knockout mice. They revealed that dietary Vitamin E can protect hematopoiesis and has the ability to repair impaired B cell differentiation.<\/p>\n<p>This study shows the antioxidant functions of selenoproteins and how they ensure proper HSC self-renewal and B cell-lineage immune cell maturation. Because the knockout mice displayed similar phenotypes to aged normal mice, the findings demonstrate how potentially addressing selenoprotein production-related issues could help fight age-related diseases.<\/p>\n<\/div>\n<p>###<\/p>\n<p>The article, \u201cSelenoprotein-Mediated Redox Regulation Shapes the Cell Fate of HSCs and Mature Lineages,\u201d was published in <em>Blood<\/em> at DOI: <a href=\"https:\/\/doi.org\/10.1182\/blood.2024025402\">https:\/\/doi.org\/10.1182\/blood.2024025402<\/a>.<\/p>\n<p><strong>Summary:<\/strong> Researchers from Japan find that certain antioxidant enzymes, called selenoproteins, significantly contribute to fighting cell aging. The team used a gene knockout mouse model to help them study the effects of disrupting selenoprotein synthesis. This knockout negatively impacted hematopoietic stem cells and B cell-lineage immune cells, which was driven by the lack of selenoprotein-mediated fighting of lipid peroxides. These phenotypes mimic what is observed in age-related diseases, emphasizing the importance of selenoproteins in these disorders.<\/p>\n<p><strong>Tweet<\/strong>: New research uncovers how #antioxidant #enzymes called #selenoproteins are critically involved in preventing dangerous #age-related changes in cells @osaka_univ_e<\/p>\n<p><strong>Primary Keyword<\/strong>: Health and medicine<\/p>\n<p><strong>Additional Keyword<\/strong>:\u00a0Hematopoietic stem cells,\u00a0B lymphocytes,\u00a0Immune cells,\u00a0Antioxidants,\u00a0Reactive oxygen species,\u00a0Mouse models,\u00a0Cell death<\/p>\n<p><strong>Method of Research<\/strong>: Observational study<\/p>\n<p><strong>Subject of Research<\/strong>:\u00a0 Animals<\/p>\n<p class=\"figure\"><a href=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig2.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-8700\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig2-400x304.jpg?_t=1737595757\" alt=\"\" width=\"600\" height=\"455\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig2-400x304.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig2-768x583.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig2.jpg 850w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><\/a><br \/>Figure 2. <em>Trsp<\/em> gene deletion leads to disrupted selenoprotein synthesis. (Created with BioRender.com)<\/p>\n<div class=\"TextBlock\">\n<p class=\"figure\"><a href=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig3.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-8701\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig3-400x138.jpg?_t=1737595767\" alt=\"\" width=\"600\" height=\"208\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig3-400x138.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig3-768x266.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/01\/inoue_efig3.jpg 1000w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><\/a><br \/>Figure 3. Transplantation experiment of B progenitors from CD45.2<sup>+<\/sup> control or <em>Trsp<\/em> KO mice into lethally irradiated CD45.1<sup>+<\/sup> recipients. <em>Trsp<\/em> KO B progenitors demonstrated a significant potential to generate myeloid cells in the recipient bone marrow. (Created with BioRender.com)<\/p>\n<\/div>\n<div class=\"TextBlock\">\n<p>Title: \u201cSelenoprotein-Mediated Redox Regulation Shapes the Cell Fate of HSCs and Mature Lineages\u201d<\/p>\n<\/div>\n<p>Journal: <em>Blood<\/em><em><br \/><\/em>Authors: Yumi Aoyama, Hiromi Yamazaki, Koutarou Nishimura, Masaki Nomura, Tsukasa Shigehiro, Takafumi Suzuki, Weijia Zang, Yota Tatara, Hiromi Ito, Yasutaka Hayashi, Yui Koike, Miki Fukumoto, Atsushi Tanaka, Yifan Zhang, Wataru Saika, Chihiro Hasegawa, Shuya Kasai, Yingyi Kong, Yohei Minakuchi,\u00a0Ken Itoh, Masayuki Yamamoto, Shinya Toyokuni, Atsushi Toyoda, Tomokatsu Ikawa, Akifumi Takaori-Kondo, Daichi Inoue.<br \/>DOI: <span lang=\"EN-US\"><a href=\"https:\/\/doi.org\/10.1182\/blood.2024025402\" target=\"_blank\" rel=\"noopener\">10.1182\/blood.2024025402<\/a><\/span><\/p>\n<p>Japan Society for the Promotion of Science (JSPS),<br \/>\u00a0Japan Agency for Medical Research and Development (AMED),<br \/>Japan Science and Technology Agency (JST)<br \/>The Naito Foundation,<br \/>American Society of Hematology,<br \/>Japanese Society of Hematology,<br \/>ONO Medical Research Foundation,<br \/>Ono Pharmaceutical Foundation for Oncology,<br \/>The Mitsubishi Foundation,<br \/>The Cell Science Research Foundation,<br \/>Kobayashi Foundation for Cancer Research,<br \/>Takeda Science Foundation,<br \/>Chugai Foundation for Innovative Drug Discovery Science,<br \/>Foundation for Promotion of Cancer Research,<br \/>Friends of Leukemia Research Fund,<br \/>Princess Takamatsu Cancer Research Fund,<br \/>Mochida Memorial Foundation for Medical and Pharmaceutical Research,<br \/>and MSD Life Science Foundation and Public Interest Incorporated Foundation,<br \/>SENSHIN Medical Research Foundation<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Blood A team led by Osaka University researchers examines how antioxidant enzymes affect cert [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":8699,"parent":8696,"menu_order":31,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8386"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=8386"}],"version-history":[{"count":11,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8386\/revisions"}],"predecessor-version":[{"id":9193,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8386\/revisions\/9193"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8696"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/8699"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=8386"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}