Circadian synchronization differentially modifies cytokine-mediated transcriptomic remodeling and cell death in INS-1 cells and mouse islets
Summary: Perturbation of the β-cell circadian clock causes oxidative stress and secretory failure, and proinflammatory cytokines disrupt the β-cell core clock. We hypothesized that cytokine-mediated clock perturbation in β-cells depends on circadian synchronization status. Cytokine-mediated core clo...
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Elsevier
2025-05-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225006923 |
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| author | Phillip Alexander Keller Andersen Rasmus H. Reeh Isabel Sanders Emilie Bender Overlund Georgia Katsioudi Cecilia Jiménez-Sánchez Emil Zeng Skovhøj Anniek Frederike Lubberding Charna Dibner Thomas Mandrup-Poulsen |
| author_facet | Phillip Alexander Keller Andersen Rasmus H. Reeh Isabel Sanders Emilie Bender Overlund Georgia Katsioudi Cecilia Jiménez-Sánchez Emil Zeng Skovhøj Anniek Frederike Lubberding Charna Dibner Thomas Mandrup-Poulsen |
| author_sort | Phillip Alexander Keller Andersen |
| collection | DOAJ |
| description | Summary: Perturbation of the β-cell circadian clock causes oxidative stress and secretory failure, and proinflammatory cytokines disrupt the β-cell core clock. We hypothesized that cytokine-mediated clock perturbation in β-cells depends on circadian synchronization status. Cytokine-mediated core clock mRNA expression in non-synchronized insulin-producing INS-1 cells were potentiated upon synchronization, which were differentially translated into alterations in protein levels. Synchronization sensitized INS-1 cells to cytokine-mediated cytotoxicity, associated with potentiation of NF-κB activity. Inhibition of NF-κB abrogated cytokine-mediated clock gene-expression independent of synchronization status and reversed cytokine-mediated period lengthening. In contrast, in murine islets, cytokines generally reduced core clock mRNA expression independently of synchronization status or NF-κB activity. Synchronization prevented cytokine-mediated cytotoxicity, but not NF-κB activity to a degree comparable to that of KINK-1, while alterations in islet rhythmicity were unaffected by NF-κB inhibition. In conclusion, circadian synchronization differentially modifies cytokine-mediated transcriptomic remodeling and cell death in INS-1 cells and murine islets, depending on NF-κB involvement. |
| format | Article |
| id | doaj-art-219e7bef4fa441a4af641c3cfcf51411 |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-219e7bef4fa441a4af641c3cfcf514112025-08-20T02:20:13ZengElsevieriScience2589-00422025-05-0128511243110.1016/j.isci.2025.112431Circadian synchronization differentially modifies cytokine-mediated transcriptomic remodeling and cell death in INS-1 cells and mouse isletsPhillip Alexander Keller Andersen0Rasmus H. Reeh1Isabel Sanders2Emilie Bender Overlund3Georgia Katsioudi4Cecilia Jiménez-Sánchez5Emil Zeng Skovhøj6Anniek Frederike Lubberding7Charna Dibner8Thomas Mandrup-Poulsen9Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark; Corresponding authorDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, DenmarkDepartment of Surgery, Division of Thoracic and Endocrine Surgery, University Hospitals of Geneva, 1211 Geneva, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics of Geneva (iGE3), 1211 Geneva, SwitzerlandDepartment of Surgery, Division of Thoracic and Endocrine Surgery, University Hospitals of Geneva, 1211 Geneva, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics of Geneva (iGE3), 1211 Geneva, SwitzerlandDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, DenmarkDepartment of Surgery, Division of Thoracic and Endocrine Surgery, University Hospitals of Geneva, 1211 Geneva, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics of Geneva (iGE3), 1211 Geneva, SwitzerlandDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, DenmarkSummary: Perturbation of the β-cell circadian clock causes oxidative stress and secretory failure, and proinflammatory cytokines disrupt the β-cell core clock. We hypothesized that cytokine-mediated clock perturbation in β-cells depends on circadian synchronization status. Cytokine-mediated core clock mRNA expression in non-synchronized insulin-producing INS-1 cells were potentiated upon synchronization, which were differentially translated into alterations in protein levels. Synchronization sensitized INS-1 cells to cytokine-mediated cytotoxicity, associated with potentiation of NF-κB activity. Inhibition of NF-κB abrogated cytokine-mediated clock gene-expression independent of synchronization status and reversed cytokine-mediated period lengthening. In contrast, in murine islets, cytokines generally reduced core clock mRNA expression independently of synchronization status or NF-κB activity. Synchronization prevented cytokine-mediated cytotoxicity, but not NF-κB activity to a degree comparable to that of KINK-1, while alterations in islet rhythmicity were unaffected by NF-κB inhibition. In conclusion, circadian synchronization differentially modifies cytokine-mediated transcriptomic remodeling and cell death in INS-1 cells and murine islets, depending on NF-κB involvement.http://www.sciencedirect.com/science/article/pii/S2589004225006923Cell biologyTranscriptomics |
| spellingShingle | Phillip Alexander Keller Andersen Rasmus H. Reeh Isabel Sanders Emilie Bender Overlund Georgia Katsioudi Cecilia Jiménez-Sánchez Emil Zeng Skovhøj Anniek Frederike Lubberding Charna Dibner Thomas Mandrup-Poulsen Circadian synchronization differentially modifies cytokine-mediated transcriptomic remodeling and cell death in INS-1 cells and mouse islets iScience Cell biology Transcriptomics |
| title | Circadian synchronization differentially modifies cytokine-mediated transcriptomic remodeling and cell death in INS-1 cells and mouse islets |
| title_full | Circadian synchronization differentially modifies cytokine-mediated transcriptomic remodeling and cell death in INS-1 cells and mouse islets |
| title_fullStr | Circadian synchronization differentially modifies cytokine-mediated transcriptomic remodeling and cell death in INS-1 cells and mouse islets |
| title_full_unstemmed | Circadian synchronization differentially modifies cytokine-mediated transcriptomic remodeling and cell death in INS-1 cells and mouse islets |
| title_short | Circadian synchronization differentially modifies cytokine-mediated transcriptomic remodeling and cell death in INS-1 cells and mouse islets |
| title_sort | circadian synchronization differentially modifies cytokine mediated transcriptomic remodeling and cell death in ins 1 cells and mouse islets |
| topic | Cell biology Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225006923 |
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