Proinflammatory Cytokines Perturb Mouse and Human Pancreatic Islet Circadian Rhythmicity and Induce Uncoordinated β-Cell Clock Gene Expression via Nitric Oxide, Lysine Deacetylases, and Immunoproteasomal Activity
| العنوان: | Proinflammatory Cytokines Perturb Mouse and Human Pancreatic Islet Circadian Rhythmicity and Induce Uncoordinated β-Cell Clock Gene Expression via Nitric Oxide, Lysine Deacetylases, and Immunoproteasomal Activity |
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| المؤلفون: | Nico Fischer, Tina Dahlby, Melissa Koomen, Thomas Mandrup-Poulsen, Charna Dibner, Volodymyr Petrenko, Phillip Alexander Keller Andersen, Seyed Mojtaba Ghiasi, Peter Horskjær Rose |
| المصدر: | International Journal of Molecular Sciences Andersen, P A K, Petrenko, V, Rose, P H, Koomen, M, Fischer, N, Ghiasi, S M, Dahlby, T, Dibner, C & Mandrup-Poulsen, T 2021, ' Proinflammatory cytokines perturb mouse and human pancreatic islet circadian rhythmicity and induce uncoordinated β-cell clock gene expression via nitric oxide, lysine deacetylases, and immunoproteasomal activity ', International Journal of Molecular Sciences, vol. 22, no. 1, 83, pp. 1-25 . https://doi.org/10.3390/ijms22010083Test International Journal of Molecular Sciences, Vol. 22, No 1 (2020) P. 83 Volume 22 Issue 1 International Journal of Molecular Sciences, Vol 22, Iss 83, p 83 (2021) |
| بيانات النشر: | MDPI, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Interferon-gamma/metabolism/pharmacology, lcsh:Chemistry, Mice, 0302 clinical medicine, ARNTL Transcription Factors/genetics/metabolism, Insulin-Secreting Cells, Insulin, immuno-metabolism, lcsh:QH301-705.5, Spectroscopy, Cells, Cultured, ddc:616, Tumor, Cultured, diabetes, Chemistry, nitric oxide synthase, Diabetes, ARNTL Transcription Factors, General Medicine, Computer Science Applications, 3. Good health, Cell biology, Circadian Rhythm, CLOCK, PER2, medicine.anatomical_structure, Knockout mouse, Epigenetics, Female, Proteasome Endopeptidase Complex, Insulin/metabolism, Cells, Period (gene), Insulin-Secreting Cells/drug effects/metabolism, 030209 endocrinology & metabolism, Nitric Oxide, Catalysis, Article, Histone Deacetylases, Cell Line, Proinflammatory cytokine, Inorganic Chemistry, 03 medical and health sciences, Interferon-gamma, Reactive Oxygen Species/metabolism, Cell Line, Tumor, medicine, biochemistry, Animals, Humans, Viability assay, Physical and Theoretical Chemistry, ddc:612, Molecular Biology, epigenetics, Pancreatic islets, Nitric oxide synthase, Organic Chemistry, HDAC3, Proteasome Endopeptidase Complex/metabolism, 030104 developmental biology, HEK293 Cells, lcsh:Biology (General), lcsh:QD1-999, Nitric Oxide/metabolism, Histone Deacetylases/metabolism, chronobiology, Reactive Oxygen Species, Chronobiology, Immuno-metabolism |
| الوصف: | Pancreatic &beta cell-specific clock knockout mice develop &beta cell oxidative-stress and failure, as well as glucose-intolerance. How inflammatory stress affects the cellular clock is under-investigated. Real-time recording of Per2:luciferase reporter activity in murine and human pancreatic islets demonstrated that the proinflammatory cytokine interleukin-1&beta (IL-1&beta ) lengthened the circadian period. qPCR-profiling of core clock gene expression in insulin-producing cells suggested that the combination of the proinflammatory cytokines IL-1&beta and interferon-&gamma (IFN-&gamma ) caused pronounced but uncoordinated increases in mRNA levels of multiple core clock genes, in particular of reverse-erythroblastosis virus &alpha (Rev-erb&alpha ), in a dose- and time-dependent manner. The REV-ERB&alpha /&beta agonist SR9009, used to mimic cytokine-mediated Rev-erb&alpha induction, reduced constitutive and cytokine-induced brain and muscle arnt-like 1 (Bmal1) mRNA levels in INS-1 cells as expected. SR9009 induced reactive oxygen species (ROS), reduced insulin-1/2 (Ins-1/2) mRNA and accumulated- and glucose-stimulated insulin secretion, reduced cell viability, and increased apoptosis levels, reminiscent of cytokine toxicity. In contrast, low (< 5,0 &mu M) concentrations of SR9009 increased Ins-1 mRNA and accumulated insulin-secretion without affecting INS-1 cell viability, mirroring low-concentration IL-1&beta mediated &beta cell stimulation. Inhibiting nitric oxide (NO) synthesis, the lysine deacetylase HDAC3 and the immunoproteasome reduced cytokine-mediated increases in clock gene expression. In conclusion, the cytokine-combination perturbed the intrinsic clocks operative in mouse and human pancreatic islets and induced uncoordinated clock gene expression in INS-1 cells, the latter effect associated with NO, HDAC3, and immunoproteasome activity. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::57f713196105e260c2898cb08ff9e574Test http://europepmc.org/articles/PMC7795908Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....57f713196105e260c2898cb08ff9e574 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 16616596 |
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