ArticleThe Journal of biological chemistry2013
Deoxyhypusine synthase promotes differentiation and proliferation of T helper type 1 (Th1) cells in autoimmune diabetes.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes.Cell reports. Medicine · 2023Trial
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Using animal models to decipher the role of polyamines in the pancreas and β Cell.Amino acids · 2026Review
- eIF5A and hypusination-related disorders: literature review and case report of DOHH-related encephalopathy.Journal of neurodevelopmental disorders · 2025Review
- Conversion of T Effector Cells Into T Regulatory Cells in Type 1 Diabetes/Latent Autoimmune Diabetes of Adults by Inhibiting eIF5A and Notch Pathways.ImmunoTargets and therapy · 2025Article
- Manipulation of DHPS activity affects dendritic morphology and expression of synaptic proteins in primary rat cortical neurons.Frontiers in cellular neuroscience · 2024Article
- Amino acid metabolism reprogramming: shedding new light on T cell anti-tumor immunity.Journal of experimental & clinical cancer research : CR · 2023Review
- Translation factor eIF5a is essential for IFNγ production and cell cycle regulation in primary CD8Nature communications · 2022Article
- Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis.Endocrinology · 2022Review
- Roles of eIF5A in the immunosurveillance of cellular senescence.Cancer biology & medicine · 2022Article
- Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder.American journal of human genetics · 2022Article
- Role of Polyamines and Hypusine in β Cells and Diabetes Pathogenesis.Metabolites · 2022Review
- Investigation of an Allosteric Deoxyhypusine Synthase Inhibitor inMolecules (Basel, Switzerland) · 2022Article
- The eukaryotic initiation factor 5A (eIF5A1), the molecule, mechanisms and recent insights into the pathophysiological roles.Cell & bioscience · 2021Review
- Deoxyhypusine synthase promotes a pro-inflammatory macrophage phenotype.Cell metabolism · 2021Article
- Deoxyhypusine synthase, an essential enzyme for hypusine biosynthesis, is required for proper exocrine pancreas development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Inhibition of eIF5A hypusination reprogrammes metabolism and glucose handling in mouse kidney.Cell death & disease · 2021Article
- Immune Cell Plasticity Allows for Resetting of Phenotype From Effector to Regulator With Combined Inhibition of Notch/eIF5A Pathways.Frontiers in cell and developmental biology · 2021Article
- Recent insights into eukaryotic translation initiation factors 5A1 and 5A2 and their roles in human health and disease.Cancer cell international · 2020Review
- Adiponectin receptor fragmentation in mouse models of type 1 and type 2 diabetes.Archives of autoimmune diseases · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
In type 1 diabetes, cytokines arising from immune cells cause islet β cell dysfunction even before overt hyperglycemia. Deoxyhypusine synthase catalyzes the crucial hypusine modification of the factor eIF5A, which promotes the translation of a subset of mRNAs involved in cytokine responses. Here, we tested the hypothesis that deoxyhypusine synthase and, secondarily, hypusinated eIF5A contribute to the pathogenesis of type 1 diabetes using the non-obese diabetic (NOD) mouse model. Pre-diabetic NOD mice that received injections of the deoxyhypusine inhibitor N1-guanyl-1,7-diaminoheptane (GC7) demonstrated significantly improved glucose tolerance, more robust insulin secretion, and reduced insulitis compared with control animals. Analysis of tissues from treated mice revealed selective reductions in diabetogenic T helper type 1 (Th1) cells in the pancreatic lymph nodes, a primary site of antigen presentation. Isolated mouse CD90.2(+) splenocytes stimulated in vitro with anti-CD3/anti-CD28 and IL-2 to mimic autoimmune T cell activation exhibited proliferation and differentiation of CD4(+) T cell subsets (Th1, Th17, and Treg), but those treated with the deoxyhypusine synthase inhibitor GC7 showed a dose-dependent block in T cell proliferation with selective reduction in Th1 cells, similar to that observed in NOD mice. Inhibition of deoxyhypusine synthase blocked post-transcriptional expression of CD25, the high affinity IL-2 receptor α chain. Our results suggest a previously unrecognized role for deoxyhypusine synthase in promoting T cell proliferation and differentiation via regulation of CD25. Inhibition of deoxyhypusine synthase may provide a strategy for reducing diabetogenic Th1 cells and preserving β cell function in type 1 diabetes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.