ArticleAmerican journal of physiology. Endocrinology and metabolism2014
Eukaryotic translation initiation factor 5A inhibition alters physiopathology and immune responses in a "humanized" transgenic mouse model of type 1 diabetes.
Article in American journal of physiology. Endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Translational Control in Cardiac Pathophysiology and Therapeutic Development: When mRNA Meets the Heart.International journal of molecular sciences · 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
- The Many Faces of Hypusinated eIF5A: Cell Context-Specific Effects of the Hypusine Circuit and Implications for Human Health.International journal of molecular sciences · 2024Review
- The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70s.Amino acids · 2023Article
- Preclinical Models to Evaluate the Human Response to Autoantigen and Antigen-Specific Immunotherapy in Human Type 1 Diabetes.Frontiers in endocrinology · 2022Review
- The eukaryotic initiation factor 5A (eIF5A1), the molecule, mechanisms and recent insights into the pathophysiological roles.Cell & bioscience · 2021Review
- Inhibition of eIF5A hypusination pathway as a new pharmacological target for stroke therapy.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- eIF5A inhibition influences T cell dynamics in the pancreatic microenvironment of the humanized mouse model of Type 1 Diabetes.Scientific reports · 2019Article
- Insulin action on protein synthesis and its association with eIF5A expression and hypusination.Molecular biology reports · 2019Article
- Hypusination of eIF5A as a Target for Antiviral Therapy.DNA and cell biology · 2017Article
- Targeting the polyamine-hypusine circuit for the prevention and treatment of cancer.Amino acids · 2016Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Therapeutic options for treatment of type 1 diabetes (T1D) are still missing. New avenues for immune modulation need to be developed. Here we attempted at altering the diabetes outcome of our humanized model of T1D by inhibiting translation-initiation factor eIF5A hypusination in vivo. Double-transgenic (DQ8-GAD65) mice were immunized with adenoviral vectors carrying GAD65 for diabetes induction. Animals were subsequently treated with deoxyhypusine synthase (DHS) inhibitor GC7 and monitored for diabetes development over time. On one hand, helper CD4(+) T cells were clearly affected by the downregulation of the eIF5A not just at the pancreas level but overall. On the other hand, the T regulatory cell component of CD4 responded with activation and proliferation significantly higher than in the non-GC7-treated controls. Female mice seemed to be more susceptible to these effects. All together, our results show for the first time that downregulation of eIF5A through inhibition of DHS altered the physiopathology and observed immune outcome of diabetes in an animal model that closely resembles human T1D. Although the development of diabetes could not be abrogated by DHS inhibition, the immunomodulatory capacity of this approach may supplement other interventions directed at increasing regulation of autoreactive T cells in T1D.
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Registered trials
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.