ArticlePloS one2015
Thrombomodulin contributes to gamma tocotrienol-mediated lethality protection and hematopoietic cell recovery in irradiated mice.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 24 citations in OpenAlex.
- Radiation Countermeasure Gamma-Tocotrienol Inhibits Accumulation of Lipid Peroxidation Products in the Serum of Nonhuman Primates Exposed to Partial- or Total-Body Radiation-A Hallmark of Inhibition of Irradiation-Induced Ferroptosis?International journal of molecular sciences · 2026Article
- Radiomitigators: Breakthroughs in Post-Radiation Recovery.Antioxidants (Basel, Switzerland) · 2026Review
- Geranylgeranyl Transferase Inhibitors Mitigate Intestinal Radiation Toxicity.International journal of radiation oncology, biology, physics · 2026Article
- Tocotrienols Provide Radioprotection to Multiple Organ Systems through Complementary Mechanisms of Antioxidant and Signaling Effects.Antioxidants (Basel, Switzerland) · 2023Review
- Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry.Antioxidants (Basel, Switzerland) · 2022Review
- Mitigation of late cardiovascular effects of oxygen ion radiation by γ-tocotrienol in a mouse model.Life sciences in space research · 2021Article
- Pathomechanisms and therapeutic opportunities in radiation-induced heart disease: from bench to bedside.Clinical research in cardiology : official journal of the German Cardiac Society · 2021Review
- Fractionated radiation suppresses Kruppel-like factor 2 pathway to a greater extent than by single exposure to the same total dose.Scientific reports · 2020Article
- Therapeutic potential of natural plant products and their metabolites in preventing radiation enteropathy resulting from abdominal or pelvic irradiation.International journal of radiation biology · 2019Review
- Gamma-Tocotrienol Protects the Intestine from Radiation Potentially by Accelerating Mesenchymal Immune Cell Recovery.Antioxidants (Basel, Switzerland) · 2019Article
- Utilization of Vitamin E Analogs to Protect Normal Tissues While Enhancing Antitumor Effects.Seminars in radiation oncology · 2019Review
- Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury.Antioxidants (Basel, Switzerland) · 2018Article
- Antioxidant Supplementation: A Linchpin in Radiation-Induced Enteritis.Technology in cancer research & treatment · 2017Article
- Variable phenotypic penetrance of thrombosis in adult mice after tissue-selective and temporally controlled Thbd gene inactivation.Blood advances · 2017Article
- The Vitamin E Analog Gamma-Tocotrienol (GT3) and Statins Synergistically Up-Regulate Endothelial Thrombomodulin (TM).International journal of molecular sciences · 2016Article
- Novel concepts in radiation-induced cardiovascular disease.World journal of cardiology · 2016Review
- The Vitamin E Analog Gamma-Tocotrienol (GT3) Suppresses Radiation-Induced Cytogenetic Damage.Pharmaceutical research · 2016Article
- Understanding the Pathophysiology and Challenges of Development of Medical Countermeasures for Radiation-Induced Vascular/Endothelial Cell Injuries: Report of a NIAID Workshop, August 20, 2015.Radiation research · 2016Article
- Ionizing Radiation-Induced Endothelial Cell Senescence and Cardiovascular Diseases.Radiation research · 2016Review
- γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status.International journal of molecular sciences · 2016Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Systemic administration of recombinant thrombomodulin (TM) confers radiation protection partly by accelerating hematopoietic recovery. The uniquely potent radioprotector gamma tocotrienol (GT3), in addition to being a strong antioxidant, inhibits the enzyme hydroxy-methyl-glutaryl-coenzyme A reductase (HMGCR) and thereby likely modulates the expression of TM. We hypothesized that the mechanism underlying the exceptional radioprotective properties of GT3 partly depends on the presence of endothelial TM. In vitro studies confirmed that ionizing radiation suppresses endothelial TM (about 40% at 4 hr after 5 Gy γ-irradiation) and that GT3 induces TM expression (about 2 fold at the mRNA level after 5 μM GT3 treatment for 4 hr). In vivo survival studies showed that GT3 was significantly more effective as a radioprotector in TM wild type (TM+/+) mice than in mice with low TM function (TMPro/-). After exposure to 9 Gy TBI, GT3 pre-treatment conferred 85% survival in TM+/+ mice compared to only 50% in TMPro/-. Thus, GT3-mediated radiation lethality protection is partly dependent on endothelial TM. Significant post-TBI recovery of hematopoietic cells, particularly leukocytes, was observed in TM+/+ mice (p = 0.003), but not in TMPro/- mice, despite the fact that GT3 induced higher levels of granulocyte colony stimulating factor (G-CSF) in TMPro/- mice (p = 0.0001). These data demonstrate a critical, G-CSF-independent, role for endothelial TM in GT3-mediated lethality protection and hematopoietic recovery after exposure to TBI and may point to new strategies to enhance the efficacy of current medical countermeasures in radiological/nuclear emergencies.
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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.