ArticleRadiation research2011
Geldanamycin analog 17-DMAG limits apoptosis in human peripheral blood cells by inhibition of p53 activation and its interaction with heat-shock protein 90 kDa after exposure to ionizing radiation.
Article in Radiation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
- Co-Therapy of Pegylated G-CSF and Ghrelin for Enhancing Survival After Exposure to Lethal Radiation.Frontiers in pharmacology · 2021Article
- Circulating Cytokine/Chemokine Concentrations Respond to Ionizing Radiation Doses but not Radiation Dose Rates: Granulocyte-Colony Stimulating Factor and Interleukin-18.Radiation research · 2018Article
- Regulation of Apoptosis During Porcine Circovirus Type 2 Infection.Frontiers in microbiology · 2018Review
- Combined Therapy of Pegylated G-CSF and Alxn4100TPO Improves Survival and Mitigates Acute Radiation Syndrome after Whole-Body Ionizing Irradiation Alone and Followed by Wound Trauma.Radiation research · 2017Article
- Thrombopoietin Receptor Agonist Mitigates Hematopoietic Radiation Syndrome and Improves Survival after Whole-Body Ionizing Irradiation Followed by Wound Trauma.Mediators of inflammation · 2017Article
- Cellular Pathways in Response to Ionizing Radiation and Their Targetability for Tumor Radiosensitization.International journal of molecular sciences · 2016Review
- HSP90AB1: Helping the good and the bad.Gene · 2016Review
- Ciprofloxacin as a potential radio-sensitizer to tumor cells and a radio-protectant for normal cells: differential effects on γ-H2AX formation, p53 phosphorylation, Bcl-2 production, and cell death.Molecular and cellular biochemistry · 2014Article
- Ciprofloxacin increases survival after ionizing irradiation combined injury: γ-H2AX formation, cytokine/chemokine, and red blood cells.Health physics · 2014Article
- Down-regulation of heat shock protein HSP90ab1 in radiation-damaged lung cells other than mast cells.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2014Article
- Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks splenomegaly, and improves survival after whole-body ionizing irradiation but not after irradiation combined with burn.Oxidative medicine and cellular longevity · 2014Article
- PU-H71 effectively induces degradation of IκB kinase β in the presence of TNF-α.Molecular and cellular biochemistry · 2014Article
- Radioprotective effects of oral 17-dimethylaminoethylamino-17-demethoxygeldanamycin in mice: bone marrow and small intestine.Cell & bioscience · 2013Article
- Combined effects of 17-DMAG and TNF on cells through a mechanism related to the NF-kappaB pathway.Diagnostic pathology · 2013Article
- Article
- Combination therapy with HSP90 inhibitor 17-DMAG reconditions the tumor microenvironment to improve recruitment of therapeutic T cells.Cancer research · 2012Article
- Wound trauma alters ionizing radiation dose assessment.Cell & bioscience · 2012Article
- 17-DMAG diminishes hemorrhage-induced small intestine injury by elevating Bcl-2 protein and inhibiting iNOS pathway, TNF-α increase, and caspase-3 activation.Cell & bioscience · 2011Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Exposure to ionizing radiation induces p53, and its inhibition improves mouse survival. We tested the effect of 17-dimethylamino-ethylamino-17-demethoxygeldanamycin (17-DMAG) on p53 expression and function after radiation exposure. 17-DMAG, a heat-shock protein 90 (Hsp90) inhibitor, protects human T cells from ionizing radiation-induced apoptosis by inhibiting inducible nitric oxide synthase (iNOS) and subsequent caspase-3 activation. Using ex vivo human peripheral blood mononuclear cells, we found that ionizing radiation increased p53 accumulation, acute p53 phosphorylation, Bax expression and caspase-3/7 activation in a radiation dose- and time postirradiation-dependent manner. 17-DMAG inhibited these increases in a concentration-dependent manner (IC(50) = 0.93 ± 0.01 µM). Using in vitro models, we determined that inhibition of p53 by genetic knockout resulted in lower levels of caspase-3/7 activity 1 day after irradiation and enhanced survival at 10 days. Analysis of p53-Hsp90 interaction in ex vivo cell lysates indicated that the binding between the two molecules occurred after irradiation but 17-DMAG prevented the binding. Taken together, these results suggest the presence of p53 phosphorylation and Hsp90-dependent p53 stabilization after acute irradiation. Hsp90 inhibitors such as 17-DMAG may prove useful with radiation-based cancer therapy as well as for general radioprotection.
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