Borane-protected phosphines are redox-active radioprotective agents for endothelial cells
| Autor: | Leonard A. Levin, Megan E. Crowe, Christopher J. Lieven, Alex F. Thompson, Nader Sheibani |
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| Rok vydání: | 2015 |
| Předmět: |
Radioprotection
Endothelial cells Clinical Biochemistry Disulfide reduction medicine.disease_cause Biochemistry Polyethylene Glycols chemistry.chemical_compound Superoxides Boranes MnTMPyP manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin Aorta Cells Cultured chemistry.chemical_classification Radiation biology Superoxide PB2 (3-propionic acid methyl ester)diphenylphosphine borane complex 3. Good health Toxicity PB1 bis(3-propionic acid methyl ester)phenylphosphine borane complex Oxidation-Reduction Signal Transduction Research Paper Radioprotective Agent Metalloporphyrins Phosphines TCEP tris(2-carboxyethyl)phosphine Phosphine–borane complexes Radiation-Protective Agents Superoxide dismutase PEG-SOD superoxide dismutase–polyethylene glycol from bovine erythrocytes ROS reactive oxygen species medicine Animals Humans Clonogenic assay Reactive oxygen species Superoxide Dismutase Organic Chemistry In vitro Mercaptoethylamines Clone Cells chemistry Gamma Rays biology.protein Biophysics Cattle BAEC bovine aortic endothelial cells Oxidative stress |
| Zdroj: | Redox Biology |
| ISSN: | 2213-2317 |
| Popis: | Exposure to radiation can damage endothelial cells in the irradiated area via the production of reactive oxygen species. We synthesized phosphine–borane complexes that reduce disulfide bonds and had previously been shown to interfere with redox-mediated signaling of cell death. We hypothesized that this class of drugs could interfere with the downstream effects of oxidative stress after irradiation and rescue endothelial cells from radiation damage. Cultured bovine aortic endothelial cells were plated for clonogenic assay prior to exposure to varying doses of irradiation from a 137Cs irradiator and treated with various concentrations of bis(3-propionic acid methyl ester)phenylphosphine borane complex (PB1) at different time points. The clone-forming ability of the irradiated cells was assessed seven days after irradiation. We compared the radioprotective effects of PB1 with the aminothiol radioprotectant WR1065 and known superoxide scavengers. PB1 significantly protected bovine aortic endothelial cells from radiation damage, particularly when treated both before and after radiation. The radioprotection with 1 µM PB1 corresponded to a dose-reduction factor of 1.24. Radioprotection by PB1 was comparable to the aminothiol WR1065, but was significantly less toxic and required much lower concentrations of drug (1 µM vs. 4 mM, respectively). Superoxide scavengers were not radioprotective in this paradigm, indicating the mechanisms for both loss of clonogenicity and PB1 radioprotection are independent of superoxide signaling. These data demonstrate that PB1 is an effective redox-active radioprotectant for endothelial cells in vitro, and is radioprotective at a concentration approximately 4 orders of magnitude lower than the aminothiol WR1065 with less toxicity. Graphical abstract Highlights • Phosphine–borane complexes (PB) reduce disulfide bonds and modulate redox signaling. • PB1 protects endothelial cells from radiation damage before and after radiation. • Radioprotection with PB1 is independent of superoxide signaling. • PB1 radioprotection is similar to WR1065, but with less toxicity and more potency. |
| Databáze: | OpenAIRE |
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