Tocol Prophylaxis for Total-body Irradiation: A Proteomic Analysis in Murine Model
| Autor: | V. Ashutosh Rao, Vijay K. Singh, Oluseyi O. Fatanmi, Stephen Y. Wise, Elliot T. Rosen |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Proteomics RHOA Epidemiology Health Toxicology and Mutagenesis Tocopherols Radiation-Protective Agents GTPase Pharmacology Mass Spectrometry 030218 nuclear medicine & medical imaging Jejunum Mice 03 medical and health sciences Radiation Protection 0302 clinical medicine Mouse Jejunum medicine Animals Radiology Nuclear Medicine and imaging Radiation Injuries biology Chemistry Total body irradiation Actin cytoskeleton Actin Cytoskeleton Disease Models Animal medicine.anatomical_structure Gene Expression Regulation Gamma Rays Murine model 030220 oncology & carcinogenesis biology.protein Signal transduction Whole-Body Irradiation |
| Zdroj: | Health Physics. 119:12-20 |
| ISSN: | 1538-5159 0017-9078 |
| DOI: | 10.1097/hp.0000000000001221 |
| Popis: | The aim of this study was to analyze the changes in mouse jejunum protein expression in response to prophylactic administration of two promising tocols, γ-tocotrienol (GT3) and α-tocopherol succinate (TS), as radiation countermeasures before irradiation to elucidate the molecular mechanism(s) of their radioprotective efficacy. Mice were administered GT3 or TS (200 mg kg) subcutaneously 24 h prior to exposure to 11 Gy Co γ-radiation, a supralethal dose for mice. Jejunum was harvested 24 h post-irradiation. Results of the two-dimensional differential in-gel electrophoresis (2D-DIGE), coupled with mass spectrometry, and advanced bioinformatics tools suggest that the tocols have a corresponding impact on expression of 13 proteins as identified by mass spectrometry. Ingenuity Pathway Analysis (IPA) reveals a network of associated proteins involved in inflammatory response, organismal injury and abnormalities, and cellular development. Relevant signaling pathways including actin cytoskeleton signaling, RhoA signaling, and Rho family GTPase were identified. This study reveals the major proteins, pathways, and networks involved in preventing the radiation-induced injury in gut that may be contributing to enhanced survival. |
| Databáze: | OpenAIRE |
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