Serum microRNA profile of rhesus macaques following ionizing radiation exposure and treatment with a medical countermeasure, Ex-Rad.

Autor: Russ E; Division of Radioprotectants, Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.; Graduate Program of Cellular and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.; Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA., Fatanmi OO; Division of Radioprotectants, Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.; Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA., Wise SY; Division of Radioprotectants, Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.; Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA., Carpenter AD; Division of Radioprotectants, Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.; Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA., Maniar M; Onconova Therapeutics, Inc., Newtown, PA, 18940, USA.; Palm Pharmaceuticals, Inc, 46750 Sentinel Drive, Fremont, CA, 94539, USA., Iordanskiy S; Division of Radioprotectants, Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. sergey.iordanskiy@usuhs.edu.; Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. sergey.iordanskiy@usuhs.edu., Singh VK; Division of Radioprotectants, Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. vijay.singh@usuhs.edu.; Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. vijay.singh@usuhs.edu.; Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, 4301 Jones Bridge Road, Bethesda, MD, 20814-2712, USA. vijay.singh@usuhs.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Feb 24; Vol. 14 (1), pp. 4518. Date of Electronic Publication: 2024 Feb 24.
DOI: 10.1038/s41598-024-54997-8
Abstrakt: Exposure to ionizing radiation (IR) presents a formidable clinical challenge. Total-body or significant partial-body exposure at a high dose and dose rate leads to acute radiation syndrome (ARS), the complex pathologic effects that arise following IR exposure over a short period of time. Early and accurate diagnosis of ARS is critical for assessing the exposure dose and determining the proper treatment. Serum microRNAs (miRNAs) may effectively predict the impact of irradiation and assess cell viability/senescence changes and inflammation. We used a nonhuman primate (NHP) model-rhesus macaques (Macaca mulatta)-to identify the serum miRNA landscape 96 h prior to and following 7.2 Gy total-body irradiation (TBI) at four timepoints: 24, 36, 48, and 96 h. To assess whether the miRNA profile reflects the therapeutic effect of a small molecule ON01210, commonly known as Ex-Rad, that has demonstrated radioprotective efficacy in a rodent model, we administered Ex-Rad at two different schedules of NHPs; either 36 and 48 h post-irradiation or 48 and 60 h post-irradiation. Results of this study corroborated our previous findings obtained using a qPCR array for several miRNAs and their modulation in response to irradiation: some miRNAs demonstrated a temporary increased serum concentration within the first 24-36 h (miR-375, miR-185-5p), whereas others displayed either a prolonged decline (miR-423-5p) or a long-term increase (miR-30a-5p, miR-27b-3p). In agreement with these time-dependent changes, hierarchical clustering of differentially expressed miRNAs showed that the profiles of the top six miRNA that most strongly correlated with radiation exposure were inconsistent between the 24 and 96 h timepoints following exposure, suggesting that different biodosimetry miRNA markers might be required depending on the time that has elapsed. Finally, Ex-Rad treatment restored the level of several miRNAs whose expression was significantly changed after radiation exposure, including miR-16-2, an miRNA previously associated with radiation survival. Taken together, our findings support the use of miRNA expression as an indicator of radiation exposure and the use of Ex-Rad as a potential radioprotectant.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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