Plasma Derived Exosomal Biomarkers of Exposure to Ionizing Radiation in Nonhuman Primates
Autor: | Vijay K. Singh, Briana K Hanlon, Khyati Y. Mehta, Melissa Garcia, Charles P. Hinzman, Oluseyi O. Fatanmi, Amrita K. Cheema |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male gamma-radiation nonhuman primates Inflammation exosomes medicine.disease_cause Catalysis Article Ionizing radiation Inorganic Chemistry lcsh:Chemistry 03 medical and health sciences Metabolomics Liquid chromatography–mass spectrometry Radiation Ionizing medicine Metabolome Animals lipidomes Physical and Theoretical Chemistry Least-Squares Analysis Molecular Biology lcsh:QH301-705.5 Spectroscopy metabolites plasma Chemistry Organic Chemistry Discriminant Analysis General Medicine Lipid Metabolism Macaca mulatta Microvesicles Computer Science Applications 030104 developmental biology Biochemistry lcsh:Biology (General) lcsh:QD1-999 Biomarker (medicine) biomarker Female medicine.symptom Oxidative stress Biomarkers |
Zdroj: | International Journal of Molecular Sciences, Vol 19, Iss 11, p 3427 (2018) International Journal of Molecular Sciences Volume 19 Issue 11 |
ISSN: | 1422-0067 |
Popis: | Exposure to ionizing radiation induces a cascade of molecular events that ultimately impact endogenous metabolism. Qualitative and quantitative characterization of metabolomic profiles is a pragmatic approach to studying the risks of radiation exposure since it provides a phenotypic readout. Studies were conducted in irradiated nonhuman primates (NHP) to investigate metabolic changes in plasma and plasma-derived exosomes. Specifically, rhesus macaques (Macaca mulatta) were exposed to cobalt-60 gamma-radiation and plasma samples were collected prior to and after exposure to 5.8 Gy or 6.5 Gy radiation. Exosomes were isolated using ultracentrifugation and analyzed by untargeted profiling via ultra-performance liquid chromatography mass spectrometry (UPLC-MS) based metabolomic and lipidomic analyses, with the goal of identifying a molecular signature of irradiation. The enrichment of an exosomal fraction was confirmed using quantitative ELISA. Plasma profiling showed markers of dyslipidemia, inflammation and oxidative stress post-irradiation. Exosomal profiling, on the other hand, enabled detection and identification of low abundance metabolites that comprise exosomal cargo which would otherwise get obscured with plasma profiling. We discovered enrichment of different classes of metabolites including N-acyl-amino acids, Fatty Acid ester of Hydroxyl Fatty Acids (FAHFA&rsquo s), glycolipids and triglycerides as compared to the plasma metabolome composition with implications in mediation of systemic response to radiation induced stress signaling. |
Databáze: | OpenAIRE |
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