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Plasma Derived Exosomal Biomarkers of Exposure to Ionizing Radiation in Nonhuman Primates
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274965/ https://www.ncbi.nlm.nih.gov/pubmed/30388807 http://dx.doi.org/10.3390/ijms19113427 |
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author | Cheema, Amrita K. Hinzman, Charles P. Mehta, Khyati Y. Hanlon, Briana K. Garcia, Melissa Fatanmi, Oluseyi O. Singh, Vijay K. |
author_facet | Cheema, Amrita K. Hinzman, Charles P. Mehta, Khyati Y. Hanlon, Briana K. Garcia, Melissa Fatanmi, Oluseyi O. Singh, Vijay K. |
author_sort | Cheema, Amrita K. |
collection | PubMed |
description | 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’s), glycolipids and triglycerides as compared to the plasma metabolome composition with implications in mediation of systemic response to radiation induced stress signaling. |
format | Online Article Text |
id | pubmed-6274965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62749652018-12-15 Plasma Derived Exosomal Biomarkers of Exposure to Ionizing Radiation in Nonhuman Primates Cheema, Amrita K. Hinzman, Charles P. Mehta, Khyati Y. Hanlon, Briana K. Garcia, Melissa Fatanmi, Oluseyi O. Singh, Vijay K. Int J Mol Sci Article 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’s), glycolipids and triglycerides as compared to the plasma metabolome composition with implications in mediation of systemic response to radiation induced stress signaling. MDPI 2018-11-01 /pmc/articles/PMC6274965/ /pubmed/30388807 http://dx.doi.org/10.3390/ijms19113427 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cheema, Amrita K. Hinzman, Charles P. Mehta, Khyati Y. Hanlon, Briana K. Garcia, Melissa Fatanmi, Oluseyi O. Singh, Vijay K. Plasma Derived Exosomal Biomarkers of Exposure to Ionizing Radiation in Nonhuman Primates |
title | Plasma Derived Exosomal Biomarkers of Exposure to Ionizing Radiation in Nonhuman Primates |
title_full | Plasma Derived Exosomal Biomarkers of Exposure to Ionizing Radiation in Nonhuman Primates |
title_fullStr | Plasma Derived Exosomal Biomarkers of Exposure to Ionizing Radiation in Nonhuman Primates |
title_full_unstemmed | Plasma Derived Exosomal Biomarkers of Exposure to Ionizing Radiation in Nonhuman Primates |
title_short | Plasma Derived Exosomal Biomarkers of Exposure to Ionizing Radiation in Nonhuman Primates |
title_sort | plasma derived exosomal biomarkers of exposure to ionizing radiation in nonhuman primates |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274965/ https://www.ncbi.nlm.nih.gov/pubmed/30388807 http://dx.doi.org/10.3390/ijms19113427 |
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