Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Cheema, Amrita K., Hinzman, Charles P., Mehta, Khyati Y., Hanlon, Briana K., Garcia, Melissa, Fatanmi, Oluseyi O., Singh, Vijay K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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
_version_ 1783377730305261568
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
work_keys_str_mv AT cheemaamritak plasmaderivedexosomalbiomarkersofexposuretoionizingradiationinnonhumanprimates
AT hinzmancharlesp plasmaderivedexosomalbiomarkersofexposuretoionizingradiationinnonhumanprimates
AT mehtakhyatiy plasmaderivedexosomalbiomarkersofexposuretoionizingradiationinnonhumanprimates
AT hanlonbrianak plasmaderivedexosomalbiomarkersofexposuretoionizingradiationinnonhumanprimates
AT garciamelissa plasmaderivedexosomalbiomarkersofexposuretoionizingradiationinnonhumanprimates
AT fatanmioluseyio plasmaderivedexosomalbiomarkersofexposuretoionizingradiationinnonhumanprimates
AT singhvijayk plasmaderivedexosomalbiomarkersofexposuretoionizingradiationinnonhumanprimates