Mitochondrial Effects in the Liver of C57BL/6 Mice by Low Dose, High Energy, High Charge Irradiation

Galactic cosmic rays are primarily composed of protons (85%), helium (14%), and high charge/high energy ions (HZEs) such as <sup>56</sup>Fe, <sup>28</sup>Si, and <sup>16</sup>O. HZE exposure is a major risk factor for astronauts during deep-space travel due to the...

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Autores principales: Brooke L. Barnette, Yongjia Yu, Robert L. Ullrich, Mark R. Emmett
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:4236916339424d729201f822d8df4f3f2021-11-11T17:14:59ZMitochondrial Effects in the Liver of C57BL/6 Mice by Low Dose, High Energy, High Charge Irradiation10.3390/ijms2221118061422-00671661-6596https://doaj.org/article/4236916339424d729201f822d8df4f3f2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11806https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Galactic cosmic rays are primarily composed of protons (85%), helium (14%), and high charge/high energy ions (HZEs) such as <sup>56</sup>Fe, <sup>28</sup>Si, and <sup>16</sup>O. HZE exposure is a major risk factor for astronauts during deep-space travel due to the possibility of HZE-induced cancer. A systems biology integrated omics approach encompassing transcriptomics, proteomics, lipidomics, and functional biochemical assays was used to identify microenvironmental changes induced by HZE exposure. C57BL/6 mice were placed into six treatment groups and received the following irradiation treatments: 600 MeV/n <sup>56</sup>Fe (0.2 Gy), 1 GeV/n <sup>16</sup>O (0.2 Gy), 350 MeV/n <sup>28</sup>Si (0.2 Gy), <sup>137</sup>Cs (1.0 Gy) gamma rays, <sup>137</sup>Cs (3.0 Gy) gamma rays, and sham irradiation. Left liver lobes were collected at 30, 60, 120, 270, and 360 days post-irradiation. Analysis of transcriptomic and proteomic data utilizing ingenuity pathway analysis identified multiple pathways involved in mitochondrial function that were altered after HZE irradiation. Lipids also exhibited changes that were linked to mitochondrial function. Molecular assays for mitochondrial Complex I activity showed significant decreases in activity after HZE exposure. HZE-induced mitochondrial dysfunction suggests an increased risk for deep space travel. Microenvironmental and pathway analysis as performed in this research identified possible targets for countermeasures to mitigate risk.Brooke L. BarnetteYongjia YuRobert L. UllrichMark R. EmmettMDPI AGarticlespace radiationliversystems biologyintegrated omicsmitochondrial dysfunctionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11806, p 11806 (2021)
institution DOAJ
collection DOAJ
language EN
topic space radiation
liver
systems biology
integrated omics
mitochondrial dysfunction
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle space radiation
liver
systems biology
integrated omics
mitochondrial dysfunction
Biology (General)
QH301-705.5
Chemistry
QD1-999
Brooke L. Barnette
Yongjia Yu
Robert L. Ullrich
Mark R. Emmett
Mitochondrial Effects in the Liver of C57BL/6 Mice by Low Dose, High Energy, High Charge Irradiation
description Galactic cosmic rays are primarily composed of protons (85%), helium (14%), and high charge/high energy ions (HZEs) such as <sup>56</sup>Fe, <sup>28</sup>Si, and <sup>16</sup>O. HZE exposure is a major risk factor for astronauts during deep-space travel due to the possibility of HZE-induced cancer. A systems biology integrated omics approach encompassing transcriptomics, proteomics, lipidomics, and functional biochemical assays was used to identify microenvironmental changes induced by HZE exposure. C57BL/6 mice were placed into six treatment groups and received the following irradiation treatments: 600 MeV/n <sup>56</sup>Fe (0.2 Gy), 1 GeV/n <sup>16</sup>O (0.2 Gy), 350 MeV/n <sup>28</sup>Si (0.2 Gy), <sup>137</sup>Cs (1.0 Gy) gamma rays, <sup>137</sup>Cs (3.0 Gy) gamma rays, and sham irradiation. Left liver lobes were collected at 30, 60, 120, 270, and 360 days post-irradiation. Analysis of transcriptomic and proteomic data utilizing ingenuity pathway analysis identified multiple pathways involved in mitochondrial function that were altered after HZE irradiation. Lipids also exhibited changes that were linked to mitochondrial function. Molecular assays for mitochondrial Complex I activity showed significant decreases in activity after HZE exposure. HZE-induced mitochondrial dysfunction suggests an increased risk for deep space travel. Microenvironmental and pathway analysis as performed in this research identified possible targets for countermeasures to mitigate risk.
format article
author Brooke L. Barnette
Yongjia Yu
Robert L. Ullrich
Mark R. Emmett
author_facet Brooke L. Barnette
Yongjia Yu
Robert L. Ullrich
Mark R. Emmett
author_sort Brooke L. Barnette
title Mitochondrial Effects in the Liver of C57BL/6 Mice by Low Dose, High Energy, High Charge Irradiation
title_short Mitochondrial Effects in the Liver of C57BL/6 Mice by Low Dose, High Energy, High Charge Irradiation
title_full Mitochondrial Effects in the Liver of C57BL/6 Mice by Low Dose, High Energy, High Charge Irradiation
title_fullStr Mitochondrial Effects in the Liver of C57BL/6 Mice by Low Dose, High Energy, High Charge Irradiation
title_full_unstemmed Mitochondrial Effects in the Liver of C57BL/6 Mice by Low Dose, High Energy, High Charge Irradiation
title_sort mitochondrial effects in the liver of c57bl/6 mice by low dose, high energy, high charge irradiation
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/4236916339424d729201f822d8df4f3f
work_keys_str_mv AT brookelbarnette mitochondrialeffectsintheliverofc57bl6micebylowdosehighenergyhighchargeirradiation
AT yongjiayu mitochondrialeffectsintheliverofc57bl6micebylowdosehighenergyhighchargeirradiation
AT robertlullrich mitochondrialeffectsintheliverofc57bl6micebylowdosehighenergyhighchargeirradiation
AT markremmett mitochondrialeffectsintheliverofc57bl6micebylowdosehighenergyhighchargeirradiation
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