TY - JOUR
T1 - Mitochondrial effects in the liver of c57bl/6 mice by low dose, high energy, high charge irradiation
AU - Barnette, Brooke L.
AU - Yu, Yongjia
AU - Ullrich, Robert
AU - Emmett, Mark
N1 - Funding Information:
This work was supported by the NASA Ground Based Studies in Space Radiobiology NNX15AD65G. This research was partially supported by a NASA/Texas Space Grant Consortium Fellowship (BLB), and a Shirley Patricia Parker & Katherina Siebert Award for Excellence in Oncologic Scholarship (BLB). We would like to acknowledge the Departments of Biochemistry and Molecular Biology and UTMB for additional support. The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan is a public interest foundation funded by the Japanese Min-istry of Health Labor and Welfare (MHLW) and the US Department of Energy (DOE). The research was also funded in part through DOE award DE-HS0000031 to the National Academy of Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Funding Information:
Funding: This work was supported by the NASA Ground Based Studies in Space Radiobiology NNX15AD65G. This research was partially supported by a NASA/Texas Space Grant Consortium Fellowship (BLB), and a Shirley Patricia Parker & Katherina Siebert Award for Excellence in Oncologic Scholarship (BLB). We would like to acknowledge the Departments of Biochemistry and Molecular Biology and UTMB for additional support. The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan is a public interest foundation funded by the Japanese Ministry of Health Labor and Welfare (MHLW) and the US Department of Energy (DOE). The research was also funded in part through DOE award DE-HS0000031 to the National Academy of Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Funding Information:
Acknowledgments: We would like to acknowledge William Russell Director of the UTMB Proteomics Core (the UTMB Mass Spectrometry Facility is supported in part by CPRIT grant no. RP190682 (W.K.R.) and Steven Widen Director of the UTMB Next Generation Sequencing Core for all their help and expertise with data acquisition for both the proteomics and transcriptomics and their willingness to always answer questions and provide feedback. We would like to acknowledge Alex Tan of Galveston Ball High School for all the work that she did on this project during her Bench Student Program in Emmett’s laboratory. We would also like to give special thanks to the NSRL Physicists, Michael Sivertz, Chiara La Tessa, I-Hung Chiang, and Adam Rusek; the NSRL Support, Angela Kim, Paula Bennett, James Jardine, Leah Selva, and Peter Guida; the BLAF Group: Debbie Snyder, Kerry Bonti, Corinne Baran, and MaryAnn Petry; and others at the BNL, for HZE beamline access and help with animal care and irradiations.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Galactic cosmic rays are primarily composed of protons (85%), helium (14%), and high charge/high energy ions (HZEs) such as56Fe,28Si, and16O. 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 Me V/n56Fe (0.2 Gy), 1 GeV/n16O (0.2 Gy), 350 MeV/n28Si (0.2 Gy),137Cs (1.0 Gy) gamma rays,137Cs (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.
AB - Galactic cosmic rays are primarily composed of protons (85%), helium (14%), and high charge/high energy ions (HZEs) such as56Fe,28Si, and16O. 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 Me V/n56Fe (0.2 Gy), 1 GeV/n16O (0.2 Gy), 350 MeV/n28Si (0.2 Gy),137Cs (1.0 Gy) gamma rays,137Cs (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.
KW - Integrated omics
KW - Liver
KW - Mitochondrial dysfunction
KW - Space radiation
KW - Systems biology
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U2 - 10.3390/ijms222111806
DO - 10.3390/ijms222111806
M3 - Article
C2 - 34769236
AN - SCOPUS:85118129771
SN - 1661-6596
VL - 22
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 21
M1 - 11806
ER -