Journal article
Superoxide Mediates Acute Liver Injury in Irradiated Mice Lacking Sirtuin 3
Antioxidants & redox signaling, Vol.20(9), pp.1423-1435
03/20/2014
DOI: 10.1089/ars.2012.5091
PMCID: PMC3936509
PMID: 23919724
Abstract
Aims:
This study determined whether acute radiation-induced liver injury seen in Sirtuin3
−/−
mice after exposure to Cs-137 γ-rays was mediated by superoxide anion (O
2
•−
).
Results:
Male wild-type (WT) and SIRT3
−/−
mice were given 2×2 Gy whole-body radiation doses separated by 24 h and livers were harvested 20 h after the second dose.
Ex vivo
measurements in fresh frozen liver sections demonstrated 50% increases in dihydroethidium oxidation from SIRT3
−/−
animals, relative to WT animals, before irradiation, but this increase was not detected 20 h after radiation exposure. In addition, irradiated livers from SIRT3
−/−
animals showed significant hydropic degeneration, loss of MitoTracker Green FM staining, increased immunohistochemical staining for 3-nitrotyrosine, loss of Ki67 staining, and increased mitochondrial localization of p53. These parameters of radiation-induced injury were significantly attenuated by an intraperitoneal injection of 2 mg/kg of the highly specific superoxide dismutase mimic, GC4401, 30 min before each fraction.
Innovation:
Sirtuin 3 (SIRT3) is believed to regulate mitochondrial oxidative metabolism and antioxidant defenses in response to acute radiation-induced liver injury. This work provides strong evidence for the causal role of O
2
•−
in the liver injury process initiated by whole-body irradiation in SIRT3
−/−
mice.
Conclusion:
These results support the hypothesis that O
2
•−
mediates acute liver injury in SIRT3
−/−
animals exposed to whole-body γ-radiation and suggest that GC4401 could be used as a radio-protective compound
in vivo
.
Antioxid. Redox Signal.
20, 1423–1435.
Details
- Title: Subtitle
- Superoxide Mediates Acute Liver Injury in Irradiated Mice Lacking Sirtuin 3
- Creators
- Mitchell C Coleman - 1Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, Carver College of Medicine, The University of Iowa, Iowa City, IowaAlicia K Olivier - 2Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, IowaJames A Jacobus - 1Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, Carver College of Medicine, The University of Iowa, Iowa City, IowaKranti A Mapuskar - 1Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, Carver College of Medicine, The University of Iowa, Iowa City, IowaGaowei Mao - 1Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, Carver College of Medicine, The University of Iowa, Iowa City, IowaSean M Martin - 2Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, IowaDennis P Riley - 3Galera Therapeutics, St. Louis, MissouriDavid Gius - 4Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, IllinoisDouglas R Spitz - 1Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, Carver College of Medicine, The University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Antioxidants & redox signaling, Vol.20(9), pp.1423-1435
- DOI
- 10.1089/ars.2012.5091
- PMID
- 23919724
- PMCID
- PMC3936509
- NLM abbreviation
- Antioxid Redox Signal
- ISSN
- 1523-0864
- eISSN
- 1557-7716
- Publisher
- Mary Ann Liebert, Inc
- Language
- English
- Date published
- 03/20/2014
- Academic Unit
- Pathology; Orthopedics and Rehabilitation; Radiation Oncology
- Record Identifier
- 9984040004902771
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