Mitochondrial-Targeted Human Catalase Affords Neuroprotection From Proton Irradiation

Significant past work has linked radiation exposure of the CNS to elevated levels of oxidative stress and inflammation. These secondary reactive processes are both dynamic and persistent and are believed to compromise the functionality of the CNS, in part, by disrupting endogenous neurogenesis in th...

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Bibliographic Details
Published in:Radiation research 2013-07, Vol.180 (1), p.1-6
Main Authors: Liao, Alicia C., Craver, Brianna M., Tseng, Bertrand P., Tran, Katherine K., Parihar, Vipan K., Acharya, Munjal M., Limoli, Charles L.
Format: Article
Language:English
Subjects:
Animals
Catalase
Catalase - genetics
Catalase - metabolism
Cell Proliferation - radiation effects
Central Nervous System - growth & development
Central Nervous System - radiation effects
Gene Expression - genetics
Hippocampus
Hippocampus - growth & development
Hippocampus - radiation effects
Humans
Irradiation
Mice
Mice, Transgenic
Mitochondria
Mitochondria - metabolism
Mitochondria - radiation effects
Neurogenesis
Neurogenesis - radiation effects
Neuroprotective Agents - metabolism
Oxidative Stress
Proton irradiation
Protons
Radiation dosage
Reactive Oxygen Species - metabolism
REGULAR ARTICLES
Space life sciences
Standardized tests
Stem Cells - metabolism
Stem Cells - radiation effects
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Summary:Significant past work has linked radiation exposure of the CNS to elevated levels of oxidative stress and inflammation. These secondary reactive processes are both dynamic and persistent and are believed to compromise the functionality of the CNS, in part, by disrupting endogenous neurogenesis in the hippocampus. While evidence has shown neurogenesis to be sensitive to irradiation and redox state, the mechanistic basis underlying these effects is incompletely understood. To clarify the role of reactive oxygen species (ROS) in mediating radiation-induced changes in neurogenesis we have analyzed transgenic mice that overexpress human catalase localized to the mitochondria. With this model, we investigated the consequences of low dose and clinically relevant proton irradiation on neurogenesis, and how that process is modified in response to genetic disruption of mitochondrial ROS levels. In unirradiated animals, basal neurogenesis was improved significantly by reductions in mitochondrial ROS. In animals subjected to proton exposure, hippocampal progenitor cell proliferation was attenuated significantly by overexpression of human catalase in the mitochondria. Furthermore, expression of the MCAT transgene significantly improved neurogenesis in WT animals after low-dose proton exposure (0.5 Gy), with similar trends observed at higher dose (2 Gy). Our report documents for the first time the impact of proton irradiation on hippocampal neurogenesis, and the neuroprotective properties of reducing mitochondrial ROS through the targeted overexpression of catalase. © 2013 by Radiation Research Society
ISSN:0033-7587
1938-5404
DOI:10.1667/RR3339.1