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Int J Radiat Biol. 2017 Nov;93(11):1257-1266. doi: 10.1080/09553002.2017.1377360.

Role of NADPH oxidase in radiation-induced pro-oxidative and pro-inflammatory pathways in mouse brain.

Author information

1
a Department of Biochemistry and Molecular Biology , University of Miami Miller School of Medicine , Miami , FL , USA.
2
b Stanford Cardiovascular Institute , Stanford University , Stanford , CA , USA.
3
c Department of Biomedical Engineering and Mechanics , Virginia Tech , Blacksburg , VA , USA.
4
d Department of Geriatric Medicine , University of Oklahoma Health Sciences Center , Oklahoma City , OK , USA.

Abstract

PURPOSE:

The present study was designed to investigate our hypothesis that NADPH oxidase plays a role in radiation-induced pro-oxidative and pro-inflammatory environments in the brain.

MATERIALS AND METHODS:

C57BL/6 mice received either fractionated whole brain irradiation or sham-irradiation. The mRNA expression levels of pro-inflammatory mediators, such as TNF-α and MCP-1, were determined by quantitative real-time RT-PCR. The protein expression levels of TNF-α, MCP-1, NOX-2 and Iba1 were detected by immunofluorescence staining. The levels of ROS were visualized by in situ DHE fluorescence staining.

RESULTS:

A significant up-regulation of mRNA and protein expression levels of TNF-α and MCP-1 was observed in irradiated mouse brains. Additionally, immunofluorescence staining of Iba1 showed a marked increase of microglial activation in mouse brain after irradiation. Moreover, in situ DHE fluorescence staining revealed that fractionated whole brain irradiation significantly increased production of ROS. Furthermore, a significant increase in immunoreactivity of NOX-2 was detected in mouse brain after irradiation. On the contrary, an enhanced ROS generation in mouse brain after irradiation was markedly attenuated in the presence of NOX inhibitors or NOX-2 neutralizing antibody.

CONCLUSIONS:

These results suggest that NOX-2 may play a role in fractionated whole brain irradiation-induced pro-oxidative and pro-inflammatory pathways in mouse brain.

KEYWORDS:

Fractionated whole brain irradiation; NOX-2; ROS; inflammation

PMID:
28880721
PMCID:
PMC6080279
DOI:
10.1080/09553002.2017.1377360
[Indexed for MEDLINE]
Free PMC Article

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