Hyung Joon Cho1, Won Hee Lee2, Olivia Min Ha Hwang3, William E Sonntag4, Yong Woo Lee3. 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.
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.
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