期刊
JOURNAL OF RADIATION RESEARCH
卷 53, 期 1, 页码 58-71出版社
OXFORD UNIV PRESS
DOI: 10.1269/jrr.11034
关键词
SOD2; Mitochondria; Radiation protection; Oxidative stress; 2 ',7 '-dichlorofluorescein; Regulation of gene expression; Pathway analysis
资金
- Ministry of Education, Culture, Sports and Technology of Japan [21510056]
- Global Center of Excellence Formation of a Strategic Base for Biodiversity and Evolutionary Research
- from Genome to Ecosystem [A06]
- Central Research Institute of Electric Power Industry (Tokyo)
- Nuclear Safety Research Enhancement Actions
- Grants-in-Aid for Scientific Research [24510064, 22390229, 21510056, 23390386, 24510071] Funding Source: KAKEN
Reactive oxygen species (ROS) act as a mediator of ionizing radiation-induced cellular damage. Previous studies have indicated that MnSOD (SOD2) plays a critical role in protection against ionizing radiation in mammalian cells. In this study, we constructed two types of stable He La cell lines overexpressing SOD2, He La S3/SOD2 and T-REx HeLa/SOD2, to elucidate the mechanisms underlying the protection against radiation by SOD2. SOD2 overexpression in mitochondria enhanced the survival of He La S3 and T-REx He La cells following gamma-irradiation. The levels of gamma H2AX significantly decreased in He La S3/SOD2 and T-REx HeLa/SOD2 cells compared with those in the control cells. MitoSox (TM) Red assays showed that both lines of SOD2-expressing cells showed suppression of the superoxide generation in mitochondria. Furthermore, flow cytometry with a fluorescent probe (2',7'-dichlorofluorescein) revealed that the cellular levels of ROS increased in He La S3 cells during post-irradiation incubation, but the increase was markedly attenuated in He La S3/SOD2 cells. DNA microarray analysis revealed that, of 47,000 probe sets analyzed, 117 and 166 probes showed more than 2-fold changes after 5.5 Gy of gamma-irradiation in control and HeLa S3/SOD2 cells, respectively. Pathway analysis revealed different expression profiles in irradiated control cells and irradiated SOD2-overexpressing cells. These results indicate that SOD2 protects HeLa cells against cellular effects of gamma-rays through suppressing oxidative stress in irradiated cells caused by ROS generated in the mitochondria and through regulating the expression of genes which play a critical role in protection against ionizing radiation.
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