PMID:22302046

Citation	Hosoki, A, Yonekura, S, Zhao, QL, Wei, ZL, Takasaki, I, Tabuchi, Y, Wang, LL, Hasuike, S, Nomura, T, Tachibana, A, Hashiguchi, K, Yonei, S, Kondo, T and Zhang-Akiyama, QM (2012) Mitochondria-targeted superoxide dismutase (SOD2) regulates radiation resistance and radiation stress response in HeLa cells. J. Radiat. Res. 53:58-71
Abstract	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 HeLa cell lines overexpressing SOD2, HeLa 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 HeLa S3 and T-REx HeLa cells following γ-irradiation. The levels of γH2AX significantly decreased in HeLa 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 HeLa S3 cells during post-irradiation incubation, but the increase was markedly attenuated in HeLa 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 γ-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 γ-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.
Links	PubMed
Keywords	DNA Breaks, Double-Stranded; Enzyme Induction; Gamma Rays/adverse effects; Gene Expression Regulation/radiation effects; Gene Regulatory Networks/radiation effects; HeLa Cells/metabolism; HeLa Cells/radiation effects; Humans; Mitochondria/metabolism; Neoplasm Proteins/physiology; Oligonucleotide Array Sequence Analysis; Oxidative Stress/physiology; Oxidative Stress/radiation effects; Radiation Tolerance/genetics; Radiation Tolerance/physiology; Reactive Oxygen Species/metabolism; Recombinant Fusion Proteins/physiology; Superoxide Dismutase/biosynthesis; Superoxide Dismutase/genetics; Superoxide Dismutase/physiology; Superoxides/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:SODM		GO:0010212: response to ionizing radiation	ECO:0000315:		P		Reactive oxygen species harm the cell. SOD2 moderates this destruction. See Figure 3 & Table 1.	complete CACAO 3844

References

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