Mitochondria-targeted superoxide dismutase (SOD2) regulates radiation resistance and radiation stress responsein hela cells

Ayaka Hosoki, Shin Ichiro Yonekura, Qing Li Zhao, Zheng Li Wei, Ichiro Takasaki, Yoshiaki Tabuchi, Li Li Wang, Shiga Hasuike, Takaharu Nomura, Akira Tachibana, Kazunari Hashiguchi, Shuji Yonei, Takashi Kondo, Qiu Mei Zhang-Akiyama

Research output: Contribution to journalArticle

61 Citations (Scopus)

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. MitoSoxTM 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.

Original languageEnglish
Pages (from-to)58-71
Number of pages14
JournalJournal of radiation research
Volume53
Issue number1
DOIs
Publication statusPublished - Mar 12 2012
Externally publishedYes

ASJC Scopus subject areas

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

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  • Cite this

    Hosoki, A., Yonekura, S. I., Zhao, Q. L., Wei, Z. L., Takasaki, I., Tabuchi, Y., Wang, L. L., Hasuike, S., Nomura, T., Tachibana, A., Hashiguchi, K., Yonei, S., Kondo, T., & Zhang-Akiyama, Q. M. (2012). Mitochondria-targeted superoxide dismutase (SOD2) regulates radiation resistance and radiation stress responsein hela cells. Journal of radiation research, 53(1), 58-71. https://doi.org/10.1269/jrr.11034