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

研究成果査読

80 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)58-71
ページ数14
ジャーナルJournal of radiation research
53
1
DOI
出版ステータスPublished - 2012
外部発表はい

ASJC Scopus subject areas

  • 放射線
  • 放射線学、核医学およびイメージング
  • 健康、毒物学および変異誘発

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