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

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.