Relief of superoxide dependent growth abnormality by ascorbic acid in chicken DT40 cells

Abstract

Superoxide dismutase (SOD) serves as the primary defense against superoxide. It has been shown that SOD1 is present in the cytoplasm, nucleus and mitochondrial intermembrane space and SOD2 is present in the mitochondrial matrix in vertebrate cells. Disruption of SOD1 or SOD2 results in cell death and growth delay, respectively in DT40 cells. Sister chromatid exchange frequency and the number of apurinic (AP) sites in chromosomes were increased in concomitant with SOD1 depletion. Neither such DNA damages nor mitochondrial dysfunction were not observed in SOD2 deficient cells. All the phenotypes involved the elevation of intracellular superoxide level in SOD1 depleted cells were completely suppressed by APM treatment. In addition to APM, either NAC or TIRON were able to rescue the growth delay in SOD2 depleted cells. These results suggest that SOD1 is essential for cell viability and playing a crucial role in the scavenging around cytoplasm and nucleus and preventing from DNA damage. And APM might scavenge the superoxide with offset the absence of the SOD1.