Contribution of Translin to Hematopoietic Regeneration after Sublethal Ionizing Irradiation

Abstract

The integrity of the genome is threatened by DNA damaging events such as radiation, viral infection and chemicals. Ionizing irradiation is known to cause genotoxic damage through the generation of reactive oxygen species (ROS) and nitrogen species (RNS) and we have found that a signaling pathway for the nuclear translocation of Translin is initiated in association and efficiently blocked by a specific inhibitor of nitric oxide synthase (NOS). This suggests the involvement of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) in the nuclear translocation of Translin. To address the functional significance of Translin in the hematopoietic generation system after ionizing irradiation, we generated Translin-deficient (Translin^−/−) mice and examined hematopoietic colony formation after sublethal ionizing irradiation. We thereby confirmed a severe delay of colony formation in the spleens of Translin^−/− as compared with Translin^+/+ mice. Taken together, the results suggest that Translin contributes to hematopoietic regeneration by acting as a sensor protein for radiation-induced damage.