Contribution of Translin to hematopoietic regeneration after sublethal ionizing irradiation.
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.
Fukuda
Yuko
Y
Department of Immunology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
Ishida
Reiko
R
Aoki
Katsunori
K
Nakahara
Kazuhiko
K
Takashi
Tohru
T
Mochida
Keiji
K
Suzuki
Osamu
O
Matsuda
Junichiro
J
Kasai
Masataka
M
D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics / Q000502:physiology; D003600:Cytosol / Q000502:physiology; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D005720:Gamma Rays; D006413:Hematopoietic System / Q000502:physiology* / Q000528:radiation effects*; D006801:Humans; D015151:Immunoblotting; D020014:K562 Cells; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology; D016601:RNA-Binding Proteins; D012038:Regeneration / Q000502:physiology / Q000528:radiation effects
D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; C498303:Tsn protein, mouse