期刊
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
卷 122, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.dci.2021.104124
关键词
Irradiation; CDK2; NF-kappa B; Senescence; SASP; Splenocyte
资金
- UOEH Research Grant for Advanced Research from the University of Occupational and Environmental Health, Japan [H231, 1301]
- Japan Society for the Promotion of Science [23510070, 20K21738]
- Grants-in-Aid for Scientific Research [20K21738, 23510070] Funding Source: KAKEN
The study revealed that mice exposed to radiation at a young age exhibited increased expression and phosphorylation of certain molecules in splenocytes, along with a NF-kappa B-related immune response and elevated levels of senescence marker proteins like CDKs and IL-6. This suggests that radiation-induced cellular senescence in the spleen involves DNA damage-related stress responses, potentially contributing to aging.
DNA damage-induced cellular senescence is involved in aging. We reported previously that p53(+/-) mice subjected to irradiation at a young age exhibited an increased number of splenic lymphocytes in the S and G2/M phases. However, the detailed nature of splenic disorders in these mice is not fully understood. In this study, we investigated the effects on molecules in splenocytes, especially on senescence factors after early exposure of mice to radiation. Mice, 8- (young) or 17-, 30-, and 41-week-old (old) p53(+/-) were subjected to 3-Gy whole-body irradiation. Splenocytes were prepared at 56 weeks of age. Immunoblot showed that irradiation at 8 weeks enhanced the expression and phosphorylation of p53, cyclin-dependent kinase 2, cell division cycle 6, and the MDM2 proto-oncogene in splenocytes. However, these molecules were not affected by irradiation at 17, 30, and 41 weeks of age. Similarly, irradiation at 8, but not 17, 30, or 41 weeks, induced phosphorylation of IKK alpha, NF-kappa B inhibitor alpha, and p65. Electrophoretic mobility shift assay demonstrated that active forms of NF-kappa B were increased. In addition, enzyme-linked immunosorbent assay showed that lipopolysaccharide-induced IL-6 production was enhanced in splenocytes of mice irradiated at 8 weeks. ATP levels were increased in splenocytes of mice irradiated at 8, but not 17, 30, or 41 weeks. CDK2 expression and p65 phosphorylation were induced in CD45R/B220(+) cells from irradiated mice. Overall, irradiation induced a NF-kappa B-related immune response in the spleen with an increase in senescence marker proteins, such as CDKs and IL-6, which are known to be typical senescence-associated secretory phenotype factors related to stresses, such as DNA damage.
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