Senescence-associated secretory phenotype and activation of NF-κB in splenocytes of old mice exposed to irradiation at a young age. (September 2021)

• Record Type: Journal Article
• Authors: Song, Yuan; Okazaki, Ryuji; Yoshida, Yasuhiro
• Is Part Of: Developmental and comparative immunology. Volume 122(2021)
• Publication Date: 2021-09
• Subjects: Irradiation -- CDK2 -- NF-κB -- Senescence -- SASP -- Splenocyte; CDK Cyclin-dependent kinases -- Cdc6 Cell division cycle 6 -- EMSA Electrophoretic mobility shift assay -- SASP Senescence-associated secretory phenotype -- UOEH University of Occupational and Environmental Health; Immunology -- Periodicals; Developmental immunology -- Periodicals; 616.079
• DOI: 10.1016/j.dci.2021.104124
• Languages: English
• ISSNs: 0145-305X

Abstract

Abstract: 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 IKKα, NF-κB inhibitor alpha, and p65. Electrophoretic mobility shift assay demonstrated that active forms of NF-κB 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-κB-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. Graphical abstract: Image 1 Highlights: Irradiation enhanced the expression and phosphorylation of p53 and CDK2 at old age. LPS-induced IL-6 production was enhanced in mouse splenocytes irradiated at 8 weeks. ATP levels were also increased in splenocytes of mice irradiated at 8 weeks of age. Enhanced CDK2 expression was induced in CD45R/B220 + cells of irradiated mice. p65 phosphorylation was induced in CD45R/B220 + cells of irradiated mice.