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  • Title: [Mechanism of hematopoietic stem/progenitor cell aging induced by radiation damage].
    Author: Zhang C, Sun K, Geng S, Liu D, Zhang X, Liu J, Xu C, Wang J, Wang Y.
    Journal: Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi; 2013 Mar; 29(3):233-6. PubMed ID: 23643076.
    Abstract:
    OBJECTIVE: To explore the mechanism underlying the aging of hematopoietic stem/progenitor cells (HSC/HPC) induced by radiation stress. METHODS: Male C57BL/6J mice were divided randomly into radiation group and control group. The radiation group were treated with total 6.5 Gy X-ray radiation for 24 h; the control group received the same treatment except radiation. Thereafter, Sca-1(+);HSC/HPC were isolated by magnetic-activated cell sorting (MACS) from bone marrow of all the mice. The distributions of cell cycle were tested by flow cytometry. The percentage of aging cells was detected by SA-β-Gal staining. The potentials of self-renewal and multi-differentiation were measured by CFU-Mix assay. DNA damages of Sca-1(+);HSC/HPC were analyzed by single cell gel electrophoresis technique (SCGE). The expressions of senescence-associated genes p16(INK4a);, p19(Arf);, p53, p21(Cip1/Waf1); mRNA were detected by RT-PCR. Western blotting was performed to analyze the expressions of p16(INK4a); and p21(Cip1/Waf1); proteins. RESULTS: The purity of Sca-1(+);HSC/HPC reached 94% after MACS. Compared with control group cells, after radiation, the number of Sca-1(+);HSC/HPC per femur and CFU-Mix sharply decreased (P<0.05), Sca-1(+);HSC/HPC apparently showed G1 arrest and elevated percentage of SA-β-Gal positive cells (P<0.05), cell trailing had a prolonged time, and the expressions of senescence-associated genes (p16(INK4a);, p19(Arf);, p53, p21(Cip1/Waf1);) and relevant proteins (p16(INK4a);, p21(Cip1/Waf1);) were up-regulated significantly (P<0.05). CONCLUSION: DNA damage and senescence-associated biological changes of Sca-1(+);HSC/HPC can be achieved by X-ray radiation, which may be involved in p16(INK4a);-Rb and p19(Arf);-p53-p21(Cip1/Waf1); signal pathways.
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