Cui Chen1, Xin-yi Mu1, Yue Zhou2, Ke Shun1, Shan Geng1, Jun Liu1, Jian-wei Wang1, Jie Chen3, Tin-yu Li3, Ya-Ping Wang1. 1. Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. 2. Department of Histology and Embryology, Dali University, Dali 671000, China. 3. Chongqing Stem Cell Therapy Engineering Technical Center, Chongqing 400016, China.
Abstract
AIM: To investigate the effects of ginsenoside Rg1 on the radiation-induced aging of hematopoietic stem/progenitor cells (HSC/HPCs) in mice and the underlying mechanisms. METHODS: Male C57BL/6 mice were treated with ginsenoside Rg1 (20 mg·kg(-1)·d(-1), ip) or normal saline (NS) for 7 d, followed by exposure to 6.5 Gy X-ray total body irradiation. A sham-irradiated group was treated with NS but without irradiation. Sca-1(+) HSC/HPCs were isolated and purified from their bone marrow using MACS. DNA damage was detected on d 1. The changes of anti-oxidative activities, senescence-related markers senescence-associated β-galactosidase (SA-β-gal) and mixed colony-forming unit (CFU-mix), P16(INK4a) and P21(Cip1/Waf1) expression on d 7, and cell cycle were examined on d 1, d 3, and d 7. RESULTS: The irradiation caused dramatic reduction in the number of Sca-1(+) HSC/HPCs on d 1 and the number barely recovered until d 7 compared to the sham-irradiated group. The irradiation significantly decreased SOD activity, increased MDA contents and caused DNA damage in Sca-1(+) HSC/HPCs. Moreover, the irradiation significantly increased SA-β-gal staining, reduced CFU-mix forming, increased the expression of P16(INK4a) and P21(Cip1/Waf1) in the core positions of the cellular senescence signaling pathways and caused G1 phase arrest of Sca-1(+) HSC/HPCs. Administration of ginsenoside Rg1 caused small, but significant recovery in the number of Sca-1(+) HSC/HPCs on d 3 and d 7. Furthermore, ginsenoside Rg1 significantly attenuated all the irradiation-induced changes in Sca-1(+) HSC/HPCs, including oxidative stress reaction, DNA damage, senescence-related markers and cellular senescence signaling pathways and cell cycle, etc. CONCLUSION: Administration of ginsenoside Rg1 enhances the resistance of HSC/HPCs to ionizing radiation-induced senescence in mice by inhibiting the oxidative stress reaction, reducing DNA damage, and regulating the cell cycle.
AIM: To investigate the effects of ginsenosideRg1 on the radiation-induced aging of hematopoietic stem/progenitor cells (HSC/HPCs) in mice and the underlying mechanisms. METHODS: Male C57BL/6 mice were treated with ginsenosideRg1 (20 mg·kg(-1)·d(-1), ip) or normal saline (NS) for 7 d, followed by exposure to 6.5 Gy X-ray total body irradiation. A sham-irradiated group was treated with NS but without irradiation. Sca-1(+) HSC/HPCs were isolated and purified from their bone marrow using MACS. DNA damage was detected on d 1. The changes of anti-oxidative activities, senescence-related markers senescence-associated β-galactosidase (SA-β-gal) and mixed colony-forming unit (CFU-mix), P16(INK4a) and P21(Cip1/Waf1) expression on d 7, and cell cycle were examined on d 1, d 3, and d 7. RESULTS: The irradiation caused dramatic reduction in the number of Sca-1(+) HSC/HPCs on d 1 and the number barely recovered until d 7 compared to the sham-irradiated group. The irradiation significantly decreased SOD activity, increased MDA contents and caused DNA damage in Sca-1(+) HSC/HPCs. Moreover, the irradiation significantly increased SA-β-gal staining, reduced CFU-mix forming, increased the expression of P16(INK4a) and P21(Cip1/Waf1) in the core positions of the cellular senescence signaling pathways and caused G1 phase arrest of Sca-1(+) HSC/HPCs. Administration of ginsenosideRg1 caused small, but significant recovery in the number of Sca-1(+) HSC/HPCs on d 3 and d 7. Furthermore, ginsenosideRg1 significantly attenuated all the irradiation-induced changes in Sca-1(+) HSC/HPCs, including oxidative stress reaction, DNA damage, senescence-related markers and cellular senescence signaling pathways and cell cycle, etc. CONCLUSION: Administration of ginsenosideRg1 enhances the resistance of HSC/HPCs to ionizing radiation-induced senescence in mice by inhibiting the oxidative stress reaction, reducing DNA damage, and regulating the cell cycle.
Authors: G P Dimri; X Lee; G Basile; M Acosta; G Scott; C Roskelley; E E Medrano; M Linskens; I Rubelj; O Pereira-Smith Journal: Proc Natl Acad Sci U S A Date: 1995-09-26 Impact factor: 11.205
Authors: Marcella L Porto; Bianca P Rodrigues; Thiago N Menezes; Sara L Ceschim; Dulce E Casarini; Agata L Gava; Thiago Melo C Pereira; Elisardo C Vasquez; Bianca P Campagnaro; Silvana S Meyrelles Journal: J Biomed Sci Date: 2015-10-24 Impact factor: 8.410