Effects of sirtuin 6/nuclear factorκB signaling pathway in delaying hematopoietic stem cell and progenitor cell senescence with ginsenoside R1 during serial transplantation

doi:10.16098/j.issn.0529-1356.2015.05.008

Abstract

Abstract:

Objective To investigate the effect of sirtuin(SIRT)6/nuclear factor(NF)-κB signaling pathway in delaying hematopoietic stem cell (HSC) and progenitor cell(HPC) senescence with ginsenoside Rg1 during serial transplantation. Methods Sca-1⁺HSC/HPC from male donator mouse was isolated and purified by magnetic activated cell sorting (MACS). Sca-1⁺HSC/HPC replicability aged modelin vivo was established through the Sca-1⁺HSC/HPC serial transplantation. The femal recipient mice radiated lethal dose from 60Co γ ray were divided into four groups: the control group, the aged model group, the Rg1 treat aged group and the Rg1 prevent aged group. The effect of Rg1 to delay Sca-1⁺HSC/HPC senencence in vivo was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining, mixed hematopoietic progenitor cell culture and cell cycle assay. The expressions of SIRT6 and NF-κB mRNA and protein were detected by quantitative PCR and Western blotting. Results With the increasing of transplantation, Sca-1⁺HSC/HPC appeared aging characters. The number of cells entered G₀/G₁ phase and the percentage of SA-β-gal positive cells was increased, and the number of CFU-Mix was decreased. Compared with the aged model group, the number of cells entered G0/G1 phase and the percentage of SA-β-gal positive cells were decreased, the number of CFU-Mix was increased to Sca-1⁺ HSC/HPC in Rg1 treat aged group and Rg1 prevent aged group, the expression of SIRT6 mRNA and protein was up regulated and the expression of NF-κB mRNA and protein was down regulated in Rg1 treat aged group and Rg1 prevent aged group.The changes of Rg1 prevent aged group was significantly higher than Rg1 treat aged group. Conclusion Rg1 could resist Sca-1⁺HSC/HPC senescence during serial transplantation in which the signaling pathway of SIRT6-NF-κB may play an important role.

Key words:

Ginsenoside Rg1, Sirtuin6, Nuclear factor-κB, Sca-1+ HSC/HPC, Senescence, Real\, time PCR, Western blotting, Mouse

ZHOU Yue* WANG Ya-ping WANG Jian-wei DING Ji-chao. Effects of sirtuin 6/nuclear factorκB signaling pathway in delaying hematopoietic stem cell and progenitor cell senescence with ginsenoside R1 during serial transplantation[J]. AAS, 2015, 46(5): 623-628.

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