Effect of SIRT6/NF-kappa B signal axis during hematopoietic stem and progenitor cell senescence induced by tert-butylhydroperoxide in vitro

doi:10.3969/j.issn.2095-4344.2014.37.011

Abstract

Abstract:

BACKGROUND: SIRT6/NF-κB is the important signal axis to cell senescence, but the effect of SIRT6/NF-κB signal axis to hematopoietic stem and progenitor cell (HSC/HPC) senescence is unclear.
OBJECTIVE: To induce (t-BHP) in vitro and to investigate the role of SIRT6/NF-κB signal axis in Sca-1⁺ HSC/HPC senescence induced by tert-butylhydroperoxide in vitro.
METHODS: Sca-1⁺HSC/HPC was isolated and purified by magnetic activated cell sorting. Sca-1⁺ HSC/HPC senescence was induced by 100 μmol/L tert-butylhydroperoxide in vitro. The senescence-associated β-Galactosidase staining, cell cycle analysis and culture of mixed hematopoietic progenitor cell were used to investigate the biological effects of tert-butylhydroperoxide on Sca-1⁺ HSC/HPC senescence. The expression of senescence associated SIRT6, NF-κB mRNA and protein was examined by real-time fluorescence quantitative PCR and western blot assay.
RESULTS AND CONCLUSION: Compared with control group, the percentage of positive cells expressing SA-β-Gal and cells in G0/G1 phase increased and the number of forming colony of mixed hematopoietic progenitor decreased in the aging group. It showed lower expression of SIRT6 and higher expression of NF-κB in the aging group. The SIRT6/NF-κB signal axis may play a key role in the Sca-1⁺ HSC /HPC senescence inducted by tert-butylhydroperoxide.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

全文链接：

Key words: hematopoietic stem cells, tert-butylhydroperoxide, aging, NF-kappa B

CLC Number:

R394.2

Zhou Yue, Wang Ya-ping, Wang Jian-wei, Ding Ji-chao, Yang Yong-qin . Effect of SIRT6/NF-kappa B signal axis during hematopoietic stem and progenitor cell senescence induced by tert-butylhydroperoxide in vitro[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(37): 5967-5971.

Figures/Tables 2

References

[1] Bee PC, Gan GG, Sangkar VJ,et al.Quality of life after haematopoietic stem cell transplantation in a multiracial population.Med J Malaysia. 2011;66(5):451-455.
[2] Raghavachari N.Gene Expression Profiling of Hematopoietic Stem Cells (HSCs).Methods Mol Biol. 2014; 1185:91-119.
[3] Hine C, Mitchell JR.Saying no to drugs: fasting protects hematopoietic stem cells from chemotherapy and aging.Cell Stem Cell. 2014;14(6):704-705.
[4] Schwer B, Schumacher B, Lombard DB,et al.Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity. Proc Natl Acad Sci U S A. 2010;107(50):21790-21794.
[5] Giblin W, Skinner ME, Lombard DB.Sirtuins: guardians of mammalian healthspan.Trends Genet. 2014;30(7):271-286.
[6] Parenti MD, Grozio A, Bauer I,et al.Discovery of novel and selective SIRT6 inhibitors.J Med Chem. 2014;57(11):4796- 4804.
[7] Zhou Y, Yang B, Yao X,et al.Establishment of an aging model of Sca-1+ hematopoietic stem cell and studies on its relative biological mechanisms.In Vitro Cell Dev Biol Anim. 2011;47(2): 149-156.
[8] Qin YS, Bu DX, Cui YY,et al.Difference in glycerol levels between leukemia and normal bone marrow stem cells.Oncol Lett. 2014;8(1):169-174.
[9] Smith AJ, Lewis FC, Aquila I,et al. Isolation and characterization of resident endogenous c-Kit+ cardiac stem cells from the adult mouse and rat heart.Nat Protoc. 2014; 9(7):1662-1681.
[10] Dykstra B, de Haan G.Hematopoietic stem cell aging and self-renewal.Cell Tissue Res. 2008;331(1):91-101.
[11] Valli H, Sukhwani M, Dovey SL,et al.Fluorescence- and magnetic-activated cell sorting strategies to isolate and enrich human spermatogonial stem cells.Fertil Steril. 2014;102(2): 566-580.
[12] Wang J, Sun Q, Morita Y, et al. A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage.Cell. 2012;148(5):1001-1014.
[13] Odendahl M, Grigoleit GU, Bönig H,et al.Clinical-scale isolation of 'minimally manipulated' cytomegalovirus-specific donor lymphocytes for the treatment of refractory cytomegalovirus disease.Cytotherapy. 2014;16(9):1245-1256.
[14] Chen SS, Chiorazzi N.Murine genetically engineered and human xenograft models of chronic lymphocytic leukemia. Semin Hematol. 2014;51(3):188-205.
[15] Rossi DJ, Bryder D, Weissman IL.Hematopoietic stem cell aging: mechanism and consequence.Exp Gerontol. 2007; 42(5):385-390.
[16] Gazit R, Weissman IL, Rossi DJ.Hematopoietic stem cells and the aging hematopoietic system.Semin Hematol. 2008; 45(4):218-224.
[17] Goodrich AD, Varain NM, Jeanblanc CM,et al.Influence of a dual-injection regimen, plerixafor and CXCR4 on in utero hematopoietic stem cell transplantation and engraftment with use of the sheep model.Cytotherapy. 2014;16(9):1280-1293.
[18] Kambham N, Higgins JP, Sundram U, et al.Hematopoietic stem cell transplantation: graft versus host disease and pathology of gastrointestinal tract, liver, and lung.Adv Anat Pathol. 2014;21(5):301-320.
[19] Tennen RI, Chua KF.Chromatin regulation and genome maintenance by mammalian SIRT6.Trends Biochem Sci. 2011;36(1):39-46.
[20] Tennen RI, Berber E, Chua KF. Functional dissection of SIRT6: identification of domains that regulate histone deacetylase activity and chromatin localization.Mech Ageing Dev. 2010;131(3):185-192.
[21] Li Y, Ohms SJ, Sun C,et al.NF-κB controls Il2 and Csf2 expression during T cell development and activation process. Mol Biol Rep. 2013;40(2):1685-1692.
[22] Yu SS, Cai Y, Ye JT,et al.Sirtuin 6 protects cardiomyocytes from hypertrophy in vitro via inhibition of NF-κB-dependent transcriptional activity.Br J Pharmacol. 2013;168(1):117-128.
[23] Jia G, Su L, Singhal S,et al.Emerging roles of SIRT6 on telomere maintenance, DNA repair, metabolism and mammalian aging.Mol Cell Biochem. 2012;364(1-2):345-350.
[24] Baohua Y, Li L.Effects of SIRT6 silencing on collagen metabolism in human dermal fibroblasts.Cell Biol Int. 2012; 36(1):105-108.
[25] Kawahara TL, Michishita E, Adler AS,et al.SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span.Cell. 2009;136(1):62-74.
[26] Ashburner BP, Westerheide SD, Baldwin AS Jr.The p65 (RelA) subunit of NF-kappaB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression.Mol Cell Biol. 2001;21(20):7065- 7077.
[27] Wan F, Lenardo MJ.The nuclear signaling of NF-kappaB: current knowledge, new insights, and future perspectives.Cell Res. 2010;20(1):24-33.
[28] Salminen A, Kaarniranta K.NF-kappaB signaling in the aging process.J Clin Immunol. 2009;29(4):397-405.
[29] Natoli G.When sirtuins and NF-kappaB collide.Cell. 2009; 136(1):19-21.
[30] Gertler AA, Cohen HY.SIRT6, a protein with many faces. Biogerontology. 2013;14(6):629-639.
[31] Etchegaray JP, Zhong L, Mostoslavsky R.The histone deacetylase SIRT6: at the crossroads between epigenetics, metabolism and disease.Curr Top Med Chem. 2013;13(23): 2991-3000.
[32] Ren Y, Shan TZ, Zhu LN,et al.Effect of breed on the expression of Sirtuins (Sirt1-7) and antioxidant capacity in porcine brain.Animal. 2013;7(12):1994-1998.
[33] Lee OH, Kim J, Kim JM,et al.Decreased expression of sirtuin 6 is associated with release of high mobility group box-1 after cerebral ischemia.Biochem Biophys Res Commun. 2013;438(2):388-394.