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Two isomers of HDTIC isolated from Astragali Radix decrease the expression of p16 in 2BS cells

中华医学杂志(英文版)2008,Vol.121Issue(3):231-235,5.
中华医学杂志(英文版)2008,Vol.121Issue(3):231-235,5.

Two isomers of HDTIC isolated from Astragali Radix decrease the expression of p16 in 2BS cells

Two isomers of HDTIC isolated from Astragali Radix decrease the expression of p16 in 2BS cells

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作者信息

  • 1. Department of Medical Laboratory,Xuanwu Hospital of Capital Medical University,Beijing 100053,China;Ageing Researching Center,Medical and Health Center of Peking University,Beijing 100083,China;Department of Medical Laboratory,Xuanwu Hospital of Capital Medical University,Beijing 100053,China;Ageing Researching Center,Medical and Health Center of Peking University,Beijing 100083,China
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摘要

Abstract

Background Astragali Radix,the root of Aatragalus membranceus(Fish)Bunge Var.mongholicus(Bge),is a crude drug considered as one of the effective traditional Chinese anti-ageing material.The two isomers of 4-hydroxy-5-hydroxymethyl-[1,3]dioxolan-2,6'-spirane-5',6',7',8'-tetrahydro-indolizine-3,-carbaldehyde(HDTIC),HDTIC-1 and HDTIC-2.were first extracted from the herb in 2002.We demonstrated previously that 0.1 μmol/L HDTIC-1 or 1.0 μmol/L HDTIC-2 strongly delay replicative senescence of human fetal lung diploid fibroblasts(2BS).In this study,we chose them to investigate their effects on the expression of senescence-associated genes to explore the mechanism of how HDTIC delays replicative senescence.Methods The effects of HDTIC-1 and HDTIC.2 on the expression of p16 and p21 were observed in vitro by RT-PCR and Western blot.The anti-oxidative activities of the compounds were also observed by phenotype alteration after treatment with antioxidants.Results There was an obvious expression of p16 in the control senescent cells.However,in the 2BS cells,after 56 population doublings(PDs)grown from PD28 in 0.1 μmol/L HDTIC-1 or 1.0 μmol/L HDTIC-2,there was a weak mRNA expression of p16 and no protein expression of p16 was observed.The expression level of p21 increased with cell ageing.Moreover.there was no difference between the expression leveI of p21 in the control cells and that in the same PD cells cultured with HDTIC compounds.The results also showed that 2BS cells exposed to 100 μmol/L H2O2 for 5 minutes return to their non-senescent phenotype and continue to be confluent after incubating the damaged cells with HDTIC-1 (1.0 μmol/L)or HDTIC-2(10 μmol/L)for 1 hour.Conclusions Expression of p16 by 2BS cells was strongly Inhibited by HDTIC compounds,which could contribute to their delayed replicative senescence by the way of p16INK4a/Rb/MAPK.The anti-oxidative activities of HDTIC-1 and HDTIC-2,described in this study for the first time,might be indirectly related to their inhibition of p16 expression.

关键词

HDTIC/Astragali Radix/replicative senescence/fibroblast/gene expression

Key words

HDTIC/Astragali Radix/replicative senescence/fibroblast/gene expression

分类

医药卫生

引用本文复制引用

..Two isomers of HDTIC isolated from Astragali Radix decrease the expression of p16 in 2BS cells[J].中华医学杂志(英文版),2008,121(3):231-235,5.

基金项目

This work was supported by the grants from the National Nature Science Foundation of China(No.30672469)and Beijing Nature Science Foundation(No.7062030). (No.30672469)

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