机构：[1]Department of Medical Laboratory, Xuanwu Hospital of Capital Medical University, Beijing 100053, China首都医科大学宣武医院[2]Ageing Researching Center, Medical and Health Center of Peking University, Beijing 100083, China
Background Astragali Radix, the root of Astragalus 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 mu mol/L HDTIC-1 or 1.0 mu mol/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 mu mol/L HDTIC-1 or 1.0 mu mol/L HDTIC-2, there was a weak mRNA expression of p16 and no protein expression of p16 was observed. The expression level of p2l increased with cell ageing. Moreover, there was no difference between the expression level 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 mu mol/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 mu mol/L) or HDTIC-2 (10 mu mol/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 p16(INK4a)/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.
基金：
grants from the National Nature Science Foundation of China (No. 30672469) and Beijing Nature Science Foundation (No. 7062030).
第一作者机构：[1]Department of Medical Laboratory, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
通讯作者：
通讯机构：[1]Department of Medical Laboratory, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
推荐引用方式(GB/T 7714)：
WANG Pei-chang,ZHANG Zong-yu,ZHANG Jian,et al.Two isomers of HDTIC isolated from Astragali Radix decrease the expression of p16 in 2BS cells[J].CHINESE MEDICAL JOURNAL.2008,121(3):231-235.doi:10.1097/00029330-200802010-00009.
APA：
WANG Pei-chang,ZHANG Zong-yu,ZHANG Jian&TONG Tan-jun.(2008).Two isomers of HDTIC isolated from Astragali Radix decrease the expression of p16 in 2BS cells.CHINESE MEDICAL JOURNAL,121,(3)
MLA：
WANG Pei-chang,et al."Two isomers of HDTIC isolated from Astragali Radix decrease the expression of p16 in 2BS cells".CHINESE MEDICAL JOURNAL 121..3(2008):231-235
