我们的网站为什么显示成这样？

可能因为您的浏览器不支持样式，您可以更新您的浏览器到最新版本，以获取对此功能的支持，访问下面的网站，获取关于浏览器的信息：

|本期目录/Table of Contents|

白藜芦醇-Sirt1Foxo1调控通路对缺氧心肌细胞的保护作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2009年第1期
页码:
23-28
栏目:
基础研究
出版日期:
2009-02-28

文章信息/Info

Title:
Protective effect of resveratrol-Sirt1-Foxo1 pathway on anoxic cardiocytes
作者:
王伟1; 陈纯娟1; 傅玉才2; 王欣1; 余伟1
汕头大学医学院:1.第一附属医院心血管内科，2.细胞衰老实验室，广东 汕头 515041
Author(s):
WANG Wei1;  CHEN Chun-juan1;  FU Yu-cai2;  WANG Xin1;  YU Wei1
1.Department of Cardiology, First Hospital affiliated, 2.Laboratory of cell senesceng, Shantou University Medical College, Shantou 515041, Guangdong, China
关键词:
白藜芦醇; Sirt1; Foxo1; 心肌细胞; 凋亡
Keywords:
resveratrol;  sirt1;  foxo1;  cardiocyte;  apoptosis
分类号:
R541.4
DOI:
-
文献标识码:
A
摘要:
目的 研究白藜芦醇-Sirt1-Foxo1调控通路对缺氧心肌细胞的保护作用。方法 将大鼠心肌细胞株H9C2培养48 h后，随机分为5组，即20 μmol/L白藜芦醇(resveratrol,Res)干预组、二甲基亚砜（dimethyl sulfoxide,DMSO）对照组、40 mmol/L尼克酰胺（nicotinamide,Nam）干预组、Nam空白对照组及正常对照组。培养24 h后终止培养，用RT-PCR法和免疫细胞化学染色法检测Sirt1、Foxo1、p27、Bim mRNA及其蛋白表达水平的变化；用TUNEL法及流式细胞仪（flow cytometer，FCM）分析细胞凋亡和细胞周期。结果 20 μmol/L Res干预组可使Sirt1 mRNA及SIRT1蛋白表达的水平增加。Sirt1可通过抑制Foxo1 mRNA的转录活性而调节其下游基因p27及Bim的表达。SIRT1的高表达可使细胞周期延长，细胞凋亡减少。结论 Res干预可使SIRT1表达增加。Sirt1可能通过对Foxo1及其下游基因Bim、p27的调控，延长心肌细胞的细胞周期，减少其凋亡。
Abstract:
AIM To study the protective effect of resveratrol-Sirt1-Foxo1 pathway on anoxic cardiocytes. METHODS H9C2 embryonal rat heart-derived cells were randomly divided into five groups: 20 μmol/L resveratrol (Res) group, dimethyl sulfoxide (DMSO) group, 40 mmol/L nicotinamide (Nam) group, Nam control group and normal control group. After the 24-hour culture, the expressions of Sirt1, Foxo1, p27, Bim mRNA and their proteins were respectively detected using RT-RCR and the immunocytochemical staining. The apotosis and cell cycle of H9C2 cells were analyzed by TUNEL staining followed by flow cytometry(FCM). RESULTS The expression of Sirt1 mRNA and protein increased after incubation with 20 μmol/L resveratrol. Sirt1 regulated p27 and Bim by inhibiting the transcription activity of Foxo1. More cells were arrested at the G0+G1 checkpoint and cell apoptosis decreased after treatment with resveratrol. CONCLUSION Res promotes the expression of Sirt1 and Sirt1 protects the cardiomyocytes from hypoxia-induce apoptosis and promotes cell cycle arrest, which may be implemented by the regulation of Foxo1 and its downstream genes such as Bim and p27.

参考文献/References

[1］ Anekonda TS, Reddy PH. Nuronal protection by sirtuins in Alzheimer's disease［J］. Neurochemistry, 2006, 96(2):305-313.
［2］ Alcendor RR, Gao S, Zhai P, et al. Sirt1 regulates aging and resistance to oxidative stress in the heart［J］. Circ Res, 2007, 100(10): 1512-1521.
［3］ Brunet A, Sweeney LB, Sturgill JF, et al. Stressdependent regulation of FOXO transcription factors by the SIRT1 deacetylase［J］. Science, 2004, 303(5666):2011-2015.
［4］ Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol［J］. Biol Chem, 2005, 280(17):17187-17195.
［5］ Jang JH, Surh YJ. Protective effects of resveratrol on hydrogen peroxideinduced poptosis in rat pheochromocytoma (PC12) cells［J］. Mutation Res, 2001, 496(1-2):181-190.
［6］ 陈丽函,王伟,傅玉才,等.白藜芦醇对缺血再灌注心肌细胞凋亡及沉寂信息调节因子2表达的影响［J］. 中国临床康复, 2006, 10（19）:69-71.
［7］ Jonassen AK, Brar BK, Mjos OD, et al. Insulin administered at reoxygenation exerts a cardioprotective effect in myocytes by a possible antiapoptotic mechanism［J］. J Mol Cell Cardiol, 2000, 32(5):757-764.
［8］ Hisahara S, Chiba S, Matsumoto H, et al. Transcriptional regulation of neuronal genes and its effect on neural functions: NADdependent histone deacetylase SIRT1 (Sir2α) ［J］. Pharmacol Sci, 2005, 98(3):200-204.
［9］ Alcendor RR, Kirshenbaum LA, Imai S, et al. Silent information regulator 2, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes［J］. Circ Res, 2004, 95(10):971-980.
［10］Yoshida Y, Shioi T, Izumi T. Resveratrol ameliorates experimental autoimmune myocarditis［J］. Circulation, 2007, 71(3):397-404.
［11］Yang YH, Hou HY, Haller EM, et al. Suppression of FOXO1 activity by FHL2 through SIRT1mediated deacetylation［J］. EMBO J, 2005, 24(5):1021-1032.
［12］Friedman DB, Johnson TE. A mutation in the age1 gene in caenorhabditis elegans lengthens life and reduces hermaphrodite fertility［J］. Genetics, 1988, 118(1):75-86.
［13］Kenyon C. The plasticity of aging: insights from longlived mutants［J］. Cell, 2005, 120(4):449-460.
［14］Skurk C, Izumiya Y, Maatz H, et al. The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling［J］. Biol Chem, 2005, 28（21）:20814-20823.
［15］Wang Y, Tissenbaum HA. Overlapping and distinct functions for a caenorhabditis elegans SIR2 and DAF16/FOXO［J］. Mech Ageing Dev, 2006, 127(1):48-56.
［16］Schmidt MT, Smith BC, Jackson MD, et al. Coenzyme specificity of Sir2 protein deacetylases［J］. Biol Chem, 2004, 297 (38):40122-40129.
［17］Giannakou ME, Partridge L. The interaction between FOXO and SIRT1: tipping the balance towards survival［J］. Trends Cell Biol, 2004, 14（8）:408-412.
［18］Cunningham MA, Zhu Q, Hammod JM. FoxO1a can alter cell cycle progression by regulating the nuclear localization of p27kip in granulosa cells［J］. Mol Endocrinol, 2004, 18(7):1756-1767.

备注/Memo

备注/Memo:
收稿日期：2008-2-22.基金项目：广东省自然科学基金项目资助（5008363）；广东省 医学科研基金项目资助（B2006106） 作者简介：王伟，主任医师，硕士Email：janey_stu@163.com
更新日期/Last Update: 2009-04-02