REAL-TIME FLUORESCENCE IMAGING OF SIRT1 CYTOSOLIC TRANSLOCATION UNDER THE TREATMENT OF GROWTH FACTOR DEPRIVATION  

作　　者：CHENGBO MENG SHENGNAN WU DA XING 

机构地区：[1]Ministry of Education Key Laboratory of Laser Life Science and Institute of Laser Life Science,College of Biophotonics South China Normal University,Guangzhou 510631,China

出　　处：《Journal of Innovative Optical Health Sciences》2011年第2期133-141,共9页创新光学健康科学杂志（英文）

基　　金：The authors thank Prof.Yoshiyuki Horio for providing the plasmid SIRT1-EGFP.This research is supported by the National Basic Research Program of China(2010CB732602,2011CB910402);the Program for Changjiang Scholars and Innovative Research Team in University(IRT0829);the National Natural Science Foundation of China(30870676,30870658).

摘　　要：Sirtuins comprise a family of enzymes implicated in the determination of organismal lifespan in yeast and the nematode.Human sirtuin SIRT1 has been shown to deacetylate several proteins in a NADt-dependent manner.It is reported that SIRT1 regulates physiological processes including senescence,fat metabolism,glucose homeostasis,apoptosis,and neurodegeneration.In general,SIRT1 has initially been thought to represent an exclusive nuclear protein.However,depending on the cell lines and organisms examined,a partial or temporary cytoplasmic localization was observed in murine pancreatic beta cells and neonatal rat cardiomyocytes.Since SIRT1 deacetylates both histone and nonhistone-proteins,such as a number of transcription factors,changes in subcellular localization probably play a role in the regulation of its function.In the present studies,we investigated the subcellular localization of SIRT1 in response to growth factor deprivation in African green monkey SV40-transformed kidneyfibroblast cells(COS-7).Using SIRT1-EGFPfluorescence reporter,we found that SIRT1 localized to nucleus in physiological conditions.We devised a model enabling cell senescence via growth factor deprivation and found that SIRT1 partially translocated to cytosol under the treatment,suggesting a reduced level of SIRT1 activity.We found PI3K/Akt pathway was involved in the inhibition of SIRT1's cytosolic translocation,because inhibition of these kinases significantly decreased the amount of SIRT1 maintained in nucleus.Taken together,we demonstrate that growth factor deprivation induces cytosolic translocation of SIRT1,which suggests a possible connection between cytoplasm-localized SIRT1 and the aging process and provides a new application of single moleculefluorescence imaging of the molecule events in living cells.

关 键 词：Senescence growth factor starvation SIRT1 

分 类 号：R73[医药卫生—肿瘤]