Role of CREB in the regulatory action of sarsasapogenin on muscarinic M1 receptor density during cell aging.
This work studied the role of cyclic AMP responsive element binding protein (CREB) in the up-regulation of M(1) muscarinic acetylcholine receptor (M(1) receptor) density by sarsasapogenin (ZMS) in CHO cells transfected with M(1) receptor gene (CHOm1 cells). During cell aging, sarsasapogenin elevated M(1) receptor density as well as CREB and phosphor-CREB (pCREB) levels. CREB peaked earliest, followed by pCREB and M(1) receptor density peaked last. When CREB synthesis was blocked by antisense oligonucleotides, the elevation effect of sarsasapogenin on M(1) receptor density was abolished. These results suggest that sarsasapogenin up-regulates M(1) receptor density in aged cells by promoting CREB production and phosphorylation. Furthermore, the results support the hypothesis that pCREB regulates M(1) receptor gene expression through heterodimer formation.
Hu
Haiyan
H
Research Laboratory of Cell Regulation, Shanghai Jiaotong University School of Medicine, Shanghai, China. hyx@shsmu.edu.cn
Zhang
Rui
R
Zhang
Yongfang
Y
Xia
Zongqin
Z
Hu
Yaer
Y
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D016922:Cellular Senescence / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D017362:Cyclic AMP Response Element-Binding Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D007700:Kinetics; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D013150:Spirostans / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D017362:Cyclic AMP Response Element-Binding Protein; D016376:Oligonucleotides, Antisense; D010750:Phosphoproteins; D043643:Receptor, Muscarinic M1; D013150:Spirostans; C046297:sarsasapogenin; D004121:Dimethyl Sulfoxide