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. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.