Widnell K L, Chen J S, Iredale P A, Walker W H, Duman R S, Habener J F, Nestler E J
Laboratory of Molecular Psychiatry, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
J Neurochem. 1996 Apr;66(4):1770-3. doi: 10.1046/j.1471-4159.1996.66041770.x.
We have recently demonstrated that mRNA expression of cyclic AMP (cAMP) response element-binding protein (CREB) is down-regulated in CATH.a cells (a neural-derived cell line) by activation of the cAMP pathway. We now demonstrate that this down-regulation can be accounted for by a decrease in the rate of CREB gene transcription. It was found that cycloheximide, a protein synthesis inhibitor, prevented the forskolin-induced decrease in CREB mRNA levels in CATH.a cells. Nuclear run-on assays demonstrated that forskolin decreased the rate of CREB transcription by close to 50%. Moreover, forskolin decreased chloramphenicol acetyltransferase (CAT) activity in CATH.a cells transiently transfected with a construct containing 1,240 bp of CREB promoter fused to a CAT reporter plasmid. Possible mechanisms by which activation of the cAMP pathway leads to a decrease in CREB gene transcription are discussed.
我们最近证明，通过激活环磷酸腺苷（cAMP）途径，CATH.a细胞（一种神经源性细胞系）中环磷酸腺苷反应元件结合蛋白（CREB）的mRNA表达会下调。我们现在证明，这种下调可以通过CREB基因转录速率的降低来解释。研究发现，蛋白质合成抑制剂环己酰亚胺可阻止福斯高林诱导的CATH.a细胞中CREB mRNA水平的降低。核转录分析表明，福斯高林使CREB转录速率降低了近50%。此外，福斯高林降低了用含有与氯霉素乙酰转移酶（CAT）报告质粒融合的1240 bp CREB启动子构建体瞬时转染的CATH.a细胞中的氯霉素乙酰转移酶（CAT）活性。文中讨论了cAMP途径激活导致CREB基因转录减少的可能机制。
