The dynamic pattern of glucocorticoid receptor-mediated transcriptional responses in neuronal PC12 cells.
The aim of the current study was (i) to examine the overlap in the pattern of glucocorticoid receptor (GR)-mediated transcriptional responses between different neuronal substrates and (ii) to assess the nature of these responses by differentiating between primary and downstream GR-responsive genes. For this purpose, nerve growth factor-differentiated catecholaminergic PC12 cells were used in which endogenous GRs were activated briefly with a high dose of corticosterone followed by gene expression profiling 1 and 3 h afterwards using Affymetrix GeneChips. The results revealed a strikingly similar temporal pattern to that which was reported previously in hippocampus, with only down-regulated genes 1 h after GR activation and the majority of genes up-regulated 3 h after GR activation. Real-time quantatitive PCR of transcripts in cycloheximide-treated cells showed that all five GR-responsive genes selected from the 1-h time point were primary responsive, whereas all four GR-responsive genes selected from the 3-h time point were downstream responsive. At the level of individual genes, the overlap with the previously generated hippocampal data sets was small, illustrating the cell-type specifity of GR-mediated genomic responses. Finally, we identified a number of interesting genes, such as SWI/SNF, synaptosomal-associated protein 25 and certain Rab proteins which may play a role in the effects of glucocorticoids on catecholaminergic neuronal functioning.
Morsink
M C
MC
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Amsterdam, the Netherlands. maarten.morsink@gmail.com
Joëls
M
M
Sarabdjitsingh
R A
RA
Meijer
O C
OC
De Kloet
E R
ER
Datson
N A
NA
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000235:genetics
D002395:Catecholamines; D002868:Chromosomal Proteins, Non-Histone; D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; D011965:Receptors, Glucocorticoid; C445179:SWI-SNF-B chromatin-remodeling complex; D050825:Synaptosomal-Associated Protein 25; D014157:Transcription Factors; D003513:Cycloheximide; D020691:rab GTP-Binding Proteins; D003345:Corticosterone