2002 Fiscal Year Final Research Report Summary
The transcriptional regulation of the human β1-adrenergic receptor gene by stress-related transcription molecules
| Project/Area Number |
12670961
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | St. Marianna University School of Medicine |
|---|
Principal Investigator |
MATSUI Hiroaki St. Marianna University School of Medicine, Department of Medicine, Professor, 医学部, 教授 (90181685)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ASAKURA Mikio St. Marianna University School of Medicine, Department of Medicine, Associate Professor, 医学部, 助教授 (70103504)
HIROI Tomoko St. Marianna University School of Medicine, Department of Medicine, Assistant Professor, 医学部, 助手 (20238398)
|
|---|
| Project Period (FY) |
2000 – 2002
|
| Keywords | β1-adrenergic receptor / NF-Y / AP-2 / CREB / Glucocorticoid receptor / Transcriptional repression / Antidepressant |
|---|
| Research Abstract |
We characterized the transcription factors involved in the regulation of the human β1-adrenergic receptor (β1-AR) gene expression and studied effects of stress-related transcription molecules, such as glucocorticoid receptor(GR) and heat shock factors, on the transcription of the β1-AR gene in human neuroblastoma SY5Y ceils. Deletional and mutational analyses of the β1-AR gene promoter-luciferase reporter gene constructs revealed that the trimeric transcription factor NF-Y binding site, located in -369/-365 relative to the translation start codon, has a pivotal role in the regulation of the β 1-AR gene expression. In addition, we found one potential binding site for CREB (-353/-346) and two sites for AP-2 (-345/-337 and -332/-324) near the NF-Y binding site. By introducing mutations into either of the two AP-2 sites, the β1-AR gene expression was moderately reduced. In contrast, CREB binding site mutation was less effective in the reduction of the β1-AR gene expression. These results indicate that NF-Y regulates the β1-AR gene expression by recruiting AP-2. Treatment with glucocorticoid (GC) inhibited the β1-AR gene expression in SY5Y cells. Assuming that GR Interacts with NF-Y through the protein-protein interaction, GC-mediated inhibition of the β1-AR gene expression can occur through the sequestration of NF-Y by GR from the β1-AR gene promoter.
|
Research Products
(11 results)
