Project/Area Number |
12670627
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | Osaka Medical College |
Principal Investigator |
FURUTAMA Daisuke Osaka Medical College Faculty of Medicine, Research Associate, 医学部, 助手 (70291987)
|
Co-Investigator(Kenkyū-buntansha) |
OHSAWA Nakaaki Aino Institute for Aging Research, President, 藍野加齢医学研究所, 所長
MATSUYAMA Kuniko (TSUJI Kuniko) 大阪医科大学, 医学部, 専攻医
FUJITA Atsushi Osaka Medical College Faculty of Medicine, Research Assistant, 医学部, 専攻医
松山 久仁子(辻) 大阪医科大学, 医学部, 専攻医
松山 久仁子(辻 久仁子) 大阪医科大学, 医学部, 専攻医
|
Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
Keywords | steroid / nuclear receptor / transcription factor / skeletal muscle / liver / myotonic dystrophy |
Research Abstract |
We investigated whether DHEA or DHEA-S affected the activities of nuclear receptors, with special reference to CARβ. Administration of DHEA or DHEA-S enhanced the DNA binding of hepatic nuclear extracts to responsive elements for the retinoic acid receptor (RARE), the retinoic acid receptor β2 (β RARE) and the peroxisome proliferator activated receptor (HD-PPRE). The bound complexes were shown to the CARβ-RXR heterodimer by antibody-supershift assays. The expression of a target gene of CARβ, Cyp2b10, was increased in liver by DHEA or DHEA-S treatment, suggesting that DHEA or DHEA-S actually activated CARβ in vivo. It was suggested that the metabolic conversion of DHEA, DHEA-S to CARβ ligands could occur in vivo and the metabolites could regulate the expression of CARβ target gene expression. Our results provide new insights into the in vivo relationship between DHEA/ DHEA-S and CARβ activation.
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