| Project/Area Number |
12557088
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Endocrinology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TANAKA Hirotoshi The University of Tokyo, Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (00171794)
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| Co-Investigator(Kenkyū-buntansha) |
MAKINO Yuichi The University of Tokyo, Institute of Medical Science, JSPS fellow (PD), 医科学研究所, 日本学術振興会特別研究員
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2001: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2000: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | NUCLEAR RECEPTOR / TRANSCRIPTION FACTOR / MOLECULAR BIOLOGY / GENE EXPRESSION / PHARMACOLOGY / DRUG DEVELOPMENT / STEROID / ANTIINFLAMMATION / 炎症 / 創薬 / 免疫 |
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| Research Abstract |
Glucocorticoids perform these functions by binding to a cytoplasmic receptor protein glucocorticoid receptor (GR), which is a member of the nuclear receptor superfamily and acts as a ligand-inducible transcription factor. As a pharmaceutics, however, glucocorticoid therapy has two opposite faces : antiinflammation/immunosuppression and metabolic side effects. Pharmacological dissociation of these therapeutic effects and side effects have been a major concern. We have developed the screening strategy for isolation of selective GR modulator (SGRM) and found that at least two classes of compounds can dissociate GR-dependent gene expression. Notably, ursodeoxycholic (UDCA) acid could exploit desirable anti-NF-kB effect with little induction of transactivational function of the GR. Effect of UDCA appears to be specific for the GR, since either PR, AR, or MR could not be translocated into the nucleus in the presence of UDCA. On the other hand, redox drugs are another candidates of SGRM. Moreover, we have identified the region in the ligand binding domain that can convey selective modulation of the receptor function. These results could be a basis for further development of SGRM.
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