2000 Fiscal Year Final Research Report Summary
Transcription factors insolved in the development of drug abuse and therapeutic drugs.
| Project/Area Number |
09357021
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Osaka University |
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Principal Investigator |
MIKI Naomasa Osaka Univ.Graduate Sch.of Med.Professor, 医学系研究科, 教授 (40094445)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGATA Kanato Tokyo Metropolitan Insti, for Neuroscince, Director, 研究部門長 (20263262)
TAIRA Eiichi Osaka Univ.Graduate Sch.of Med.Asoc.Prof., 医学系研究科, 助教授 (60263240)
KUO Che-hui Osaka Univ.Graduate Sch.of Med.Asoc.Prof., 医学系研究科, 助教授 (50126570)
OSUGI Takeshi Nihon Boehringer Ingelheim Co. group manager Scientist, 主席研究員 (50176880)
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| Project Period (FY) |
1997 – 2000
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| Keywords | morphine / Purα / gene expression / drug dependence / calcium / methamphetamine / methamphetamine-psychosis / Amida |
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| Research Abstract |
We have found that the activity of Purα, a single stranded DNA-binding protein, is changed with chronic morphine treatment. The DNA-binding activity was found to be enhanced by endogenous activator. The activator was purified and identified to be calmodulin (CaM) which enhanced the DNA-binding activity of Purα more than 10 times. CaMIII gene in three CaM genes was only activated by chronic morphine treatment. The enhancer activity of CRE/CREB and neurite outgrowth from PC12 cells were suppressed by Purα. These results suggest that Calcium signaling is involved in the gene expression by morphine.
Arc, an immediate early gene is reported to be induced markedly by methamphetamine in the brain. Amida was isolated by yeast two hybrid system. Amida has two nuclear translation signals and transported to the nuclei and caused cell death. Arc formed a complex with Amida and transported to nuclei and suppressed apoptotic activity of Amida. Amida was phosporylated at serine-180 by Cdc2/cyclin B and changed the DNA-binding activity. The data suggest that the ratio of Amida and Arc is a critical factor for cell death during methamphetamine administration, which may cause the methamphetamine psychosis.
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