| Project/Area Number |
10672057
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
TSUCHIYA Seishi School of Pharmacy, Professor, 薬学部, 教授 (90057323)
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| Co-Investigator(Kenkyū-buntansha) |
TERAMOTO Kenichi Graduate school, Tokyo Medical and Dental University, associate Professor, 大学院, 助教授 (80197813)
SAKAMOTO Takatoshi School of Pharmacy, assistant, 薬学部, 助手 (60287464)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | nitric oxide / inducible nitric oxide synthase / antisense oligonucleotide / phosphorothioate type / ischemic injury / Kupffer cell / DNA durg / ホスフォロチオエート型 / RAW264,7 |
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| Research Abstract |
The objective of this project was clarified whether antisense oligonucleotide (ODN) designed for inducible nitric oxide synthase (i-NOS) could suppress NO production in rat liver after ischemia and reperfusion injury, and the following findings were obtained.
1. Five kinds of phosphorothioate type antisense ODNs were designed from estimated 2nd structure of rat i-NOS mRNA.
2. NO production from parenchymal cells (PC) was inhibited by antisense ODN designed for rat and mouse i-NOS mRNA, and the sequence non-specific inhibition was also observed. NO production from non-parenchymal cells (NPC) was effectively inhibited by rat antisense ODN designed to 3'-untranslated region of mouse i-NOS mRNA.Low levels of NO production, however, were detected from control experiments, PC and NPC, so that we could not identify the effective antisense ODN sequences against rat i-NOS mRNA.
3. After ischemia and reperfusion injury, the time course of NO production from PC and NPC were estimated. A high NO production and induction of i-NOS mRNA were detected from rat liver of 30 min ischemia and 3 hr reperfusion.
Studies were currently underway to clarify whether antisense ODNs designed for i-NOS mRNA could suppress NO production following ischemia and reperfusion injury of rat liver.
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