| Project/Area Number |
04452302
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Hokkaido University |
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Principal Investigator |
KAMO Naoki Hokkaido University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (10001976)
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| Co-Investigator(Kenkyū-buntansha) |
NARA Toshifumi Hokkaido University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (30241350)
MIYAUCHI Seiji Hokkaido University, Faculty of Pharmaceutical Sciences, lecturer, 薬学部, 講師 (30202352)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1992: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | Multi-drug resistance / P-glycoprotein / Haloferax volcanii / Anti-cancer reagents / Phodamine 123 / Fructose / Glucose / グルコース / 抗ガン剤 / Escherichia coli / Enterococcus hirae / Corynebacterium glutamicum / 抗ガン剤排出タンパク / P-glycoprotein(Pgp) / Ca-拮抗剤 / 高度好塩菌 / フルクトース / プロベネシド |
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| Research Abstract |
1.P-glycoprotein-like transporter in highly halophilic bacterium, Haloferax volcanii. P-glycoprotein (P-gp) is a ATP-driven transporter for many structually-unrelated hydrophobic cations such as anti-cancer reagents and dyes. We have isolated an mutant which can grow even in a medium containing high concentrations of anti-cancer reagents and showed that the resistance is due to an ATP-driven P-gp-like efflux pump. When the wild strain (whose efflux activity is small) was cultured in the presence of excess glucose, the efflux activity increased appreciably. No increase was observed using non-metabolizing sugars. The increase was also observed when cultured in the presence of various amino acids.
2. Fructose transport in Haloferax volcanii. We showed that the fructose is taken up by H.volcanii, whose driving force is Na^+-electrochemical potential difference. Previously, we also reported that glucose transport in this bacterium is a symport with Na^+. These Na^+-symport systems for glucose and fructose are the first report for bacterial cells.
3.Multi-drug resistance in E.coli, Enterococcus hirae and corynebacterium glutamicum. On the basis of this research, we have succeeded in isolating mutants of these bacteria which shows multi-drug resistance due to efflux pump. Characterization of these pumps may be an interesting and fruitfull further investigation.
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