| Project/Area Number |
10557221
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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 |
Biological pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
OHKUMA Shoji Pharmaceutical Sciences, Kanazawa University Professor, 薬学部, 教授 (10119563)
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| Co-Investigator(Kenkyū-buntansha) |
SOMEI Masanori Pharmaceutical Sciences, Kanazawa University Professor, 薬学部, 教授 (20110546)
YOKOYAMA Ken Pharmaceutical Sciences, Kanazawa University Assistance, 薬学部, 助手 (70271377)
ARAI Kunizo Pharmaceutical Sciences, Kanazawa University Assistant Professor, 薬学部, 講師 (50126562)
HATANAKA Yasumaru Toyama Medical Phamaseutical University, Pharmaceutical Sciences, Professor, 薬学部, 教授 (30111181)
OHTA Tetsuo Pharmaceutical Sciences, Kanazawa University Associate Professor, 医学部・附属病院, 助教授 (09671290)
永井 和夫 東京工業大学, 生命理工学部, 教授 (00011974)
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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 |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | bafilomycins / V-ATPase / PC12 / apoptosis / nurite outgrowth (NOG) / prodigiosins / cell-differentiation / concanamycins / 突起伸展 / デストラキシン |
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| Research Abstract |
In this project, we have investigated the mechanism of incuction of neurite outgrowth (NOG), cell differentiation, growth inhibiton and apoptosis by inhibitors against V-ATPases, such as bafilomycin, concanamycins and prodigiosins, and the mechanism of proton transport in V-ATPases.
We found that (1) V-ATPase inhibitors like bafilomycin induced apoptosis and NOG in new RNA-, protein-syntheses, and serine/threonine kinase-dependent mannaer, and K-252a- or A-kinase-independent manner, but they are different from each other : apoptosis-induction is different from NOG-induction in its insensitivitiy in tyrosin-phosphatase, arachidonate-cascade or Calmodulin-kinase independent manner, (2) apoptosis and NOG are also induced by prodigiosins but they are not induced by its H^+/Cl^- symporting activities, and (3) apoptosis or NOG is not induced by pH-differences between inside and outside of cells, because they are not induced by NH_4Cl, (4) We have succeeded in the synsesis of concanamycin A-photoaffinity probes active in V-ATPase-inhibition. (5) Prodigiosins are H^+/Cl^- symporters that uncoupled ATPases like F-, V-, P-ATPase and electron transport activity, in which prodigiosins inhibited proton-transport but no ATP hydrolysis (or electron transport) activiteis. Prodigiosins also strongly and reversibly uncoupled (H^+/K^+) ATPase-dependent proton-translocation from hog gastric mucosa. (6) We have succeeded in the cloning, proton-pump dependent ATP synthesis, and determation of operon structure of V-ATPase from a eubacterium (Thermus termophilus).
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