2003 Fiscal Year Final Research Report Summary
V-ATPase Inhibitor, pH and Cell Growth Inhibition
| Project/Area Number |
14370741
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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 | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
OHKUMA Shoji Kanazawa University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (10119563)
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| Co-Investigator(Kenkyū-buntansha) |
SOMEI Masanori Kanazawa University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20110546)
OHTA Tetsuo Kanazawa University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (40194170)
YOKOYAMA Ken Kanazawa University, JCST/ERATO Yoshida ATP system Project, Research Fellow, 吉田ATPシステムプロジェクト, 研究員 (70271377)
HATANAKA Yasumaru Toyama Medical Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30111181)
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| Project Period (FY) |
2002 – 2003
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| Keywords | V-ATPase / Bafilomycin / Concanamycin / Affinity Probe / Neurite OutGrowth / Apoptosis / Necrosis / Cell Growth |
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| Research Abstract |
Even in bafilomycin-resistant cells, lysosomal pH was increased by bafilomycins, ammonia or chloroquine, and prodigiosins indeced apoptosis. These cells were sensitive to concanamycins, suggesting the binding site(s) these componds are different from each other. Bafilomycins adn concanamacyns act on the cells from outside plasma membrane from theresults that membrane-impermeable concaamycins also induced neurite-outgrowth and apoptosis. Photoaffinity labelling suggested the presence of other protein(s) than 16kDa proteolipid subunit of V-ATPase.
Results with antisence-oligonucleotide against V-ATPase subunits suggested that Vo proteolipids but not V1 subunit inhibited the cell growth and induced cell death(necrosis). Similar inhibitin of cell growth was observed by antibodies against V-ATPase subunits. The cells are dead through apoptosis. These results are not affected by te presence of imidazole and ammonia, suggesting that cellular pH are not responsible to the effect of antisence oligonucleotide or antibody on cellular viability. The presence of receptor(s) for apoptosis on teh plasme membrenes.
We have isolated and determined the V-ATPase from the plasma membrane of Thermus thermophilis and suceeded in showing the rotation of V-ATPase.
We have looked into the new inhibitors against V-ATPase in nude mice, if these substances inhibited the growth of tumors.
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Research Products
(22 results)
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[Publications] Yokoyama, K., Fukumoto, K., Murakami, T., Harada, S., Hosono, R., Wadhwa, R., Mitsui, Y., Ohkuma, S.: "Extended longevity of C.elegans by knocking in extra copies of hsp70F, a homologue of mot-2(mortalin)/mthsp70/Grp75."FEBS Lett.. 516. 53-57 (2002)
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[Publications] Tanigaki, K., Sato, T., Tanaka, Y., Ochi, T., Nishikawa, A., Nagai, K., Kawashima, H., Ohkuma, S.: "BE-18 591 as a new H+/Cl-symport ionophore that inhibits immunoproliferation and gastritis."FEBS Lett.. 524. 37-42 (2002)
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[Publications] Yokoyama, K., Nagata, K., Imamura, H., Ohkuma, S., Yoshida, M., Tamakoshi, M.: "Subunit arrangement in V-ATPase from Thermusthermophilus."J.Biol.Chem.. 278. 42686-42691 (2003)
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[Publications] Kurisu, M., Morita, M., Kashiwayama, Y., Yokota, S., Hayashi, H., Sakai, Y., Ohkuma, S., Nishimura, M., Imanaka, T.: "Existence of catalase-less peroxisomes in Sf21 insect cells."Biochem.Biophys.Res.Commun.. 306. 169-176 (2003)
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[Publications] Zhan, H., Yokoyama, K., Otani, H., Tanigaki, K., Shirota, N., Takano, S., Ohkuma, S.: "Different roles of proteolipids and 70-kDasubunits of V-ATPase in growth and death of cultured human cells."Gene.Cell.. 8. 501-513 (2003)
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[Publications] Imamura, H., Nakano, M., Noji, H., Muneyuki, E., Ohkuma, S., Yoshida, M., Yokoyama, K.: "Evidence for rotation of V1-ATPase."Proc.Natl.Acad.Sci.USA.. 100. 2312-2315 (2003)
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「研究成果報告書概要(欧文)」より
