| Project/Area Number |
01580198
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
代謝生物化学
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
IWASHIMA Akio Kyoto Prefectural University of Medicine Department of Biochemistry, Professor, 医学部, 教授 (70079705)
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| Co-Investigator(Kenkyū-buntansha) |
NISHINO Hoyoku Kyoto Prefectural University of Medicine Department of Biochemistry, Associate P, 医学部, 助教授 (10079709)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Sugar Transport System / Hydrogen Peroxide / Superoxide / Na^+ / H^+ Exchanger / Tumor Promoter / Insulin / 2-Deoxyglucose / H^+交換体 / 2-デオキシグルコ-ス |
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| Research Abstract |
Xanthine/xanthine oxidase and H_2O_2 stimulated sugar transport in mouse fibroblasts. Application of superoxide dismutase and catalase to the cells showed an inhibitory effect on these agent-stimulated sugar transports. Addition of amiloride and 4-acetamide-4'isothiocyanostilbene-2, 2'-disulfonic acid(SITS), which abolish the cytoplasmic alkalinization, inhibited the stimulation of sugar transport by xanthine/xanthine oxidase in the presence of catalase. The calmodulin antagonists, N-(6-aminohexyl)-5-chloro1-naphthalenesulfonamide(W-7)and trifluoperazine inhibited H_2O_2 -stimulated sugar transport.
These results suggest that O^-_ stimulates sugar transport in an intracellular pH-dependent manner and that H_2O_2 stimulates sugar transport in a calcium-calmodulin-dependent manner. These mechanisms may be involved in sugar-transport stimulation in mouse fibroblast BALB/3T3 cells by the tumor-promoting phorbol ester phorbol-12, 13-dibutyrate and insulin, since the stimulatory effects of these agents were inhibited by scavengers of oxygen radicals.
Our previous studies showed that phorbol-12, 13-dibutyrate or insulin-stimulated sugar transport in mouse fibroblast Swiss 3T3 cells is regulated at least three different mechanisms ; i)calcium-calmodulin-dependent regulation, ii)intracellular ph-dependent regulation, and iii)calcium-activated phospholipid-dependent protein kinase-dependent regulation. These mechanisms lead to the translocation of sugar transporters from an intracellular sites to the plasma membrane ; this process results in an increase in the rate of sugar transport. Combining these previous observations with the present results, we have concluded that the calcium-calmodulin-dependent process in H_2O_2 -stimulated sugar transport system and intracellular ph-dependent process in O^-_ -stimulated sugar transport system may be involved in the essential steps for the stimulation of sugar transport in mouse fibroblast cells by phorbol-12, 13-dibutyrate and insulin.
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