2007 Fiscal Year Final Research Report Summary
Enhancing effects of vitamin C-regeneration gene and vitamin C recycling on prevention of cell death
| Project/Area Number |
17590064
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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 | Prefectural University of Hiroshima |
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Principal Investigator |
MIWA Nobuhiko Prefectural University of Hiroshima, Faculty of Life and Environmental Sciences, Professor (00142141)
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| Co-Investigator(Kenkyū-buntansha) |
SAITOH Yasukazu Prefectural University of Hiroshima, Faculty of Life and Environmental Sciences, Associate Lecturer (90405514)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Vitamin C regeneration / dhar Gene / Reactive oxygen species / Hydroperoxide / Cell death defense / Hydrogen-dissolved water |
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| Research Abstract |
1. In Chinese hamster ovary cells CHO that were transfected with a dehydroascorbic acid (DehAsc) reductase (dhar) gene-incorporated pRcCMV vector, DHAR proteins were expressed scarcely in the nuclei and distributed all over the cytoplasm where DHAR was absent for dhar-nontransfected cells, and the peroxylipid-induced cell mortality and DNA strand cleavages were demonstrated to be prevented by simultaneous administration with DehAsc and the glutathione derivative GSH-iPr. 2. In the post-ischemic reperfusion model, hypoxia and subsequent reoxygenation (H/R) system, cell mortality was markedly occurred for dhar-nontransfected cells, and prevented for dhar-transfected cells by DehAsc and GSH-iPr which were simultaneously administered at 2-5 hr before hypoxia treatment. 3. Simultaneous DehAsc/ GSH-iPr administration to CHO/dhar cells achieved, at 1-6 hr after the administration, enrichment of intracellular Asc, which markedly repressed intracellular hydroperoxides and hydrogen peroxides tha
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t increased either after the peroxylipid t-BuOOH treatment or drastically at 1-3 min after post-hypoxic reoxygenation with DehAsc/GSH-iPr. 4. Why have a dhar gene been evolutionarily conserved whereas the Asc-synthesis rate-determining enzyme gene GLO was omitted at a stage of the primates during biological evolution? In hydrogen-dissolved water with reducing properties such as a dissolved-hydrogen concentration of 963 ppb and a redox potential of -788 mV, Asc-recycling and intracellular uptake of DehAsc were not promoted in correspondence to diminished ROS (reactive oxygen species) amounts in CHO/dhar cells, and intracellular ROS was appreciably alleviated, in contrast to abundant ROS for hydrogen-deficient pure water-prepared culture media. Residual rates of Asc at 27 hr after aqueous dissolution were diminished to 20-30% versus the initial concentration for pure water, and retained over 70% for hydrogen-dissolved water. Thus a reductive environment like hydrogen-dissolved water decreased a need for dhar gene expression resulting in Asc regeneration, and consequently achieved so-called "gene saving" as purposiveness. In summary, evolutionary conservation of dhar gene in contrast to omission of GLO gene might be attributed to no realization for retention of reducing conditions such as hydrogen-dissolved water for 3.8 billion years of biology evolution, and efficient Asc-regeneration and ROS-repression were not satisfied by endogenous dhar gene, and necessitated transfer of exogenous dhar gene as shown in the present study. Less
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Research Products
(29 results)
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[Journal Article] Effects of ethyl-esterization, chain-lengths, unsaturation degrees, and hyperthennia on carcinostatic effect of omega-hydroxylated fatty acids2007
Author(s)
Kusumoto K, Kageyama K, Matsuda T, Takanori T, Tomura, Tanaka H, Yazama F, Miwa, N
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Journal Title
Exptl Oncol(Reviewed) Vol. 29
Pages: 106-110
Description
「研究成果報告書概要(欧文)」より
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