| Project/Area Number |
07672346
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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 | Faculty of Pharmaceutical Sciences, University of Tokyo |
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Principal Investigator |
ARAI Hiroyuki University of Tokyo, Faculty of Pharmaceutical Sciences, Associate Profesor, 薬学部, 助教授 (40167987)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Vitamine E / alpha-Tocopherol / alpha-Tocopherol transfer protein / Vitamine E deficiency / L-DL / Liver / 輸送蛋白質 / リポ蛋白質 / 輸送タンパク質 / 遺伝病 |
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| Research Abstract |
Alpha-tocopherol, the most biologcally active form of vitamin E,is a lipid soluble antioxidant that protects membranes from oxidative stresses. Vitamin E occurs in nature in eight different forms, but animal body is enriched in alpha-tocopherol compared with other forms. Studies on the transport vitamin E in animals and man suggest that the liver plays a key role in the preferential retention, and subsequent distribution of alpha-tocopherol to tissues, but little was known about the mechanism. Alpha-tocopherol transfer protein (alpha-TTP) is a cytosolic liver protein with highly specific binding ability for alpha-tocopherol. Alpha-TTP also has an ability to transport alpha-tocopherol between membranes in vitro. We have succeeded in purifying this protein from rat liver and isolating its cDNA from rat and human. Furthermore, we have demonstrated that the mutations in the gene that encodes alpha-TTP cause ataxia with familial vitamin E deficiecy. Patients with this disease have low or undetectable serum alpha-tocopherol concentrations and progressive spinocerebellar dysfunction. In these patients, the absorption of alpha-tocopherol from intestine and the transport to the liver is normal, but they have an impaired ability to incorporate alpha-tocopherol into VLDL in the liver. From these observation, it was found that alpha-TTP catalyze the transfer of alpha-tocopherol taken up by the liver into nascent VLDL.
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