2005 Fiscal Year Final Research Report Summary
Molecular mechanism of the novel oxidative stress in diabetes
| Project/Area Number |
16580109
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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 |
Food science
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| Research Institution | Meiji University |
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Principal Investigator |
TAKENAKA Asako Meiji University, Graduate School of Agriculture, Associate Professor, 農学部, 助教授 (40231401)
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| Project Period (FY) |
2004 – 2005
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| Keywords | α-tocopherol / vitamin E / α-TTP / insulin / lysosome / proteasome |
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| Research Abstract |
It has bee reported that a-tocopherol (vitamin E) concentration in blood was reduced in diabetic patients and animals that could induce another oxidative stress by reducing anti-oxidative activity. It has been established that liver has the main role to secrete food-derived a-tocopherol to circulation through function of a-tocopherol transfer protein (a-TTP) and a-TTP was a major determinant of plasma a-tocopherol level by this mechanism. We have found that hepatic a-TTP level was reduced in streptozotocin-induced diabetic rats and reduction of a-TTP concentration was also observed in hepatocytes cultured with low concentration of insulin (<10^<-10>M). Therefore, the aim of this study was to investigate the molecular mechanism of the reduction of hepatic a-TTP concentration under insulin depleted condition. Primary cultured rat hepatocyte was incubated with/without cyclohexymide (inhibitor of protein synthesis) and with various concentration of insulin for various periods and a-TTP level was measured by Western blot analysis. The results showed that a-TTP level decreased with low concentrations of insulin (10^<-10>M, 0M) while a-TTP level was not changed with high concentrations of insulin (10^<-8>M, 10^<-6>M) for 12 and 24 hours incubation. Furthermore, the decrease of a-TTP disappeared by preventing protein synthesis. Therefore, the decrease of a-TTP might be due to degradation by protease activity induced by low insulin concentration. Next, we investigated whether concentration of a-TTP were influenced by lysosome or proteasome inhibitor. The results showed that a-TTP concentration was greatly reduced by addition of lysosome inhibitors but not influened by a proteasome inhibitor. In conclusion, hepatic a-TTP may be degraded under low concentration of insulin, and a-TTP protease may be rapidly procecced by lysosome.
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Research Products
(2 results)
