2007 Fiscal Year Final Research Report Summary
A novel function of tryptophan key enzyme in the brain and its regulation mechanism
| Project/Area Number |
17580105
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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 | Chiba University |
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Principal Investigator |
EGASHIRA Yukari Chiba University, Faculty of Horticulture, Professor (80213528)
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| Co-Investigator(Kenkyū-buntansha) |
SANADA Hiroo Chiba University, Faculty of Horticulture, Professor (60196293)
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| Project Period (FY) |
2005 – 2007
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| Keywords | tryptophan / quinolinate / picolinate / ACMSD / rat |
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| Research Abstract |
α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) plays a key role in regulating NAD biosynthesis from tryptophan. ACMSD also seems to affect the generation of quinolinate from tryptophan. Qunolinate is a potent endogenous excitotoxin of neuronal cells. In this study, we examined the effect of food components, hormone or medicine on quinolinic acid production. When diets containing test materials were given to rats for 8 days, dietary plant oil, fish oil, high protein or peroxisome proliferators affected quinolinic acid production by suppressing ACMSD mRNA expression and activity. There was the negative correlation between the sum of liver and kidney ACMSD activities, and the quinolinic acid concentration. We also showed differential effects of pyrazinamide and peroxisome proliferators on gene expression of rat ACMSD. The transcription level of ACMSD is modulated by polyunsaturated fatty acid and peroxisome proliferators, and the fluctuation of the ACMSD expression was followed by that of the ACMSD activity. However pyrazinamide does not affect the transcription level of ACMSD. We also showed down-regulation of ACMSD by polyunsatu-rated fatty acids in hepatocytes is not mediated by peroxisome proliferator-activated receptor (PPAR) α. Next we examined the localization of ACMSD in the brain. Using in situ hybridization, localization ACMSD mRNA expressing hippocampus or cerebellum was observed.
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