| Project/Area Number |
08680843
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
ABE Masako Medical Institute of Bioregulation Kyushu Univ.Research Associate, 生体防御医学研究所, 助手 (30222665)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Tomokazu Medical Institute of Bioregulation Kyushu Univ.Professor, 生体防御医学研究所, 教授 (20028517)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | N-ACETYLTRANFERASE / BRAIN / XENOBIOTICS / KYNURENINE / アリルアミンN-アセチルトランスフェラーゼ / アリルアミン / ニューロン |
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| Research Abstract |
Arylamine N-acetyltransferase (NAT) is mainly originated from liver that detoxify external arylamine. Brain derived NAT is rather high activity and has the possibility to detoxify external arylamine and endogenous arylamine analogues that might denature central nervous system. However the function of brain derived NAT is unknown. To clarify the function of brain derived NAT,we tried to find the distribution of NAT in ratbrain by in situ PCR.The signal from NAT mRNA was observed in both cytoplasm and nuclear of neuron. We could not determine whether the signal came from genomic DNA or not. Next we tried in situ hybridization in rat brain. Several kinds of antisence probes were chosen from comparative low homology region of monomorphic and polymorphic NAT cDNA.The signal from NAT mRNA was shown in neuron and ependymal cell layr. In the future we want to investigate the distribution of polymorphic NAT in the brain, in particular the region that is the gate from body fluid. Human polymorphic and monomorphic NAT were expressed in E.coli and were **rified in use of histidine tag. These enzymes were used to determine whether NAT playd any role in kynurenine pathway. Among of many candidates, we chose kynurenine and synthesized N'-acetyI-L-kynurenine as a standard. However NAT didn't metabolize kynurenine. Finally we investigated the effect of NAT on central nervous system. AIzheimer's disease is one of aging-related neurodegenerative disorders. We determined the typing of NAT2 (polymorphic) in AIzheimer's disease patient combined with normal people. They revealed that the distributions of NAT2 in AD patients were not significantly different from those observed in control subjects. However, they have suggested that rapid acetylator in the group of non-apolipoprotein E epsilon 4 carrier might be risk factors.
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