1993 Fiscal Year Final Research Report Summary
Expression of the quinolinate-synthesizing enzyme gene in the brain of the epilepsy-prone El mice
| Project/Area Number |
03660080
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用生物化学・栄養化学
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| Research Institution | Nagoya University BioScience Center |
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Principal Investigator |
NAKANO Kiwao Nagoya Univ. BioScience Center, Assoc. prof., 生物分子応答研究センター, 助教授 (10023433)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Epilepsy / Quinolinic aid / El mouse |
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| Research Abstract |
Quinolinic acid (QUIN) is a structural analog of neurotransmitters, L-glutamate and L-aspartate and, hence, may act as an excitotoxin when it is abundant in the brain. The purpose of this study is to examine the possible involvement of QUIN in the pathogenesis of the epileptic diseases. It was found that the activity of 3-hydroxyanthranilate 3,4-dioxygenase (3-HAOase), a QUIN-synthesizing enzymes, was very high in the brain of the epilepsy-prone El mice. In contrast, there was no significant difference in the activity of the QUIN-degradating enzymes, QUIN-phophoribosystransferase, between the brain of the El mice and that of the control mice. The QUIN content in the cerebral cortex of the El mice was twice as high as that of the control mice. These results, in together, indicate that high concentration of QUIN in the brain of the epileptogenic mice may be due to abnormal expression of the gene for 3-HAOase. In order to estimate the mode of expression of the gene we then tried to clone its c-DNA.At first, 3-HAOase was purified from the rat liver to a single protein. Its N-terminal amino acids were then sequenced. The DNA oligonucleotides were synthesized in referring to the amino acid sequence. The c-DNA for the enzyme was cloned using the oligonucleotides as probes.
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