| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
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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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