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A novel function of tryptophan key enzyme in the brain and its regulation mechanism

脑内色氨酸关键酶的新功能及其调控机制

基本信息

批准号：
17580105
负责人：
EGASHIRA Yukari
金额：
$ 2.37万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17580105/
关键词：
tryptophan quinolinate picolinate ACMSD rat ナイアシンエイコサノイド

项目摘要

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.

α-氨基-β-羧基粘康酸-ε-半醛脱羧酶（ACMSD）在色氨酸生物合成NAD的过程中起着重要的调控作用。ACMSD似乎也影响色氨酸生成喹啉酸。喹诺酯是一种强的内源性神经元兴奋性毒素。在这项研究中，我们研究了食物成分，激素或药物对喹啉酸产生的影响。当给大鼠喂食含有试验材料的饲料8天时，饲料植物油、鱼油、高蛋白或过氧化物酶体增殖剂通过抑制ACMSD mRNA表达和活性影响喹啉酸的产生。肝、肾ACMSD活性之和与喹啉酸浓度呈负相关。我们还显示了吡嗪酰胺和过氧化物酶体增殖剂对大鼠ACMSD基因表达的不同影响。ACMSD的转录水平受多不饱和脂肪酸和过氧化物酶体增殖物的调节，ACMSD表达的波动跟随ACMSD活性的波动。而吡嗪酰胺对ACMSD的转录水平无影响。我们还发现多不饱和脂肪酸对ACMSD的下调作用不是由过氧化物酶体增殖物激活受体（PPAR）α介导的。接下来，我们研究了ACMSD在大脑中的定位。应用原位杂交技术观察ACMSD mRNA在海马和小脑的定位表达。