Elucidation of the role of DJ-1 for the uric acid synthesis pathway in the silkworm Bombyx mori
Project/Area Number |
26450465
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Insect science
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Research Institution | Tokyo University of Agriculture and Technology |
Principal Investigator |
Hiroko Tabunoki 東京農工大学, (連合)農学研究科(研究院), 講師 (80434190)
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Co-Investigator(Kenkyū-buntansha) |
坊農 秀雅 大学共同利用機関法人情報・システム研究機構(機構本部施設等), 統合データベースセンター, 准教授 (20364789)
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Co-Investigator(Renkei-kenkyūsha) |
YOKOYAMA Takeshi 東京農工大学, 大学院農学研究院, 准教授 (20210635)
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Research Collaborator |
Ito Katsuhiko
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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Keywords | パーキンソン病 / DJ-1 / 尿酸 / カイコガ / miRNA / 個体機能低下 / 尿酸合成 / RNA干渉 / RNA-seq / 酸化ストレス / 定量RT-PCR / B.mori / 変異体 / ポジショナルクローニング |
Outline of Final Research Achievements |
Plasma uric acid (UA) levels decrease following clinical progression of Parkinson’s disease (PD). This observation indicates that UA is utilized as the alternative anti-oxidative system when disruption of anti-oxidative system. However, the molecular mechanisms underlying decreases in plasma UA levels remain unclear. We found novel uric acid synthesis pathway in the B.mori mutant using Microarray analysis. Also, the mRNA level of xanthine dehydrogenase (BmXDH) was significantly decreased by RNA interference of Bombyx mori DJ-1 (BmDJ-1), indicating that BmDJ-1 would be controlled function of BmXDH. BmDJ-1 is homolog of human PD causative gene PARK-7 and, BmXDH is key enzyme in uric acid synthesis pathway. Additionally, a bioinformatics analysis was showed the target sequence of our discovered miRNA might be bind to BmDJ-1. Our findings are expected to elucidate the molecular mechanism of decreased plasma UA levels in the clinical stage progression of PD.
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Academic Significance and Societal Importance of the Research Achievements |
カイコの幼虫は皮膚に尿酸を蓄積するため、白く見える。日本には皮膚が"白くない"カイコ変異体が存在し、尿酸とパーキンソン病の関係を解析できる唯一の動物モデル生物である。カイコを用いて尿酸とパーキンソン病原因遺伝子DJ-1の関係を解析したところ、これらはお互いを制御する関係にあることを見出した。このように本研究は尿酸合成の基本的な分子メカニズムの理解に貢献できた。 日本国内では460万人ものパーキンソン病を含む神経変性疾患患者が推定されている。このため、新規予防法や治療薬開発に対する社会的要請は非常に高い。尿酸がパーキンソン病態進行の鍵を握ることが分かれば、治療法の開発にも貢献できると思われる。
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Report
(4 results)
Research Products
(50 results)
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[Journal Article] Identification of functional enolase genes of the silkworm Bombyx mori from public databases with a combination of dry and wet bench processes.2017
Author(s)
Kikuchi A, Nakazato T, Ito K, Nojima Y, Yokoyama T, Iwabuchi K, Bono H, Toyoda A, Fujiyama A, Sato R, Tabunoki H.
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Journal Title
BMC Genomics.
Volume: 18(1)
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Mapping and recombination analysis of two moth colour mutations, Black moth and Wild wing spot, in the silkworm Bombyx mori.2016
Author(s)
Ito K, Katsuma S, Kuwazaki S, Jouraku A, Fujimoto T, Sahara K, Yasukochi Y, Yamamoto K, Tabunoki H, Yokoyama T, Kadono-Okuda K, Shimada T.
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Journal Title
Heredity (Edinb).
Volume: 116(1)
Pages: 52-59
Related Report
Peer Reviewed / Open Access
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[Journal Article] Expression of the fructose receptor BmGr9 and its involvement in the promotion of feeding, suggested by its co-expression with neuropeptide F1 in Bombyx mori.2016
Author(s)
Mang D, Shu M, Tanaka S, Nagata S, Takada T, Endo H, Kikuta S, Tabunoki H, Iwabuchi K, Sato R.
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Journal Title
Insect Biochem Mol Biol.
Volume: 75
Pages: 58-69
Related Report
Peer Reviewed
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[Journal Article] Superoxide Dismutases, SOD1 and SOD2, Play a Distinct Role in the Fat Body during Pupation in Silkworm Bombyx mori.2015
Author(s)
Nojima Y, Ito K, Ono H, Nakazato T, Bono H, Yokoyama T, Sato R, Suetsugu Y, Nakamura Y, Yamamoto K, Satoh J, Tabunoki H, Fugo H.
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Journal Title
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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