Identification of Key Uric Acid Synthesis Pathway in a Unique Mutant Silkworm Bombyx mori Model of Parkinson's Disease

Hiroko Tabunoki, Hiromasa Ono, Hiroaki Ode, Kazuhiro Ishikawa, Natsuki Kawana, Yutaka Banno, Toru Shimada, Yuki Nakamura, Kimiko Yamamoto, Jun ichi Satoh, Hidemasa Bono

研究成果: ジャーナルへの寄稿記事

13 引用 (Scopus)

抄録

Plasma uric acid (UA) levels decrease following clinical progression and stage development of Parkinson's disease (PD). However, the molecular mechanisms underlying decreases in plasma UA levels remain unclear, and the potential to apply mutagenesis to a PD model has not previously been discovered. We identified a unique mutant of the silkworm Bombyx mori (B.mori) op. Initially, we investigated the causality of the phenotypic "op" by microarray analysis using our constructed KAIKO functional annotation pipeline. Consequently, we found a novel UA synthesis-modulating pathway, from DJ-1 to xanthine oxidase, and established methods for large-scale analysis of gene expression in B. mori. We found that the mRNA levels of genes in this pathway were significantly lower in B. mori op mutants, indicating that downstream events in the signal transduction cascade might be prevented. Additionally, levels of B.mori tyrosine hydroxylase (TH) and DJ-1 mRNA were significantly lower in the brain of B. mori op mutants. UA content was significantly lower in the B. mori op mutant tissues and hemolymph. The possibility that the B. mori op mutant might be due to loss of DJ-1 function was supported by the observed vulnerability to oxidative stress. These results suggest that UA synthesis, transport, elimination and accumulation are decreased by environmental oxidative stress in the B. mori op mutant. In the case of B. mori op mutants, the relatively low availability of UA appears to be due both to the oxidation of DJ-1 and to its expenditure to mitigate the effects of environmental oxidative stress. Our findings are expected to provide information needed to elucidate the molecular mechanism of decreased plasma UA levels in the clinical stage progression of PD.

元の言語英語
記事番号e69130
ジャーナルPloS one
8
発行部数7
DOI
出版物ステータス出版済み - 7 24 2013

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taxonomic keys
Bombyx
Parkinson disease
uric acid
Bombyx mori
silkworms
Uric Acid
Parkinson Disease
mutants
synthesis
Oxidative stress
Plasmas
oxidative stress
Oxidative Stress
tyrosine 3-monooxygenase
Signal transduction
Mutagenesis
Messenger RNA
Xanthine Oxidase
Tyrosine 3-Monooxygenase

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

これを引用

Identification of Key Uric Acid Synthesis Pathway in a Unique Mutant Silkworm Bombyx mori Model of Parkinson's Disease. / Tabunoki, Hiroko; Ono, Hiromasa; Ode, Hiroaki; Ishikawa, Kazuhiro; Kawana, Natsuki; Banno, Yutaka; Shimada, Toru; Nakamura, Yuki; Yamamoto, Kimiko; Satoh, Jun ichi; Bono, Hidemasa.

:: PloS one, 巻 8, 番号 7, e69130, 24.07.2013.

研究成果: ジャーナルへの寄稿記事

Tabunoki, H, Ono, H, Ode, H, Ishikawa, K, Kawana, N, Banno, Y, Shimada, T, Nakamura, Y, Yamamoto, K, Satoh, JI & Bono, H 2013, 'Identification of Key Uric Acid Synthesis Pathway in a Unique Mutant Silkworm Bombyx mori Model of Parkinson's Disease', PloS one, 巻. 8, 番号 7, e69130. https://doi.org/10.1371/journal.pone.0069130
Tabunoki, Hiroko ; Ono, Hiromasa ; Ode, Hiroaki ; Ishikawa, Kazuhiro ; Kawana, Natsuki ; Banno, Yutaka ; Shimada, Toru ; Nakamura, Yuki ; Yamamoto, Kimiko ; Satoh, Jun ichi ; Bono, Hidemasa. / Identification of Key Uric Acid Synthesis Pathway in a Unique Mutant Silkworm Bombyx mori Model of Parkinson's Disease. :: PloS one. 2013 ; 巻 8, 番号 7.
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AU - Banno, Yutaka

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