RRC ID 27765
Author Tabunoki H, Ono H, Ode H, Ishikawa K, Kawana N, Banno Y, Shimada T, Nakamura Y, Yamamoto K, Satoh J, Bono H.
Title Identification of key uric acid synthesis pathway in a unique mutant silkworm Bombyx mori model of Parkinson's disease.
Journal PLoS One
Abstract 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.
Volume 8(7)
Pages e69130
Published 2013-1-1
DOI 10.1371/journal.pone.0069130
PII PONE-D-13-10045
PMID 23894418
PMC PMC3722175
MeSH Animals Bombyx Disease Models, Animal Mutation Oxidative Stress Parkinson Disease / genetics Parkinson Disease / metabolism* Signal Transduction / physiology Tyrosine 3-Monooxygenase / genetics Uric Acid / metabolism* Xanthine Oxidase / genetics
IF 2.74
Times Cited 18
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Silkworms o751