Metabolic profiling of 3-nitropropionic acid early-stage Huntington's disease rat model using gas chromatography time-of-flight mass spectrometry
| Autor: | Eric Chun Yong Chan, Kai Lun Chang, Edward R. Browne, Chiu Cheong Aw, Catherine W. Goh, Lee Sun New, Mainak Mal |
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| Rok vydání: | 2011 |
| Předmět: |
medicine.disease_cause
Mass spectrometry Biochemistry Gas Chromatography-Mass Spectrometry Rats Sprague-Dawley Huntington's disease Galantamine medicine Animals Metabolomics Nootropic Agents chemistry.chemical_classification Electron Transport Complex II Neurodegeneration Brain General Chemistry medicine.disease Nitro Compounds Phenotype Mitochondria Rats Disease Models Animal Oxidative Stress Enzyme Huntington Disease chemistry Metabolome Time-of-flight mass spectrometry Propionates Oxidative stress medicine.drug |
| Zdroj: | Journal of proteome research. 10(4) |
| ISSN: | 1535-3907 |
| Popis: | 3-Nitropropionic acid (3-NP), a potent irreversible inhibitor of mitochondrial complex II enzyme, leads to mitochondrial dysfunction and oxidative stress in Huntington's disease (HD) rat model. In this study, biochemical assays were used to demonstrate the presence of oxidative stress and mitochondrial dysfunction in 3-NP early stage HD rat models. Gas chromatography time-of-flight mass spectrometry (GC/TOFMS) was applied to analyze metabolites in brain and plasma of 3-NP-treated and vehicle-dosed rats. The orthogonal partial least-squares discriminant analysis (OPLS-DA) model generated using brain metabolic profiles robustly differentiated the 3-NP early stage HD rat model from the control. Metabonomic characterization of the 3-NP HD rat model facilitated the detection of biomarkers that define the physiopathological phenotype of early stage HD and elucidated the treatment effect of galantamine. Brain marker metabolites that were identified based on the OPLS-DA model were associated with altered glutathione metabolism, oxidative stress, and impaired energy metabolism. The treatment effect of galantamine in early stage HD could not be concluded mechanistically using the brain metabotype. Our study confirmed that GC/TOFMS is a strategic and complementary platform for the metabonomic characterization of 3-NP induced neurotoxicity in the early stage HD rat model. |
| Databáze: | OpenAIRE |
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