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Title: Metabolic profiling of 3-nitropropionic acid early-stage huntingtons disease rat model using gas chromatography time-of-flight mass spectrometry
Authors: Chang, K.L.
New, L.S. 
Mal, M.
Goh, C.W.
Aw, C.C.
Browne, E.R.
Chan, E.C.Y. 
Keywords: 3-nitropropionic acid
Huntingtons disease
metabolic profiling
mitochondrial dysfunction
oxidative Stress
Issue Date: 1-Apr-2011
Citation: Chang, K.L., New, L.S., Mal, M., Goh, C.W., Aw, C.C., Browne, E.R., Chan, E.C.Y. (2011-04-01). Metabolic profiling of 3-nitropropionic acid early-stage huntingtons disease rat model using gas chromatography time-of-flight mass spectrometry. Journal of Proteome Research 10 (4) : 2079-2087. ScholarBank@NUS Repository.
Abstract: 3-Nitropropionic acid (3-NP), a potent irreversible inhibitor of mitochondrial complex II enzyme, leads to mitochondrial dysfunction and oxidative stress in Huntingtons 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. © 2011 American Chemical Society.
Source Title: Journal of Proteome Research
ISSN: 15353893
DOI: 10.1021/pr2000336
Appears in Collections:Staff Publications

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