Global Metabolomic and Isobaric Tagging Capillary Liquid Chromatography–Tandem Mass Spectrometry Approaches for Uncovering Pathway Dysfunction in Diabetic Mouse Aorta
| Autor: | Wei Yuan, Laura A. Filla, Shuwei Li, Eva L. Feldman, James L. Edwards |
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| Rok vydání: | 2014 |
| Předmět: |
Metabolite
Diabetic angiopathy Tandem mass spectrometry 01 natural sciences Biochemistry Article 03 medical and health sciences chemistry.chemical_compound Metabolomics isobaric tags Tandem Mass Spectrometry Liquid chromatography–mass spectrometry global metabolomics Diabetes mellitus diabetic complications medicine Metabolome Animals Amines Amino Acids metabolic pathway dysfunction Aorta 030304 developmental biology Mice Knockout 0303 health sciences diabetes 010401 analytical chemistry General Chemistry medicine.disease Vitamin B 6 capillary liquid chromatography 3. Good health 0104 chemical sciences Butyrates Metabolic pathway chemistry Hyperglycemia Isotope Labeling Carbohydrate Metabolism Propionates Biomarkers Diabetic Angiopathies Metabolic Networks and Pathways Chromatography Liquid |
| Zdroj: | Journal of Proteome Research |
| ISSN: | 1535-3907 1535-3893 |
| DOI: | 10.1021/pr501030e |
| Popis: | Despite the prevalence of diabetes and the global health risks it poses, the biochemical pathogenesis of diabetic complications remains poorly understood with few effective therapies. This study employs capillary liquid chromatography (capLC) and tandem mass spectrometry (MS/MS) in conjunction with both global metabolomics and isobaric tags specific to amines and carbonyls to probe aortic metabolic content in diabetic mice with hyperglycemia, hyperlipidemia, hypertension, and stenotic vascular damage. Using these combined techniques, metabolites well-characterized in diabetes as well as novel pathways were investigated. A total of 53,986 features were detected, 719 compounds were identified as having significant fold changes (thresholds ≥ 2 or ≤ 0.5), and 48 metabolic pathways were found to be altered with at least 2 metabolite hits in diabetic samples. Pathways related to carbonyl stress, carbohydrate metabolism, and amino acid metabolism showed the greatest number of metabolite changes. Three novel pathways with previously limited or undescribed roles in diabetic complications--vitamin B6, propanoate, and butanoate metabolism--were also shown to be altered in multiple points along the pathway. These discoveries support the theory that diabetic vascular complications arise from the interplay of a myriad of metabolic pathways in conjunction with oxidative and carbonyl stress, which may provide not only new and much needed biomarkers but also insights into novel therapeutic targets. |
| Databáze: | OpenAIRE |
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