Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/19189
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Britz-McKibbin, Philip | - |
dc.contributor.author | D' Agostino, Lisa | - |
dc.date.accessioned | 2016-05-02T18:31:34Z | - |
dc.date.available | 2016-05-02T18:31:34Z | - |
dc.date.issued | 2010-09 | - |
dc.identifier.uri | http://hdl.handle.net/11375/19189 | - |
dc.description.abstract | <p> Biological thiols are a class of labile and redox-active metabolite with significant interest to biomedical research due to their involvement in redox mechanisms of cell signaling and physiological control. As a result of oxidative stress, levels of various reduced thiols and oxidized disulfides are altered, which disrupts major cellular regulation pathways modulating protein function and gene expression. Thus, analysis of thiols in biological fluids is essential for understanding the role of oxidative stress and thiol dysregulation in aging and human diseases. However, reliable ex-vivo thiol determination is challenging due to their low abundance and susceptibility to auto-oxidation and thiol-disulfide exchange reactions. In this thesis, capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) in conjunction with maleimide labeling is developed as an integrative strategy for comprehensive plasma thiol redox status analysis for metabolomics. Maleimide labeling helps to address both major constraints in thiol analysis by stabilizing free sulfhydryl groups as their thioether adducts while improving ionization efficiency and analytical sensitivity. This enhancement in ionization efficiency can be quantitatively predicted based on relative changes in fundamental physicochemical properties of thiols that occur upon covalent derivatization when using multivariate calibration. On-line sample preconcentration together with thiol-selective labeling using a cationic quaternary ammonium maleimide analog allowed for simultaneous analysis of reduced thiols and intact oxidized disulfides by CE-ESI-MS with low nanomolar detection limits of 8-30 nM. Improved identification of unknown low abundance thiols and other classes of polar metabolites is also demonstrated by prediction of relative migration times in CE that is complementary to ESI-MS. Comprehensive plasma thiol speciation together with untargeted profiling of polar metabolites provides a novel platform for holistic understanding of complex changes in metabolic networks associated with thiol dysregulation and/or nutritional intervention for the prevention or treatment of human disorders. </p> | en_US |
dc.language.iso | en | en_US |
dc.subject | plasma | en_US |
dc.subject | Biological thiols | en_US |
dc.subject | Redox Status | en_US |
dc.subject | Metabolomics | en_US |
dc.title | Comprehensive Assessment of Plasma Thiol Redox Status for Metabolomics | en_US |
dc.contributor.department | Chemistry | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
D'agostino_Lisa_A_2010_Masters.pdf | 12.66 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.