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dc.contributor.authorMorel, Yulemni
dc.date.accessioned2024-02-02T14:32:46Z
dc.date.available2024-02-02T14:32:46Z
dc.date.issued2023
dc.identifier.urihttp://hdl.handle.net/10713/21335
dc.descriptionUniversity of Maryland, Baltimore, School of Pharmacy, Ph.D., 2023en_US
dc.description.abstractLipids encompass the major constituent of cellular membranes and are involved in various cellular processes such as membrane integrity, energy storage, and cellular signaling. Due to their structural composition, lipids are vulnerable to disruptions in redox biology, ultimately leading to lipid peroxidation (LPO) and detrimental alterations to membrane dynamics, interactions with membrane proteins, and signal transduction. Several disease states such as traumatic brain injury (TBI) are plagued by oxidative stress and LPO. Thus, an understanding of the lipid molecular targets is crucial for defining the underlying mechanisms driving pathology. Plasmalogen, a unique glycerophospholipid (GP) characterized by a vinyl ether bond at the sn-1 position, is a lipid structure with noteworthy redox-regulating properties. Reports have highlighted dysregulated levels of plasmalogen lipids following TBI-onset, with oxidative degradation products such as lysoglycerophospholipids accumulating. With their established importance, a comprehensive investigation of their oxidative role within TBI is lacking. Furthermore, the structural diversity of the lipidome and the extended lipid complexity due to LPO introduces challenges with the detection, identification, and quantification of these lipid structures. This research describes the development of analytical methodology for the detection, characterization, and quantification of plasmalogen and its oxidized derivatives across biological samples. Herein, a targeted quantitative assay was established to evaluate plasmalogen and its lysoplasmalogen/glycerophospholipid levels, and confirm its role as an early marker of acute brain injury. To investigate the unique oxidative properties of plasmalogen as compared to other lipid classes, liposomal mixtures were prepared, and displayed a significant vulnerability for lipids with the presence of a vinyl ether bond at the sn-1 position, a polyunsaturated fatty acid (PUFA) at the sn-2 position, and an ethanolamine headgroup (PE). After validating their oxidative potential, we further constructed a comprehensive analytical workflow that combined complementary LC separations, tandem mass spectrometry, and drift-tube ion mobility, which significantly improved our ability to tease apart the isomeric complexity of the oxidative lipidome. To establish their impact on the cellular environment, whole cells, purified lysosomes, and samples isolated from a TBI mouse model were investigated and revealed the formation of oxidized PE products that potentially alter organellular function and propagate disease pathology.en_US
dc.language.isoen_USen_US
dc.subject.meshLipid Peroxidationen_US
dc.subject.meshLipidomicsen_US
dc.subject.meshMass Spectrometryen_US
dc.subject.meshPhosphatidylethanolamineen_US
dc.subject.meshPlasmalogensen_US
dc.subject.meshBrain Injuries, Traumaticen_US
dc.titleIntegration of Quantitative and Qualitative Mass Spectrometric Workflows to Evaluate the Role of Plasmalogen Glycerophosphoethanolamine in Disease Progressionen_US
dc.typedissertationen_US
dc.date.updated2024-02-01T02:05:34Z
dc.language.rfc3066en
dc.contributor.advisorJones, Jace W., 1978-
refterms.dateFOA2024-02-02T14:32:47Z


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