Browsing by Subject "lipoprotein"
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Item Detection of oxidation in human serum lipoproteins(Texas A&M University, 2006-04-12) Myers, Christine LeeA method for the oxidation of lipoproteins in vitro was developed using the free radical initiator, 2,2?-azobis-(2-amidinopropane) dihydrochloride (AAPH). Following in vitro oxidation, the susceptibility to oxidation of the serum samples was studied using density gradient ultracentifugation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Shifts in mean buoyant density of the lipoprotein particles, specifically low density lipoprotein (LDL) and high density lipoprotein (HDL), were observed in the density profile following centrifugation. The degree of shift in the density proved to be proportional to the extent of oxidation. Changes in apolipoproteins were studied with MALDI-TOF-MS. Observed variations in the mass spectra include m/z shifts due to chemical modifications and change in isoform distributions. The oxidation procedure and analysis techniques were applied to a clinical application to study the effects of table grape consumption on lipoprotein susceptibility to oxidation. The main objective of the research, to show feasibility that these methods could be used in a clinical setting, was achieved.Item Investigations into Hyperlipidemia and its Possible Associations with Pancreatitis in Dogs(2012-07-16) Xenoulis, PanagiotisThe relationship between hyperlipidemia and pancreatitis remains obscure in dogs. The aim of the present study was to investigate any possible association between hyperlipidemia and pancreatitis in dogs. In the first part of the study, Miniature Schnauzers with hypertriglyceridemia were found to have significantly higher serum cPLI concentrations than Miniature Schnauzers with normal serum triglyceride concentrations (P=0.0001). Also, Miniature Schnauzers with severe hypertriglyceridemia (>862 mg/dL) had 4.5 times higher odds (P=0.0343) for having a serum cPLI concentration consistent with pancreatitis. In the second part of the study, 17 Miniature Schnauzers prospectively enrolled with a history of pancreatitis were significantly more likely to have hypertriglyceridemia (71 percent) after resolution of pancreatitis than 34 age-matched Miniature Schnauzers without a history of pancreatitis (33 percent; odds ratio=5.02; P=0.0163). For the third part of the study, assessment of the feasibility and usefulness of a novel density gradient ultracentrifugation method using NaBiEDTA for lipoprotein profiling in dogs was attempted. Density gradient ultracentrifugation using NaBiEDTA was found to be useful for the study of lipoprotein profiles in dogs. Significant differences were detected in the lipoprotein profiles (mainly involving TRL and specific LDL fractions) among healthy Miniature Schnauzers, dogs of various other breeds, and hypertriglyceridemic Miniature Schnauzers. In the fourth part of the study, the effect of a commercially available low-fat diet on serum lipid and pancreas-specific lipase (Spec cPL) concentrations and lipoprotein profiles in Miniature Schnauzers with primary hypertriglyceridemia was evaluated. The study diet was found to be effective in significantly reducing serum triglyceride and cholesterol concentrations and changing the lipoprotein profiles of the dogs studied within 2 months. However, there was no significant effect of the study diet on serum Spec cPL concentrations. In the last part of the study, serum triglyceride and cholesterol concentrations and lipoprotein profiles were compared between dogs with naturally occurring pancreatitis and healthy dogs. The majority of dogs with naturally occurring pancreatitis had normal serum triglyceride and cholesterol concentrations. Important differences were identified in lipoprotein profiles between dogs with pancreatitis (higher LDL2, LDL3, and LDL4 fractions and lower TRL, HDL2a, and HDL3c fractions) and healthy control dogs.Item Structural Study of Lipid-binding Proteins(2013-08-09) Tsai, Han-ChunTuberculosis and malaria are among the most deadly infectious diseases in the world. The prevalence in regions without well-established public health causes economical and financial burdens for both society and patients. There is an urgent need to find effective treatments due to the emergence of drug-resistant strains. The aim of the studies reported here was to gain knowledge from the protein structures that can lead to the elimination of these pathogens. In these studies, protein crystallography is the main method used to solve protein structure. Based on the protein structure, we used different methods to characterize the protein function of three lipid-binding proteins (LprG, LprA, and gp232), and to identify potent inhibitors against Plasmodium falciparum enoyl-ACP reductase (PfENR), a drug target protein involved in central lipid metabolism. To characterize the function of two lipid-binding proteins (LprG and LprA), liquid chromatography-mass spectrometry (LC-MS) was used to analyze the ligand extract. In the study of tail fiber protein from mycobacteriophage, we used protein sequence alignment to identify gp232 as a major tail fiber protein, which potentially binds to lipids on the cellular surface of mycobacteria. A pull-down assay and imaging methods (fluorescence microscopy and electron microscopy) were conducted to confirm the function of gp232. In the structural study of PfENR, the structure-activity relationships method was used to find potent inhibitors against PfENR, which would show stronger inhibition than the known inhibitor triclosan. The triclosan-like analogs with modification at the 5-position revealed a new binding site in PfENR that has great potential for improving the potency of inhibition. We found that two inhibitors containing the core structure of piperidine and tetrahydroquinoline reached this new binding site and were 10-fold more potent than triclosan. The structural study of PfENR provides structural insights into the inhibitor-binding site that can lead to the discovery of new drugs. The comprehensive knowledge that we gained from the structural studies of these lipid-binding proteins provide new information that could lead to a greater understanding of pathogen physiology or guide the discovery of effective treatments to eliminate the pathogens.