A5008316828- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cholesterol and Lipid Metabolism
- Lipoproteins and Cardiovascular Health
- Cancer, Lipids, and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and disorders
- Lipid metabolism and biosynthesis
- Adipokines, Inflammation, and Metabolic Diseases
- Protein Structure and Dynamics
- Metabolomics and Mass Spectrometry Studies
- Drug Transport and Resistance Mechanisms
- Regulation of Appetite and Obesity
- Atherosclerosis and Cardiovascular Diseases
- Diabetes and associated disorders
- Paraoxonase enzyme and polymorphisms
- thermodynamics and calorimetric analyses
- Adipose Tissue and Metabolism
- Advanced Proteomics Techniques and Applications
- Clinical Nutrition and Gastroenterology
- Protein Interaction Studies and Fluorescence Analysis
- Neuropeptides and Animal Physiology
- Diabetes Management and Research
- Lipid Membrane Structure and Behavior
- Cell Adhesion Molecules Research
- Biochemical Analysis and Sensing Techniques
University of Cincinnati
2016-2025
University of Cincinnati Medical Center
2010-2024
Simon Fraser University
1999-2018
Davidson College
2012-2018
The University of Texas Southwestern Medical Center
1977-2015
HemoShear (United States)
2015
Augusta University
2015
Cincinnati Children's Hospital Medical Center
2010-2015
Georgia Regents Medical Center
2015
Oncology Hematology Care
2015
α-Synuclein is a highly conserved presynaptic protein of unknown function. A mutation in the has been causally linked to Parkinson's disease humans, and normal an abundant component intraneuronal inclusions (Lewy bodies) characteristic disease. also precursor intrinsic extracellular plaques Alzheimer's The α-synuclein sequence largely composed degenerate 11-residue repeats reminiscent amphipathic α-helical domains exchangeable apolipoproteins. We hypothesized that should associate with...
Objective— Recent proteomic studies have identified multiple proteins that coisolate with human HDL. We hypothesized distinct clusters of protein components may distinguish between physicochemically-defined subpopulations HDL particles, and such exert specific biological function(s). Methods Results— investigated the distribution across 5 particle normolipidemic (HDL2b, 2a, 3a, 3b, 3c) fractionated by isopycnic density gradient ultracentrifugation. Liquid chromatography/electrospray mass...
Intestinal HDL is hepatoprotective High-density lipoprotein (HDL) important for cholesterol metabolism and may have anti-inflammatory antimicrobial properties. Although mainly produced by the liver, intestine also a source. Han et al. show in mice that intestinal not routed to systemic circulation. Rather, form of HDL3, it directly transported liver through hepatic portal vein. There, sequesters bacterial lipopolysaccharide from gut can trigger inflammation damage. In various models injury,...
Plasma levels of high density lipoprotein cholesterol (HDL-C) are inversely proportional to the incidence cardiovascular disease. Recent applications modern proteomic technologies have identified upward 50 distinct proteins associated with HDL particles many these newly discovered implicating in nonlipid transport processes including complement activation, acute phase response and innate immunity. However, almost all MS-based studies on date utilized gradient ultracentrifugation techniques...
Spherical high density lipoproteins (HDL) † predominate in human plasma. However, little information exists on the structure of most common HDL protein, apolipoprotein (apo) A-I, spheres vs. better studied discoidal forms. We produced spherical by incubating reconstituted with physiological plasma-remodeling enzymes and compared apoA-I discs comparable diameter (79–80 93–96 Å). Using cross-linking chemistry mass spectrometry, we determined that general structural organization was overall...
The goal of replenishing the cardiomyocyte (CM) population using regenerative therapies following myocardial infarction (MI) is hampered by limited regeneration capacity adult CMs, partially due to their withdrawal from cell cycle. Here, we show that microRNA-128 (miR-128) upregulated in CMs during postnatal switch proliferation terminal differentiation. In neonatal mice, cardiac-specific overexpression miR-128 impairs CM and cardiac function, while deletion extends enhancing expression...
Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine in response to fat absorption. Here we demonstrate a potential role for apoA-IV regulating glucose homeostasis. ApoA-IV–treated isolated pancreatic islets had enhanced insulin secretion under conditions of high but not low glucose, suggesting direct effect enhance glucose-stimulated release. This enhancement involves cAMP at level distal Ca 2+ influx into β cells. Knockout results compromised and impaired tolerance compared...
Plasma levels of low density lipoproteins (LDL) and high (HDL) exhibit opposing associations with cardiovascular disease in human populations mouse models have been heavily used to derive a mechanistic understanding these relationships. In humans, recent mass spectrometry studies revealed that the plasma lipoproteome is significantly more complex than originally appreciated. This particularly true for HDL which contains some 90 distinct proteins, majority play functional roles go beyond...
Abstract Platelet αIIbβ3 integrin and its ligands are essential for thrombosis hemostasis, play key roles in myocardial infarction stroke. Here we show that apolipoprotein A-IV (apoA-IV) can be isolated from human blood plasma using platelet β3 integrin-coated beads. Binding of apoA-IV to platelets requires activation integrin, the direct apoA-IV-αIIbβ3 interaction detected a single-molecule Biomembrane Force Probe. We identify aspartic acids 5 13 at N-terminus required binding which is...
Objective— HDL (high-density lipoprotein) in plasma is a heterogeneous group of lipoproteins typically containing apo AI as the principal protein. Most HDLs contain additional proteins from palate nearly 100 HDL-associated polypeptides. We hypothesized that some these define distinct and stable subspecies with unique proteomes drive function associations disease. Approach Results— produced 17 pools 80 normolipidemic human participants (32 men, 48 women; aged 21–66 years). Using...
Background The cholesterol efflux capacity of high density lipoprotein (HDL) is negatively associated with cardiovascular risk. Small HDL particles account almost quantitatively for capacity, perhaps mediated through and outer leaflet plasma membrane phospholipids by ABCA1 (ATP binding cassette subfamily A member 1). People type 1 diabetes are at increased coronary artery disease (CAD) risk despite normal HDL‐cholesterol concentrations. We therefore tested the hypothesis that small...
The antiatherogenic properties of apoA-IV suggest that this protein may act as an anti-inflammatory agent. We examined possibility in a mouse model acute colitis. Mice consumed 3% dextran sulfate sodium (DSS) their drinking water for 7 days, with or without daily intraperitoneal injections recombinant human apoA-IV. significantly and specifically delayed the onset, reduced severity extent of, DSS-induced inflammation, assessed by clinical disease activity score, macroscopic appearance...
High density lipoprotein (HDL) phospholipid (PL) fatty acyl chain composition has been proposed to affect the ability of HDL participate in first step reverse cholesterol transport. To examine effects PL acid length and degree unsaturation this process, reconstituted (rHDL) particles were made with human apolipoprotein (apo) A-I containing chains from 14 18 carbons length, which either fully saturated or unsaturated one both chains. These characterized structurally for their promote free...
Apolipoprotein AI (apoAI) is the principal protein constituent of high density lipoproteins and it plays a key role in human cholesterol homeostasis; however, structure apoAI not clearly understood. To test hypothesis that organized into domains, three deletion mutants expressed Escherichia coli were studied solution reconstituted lipoprotein particles. Each mutant lacked one specific regions together encompass almost entire 243 aa sequence native ( Δ44-126 , Δ139-170 Δ190-243 ). Circular...
The antiatherogenic properties of apoA-IV suggest that this protein may act as an anti-inflammatory agent. We examined possibility in a mouse model acute colitis. Mice consumed 3% dextran sulfate sodium (DSS) their drinking water for 7 days, with or without daily intraperitoneal injections recombinant human apoA-IV. significantly and specifically delayed the onset, reduced severity extent of, DSS-induced inflammation, assessed by clinical disease activity score, macroscopic appearance...
Objective— The purpose of this study was to understand the interactions apoA-I with cells expressing ABCA1. Methods and Results— binding wild-type (WT) mutant forms human mouse J774 macrophages examined. Analysis total at 37°C 125 I-WT specifically ABCA1, as determined by covalent cross-linking, revealed saturable high affinity in both cases. Determination level cell-surface expression ABCA1 showed that only about 10% associated cell surface bound directly Furthermore, when I -apoA-I...