- Diabetes, Cardiovascular Risks, and Lipoproteins
- Lipoproteins and Cardiovascular Health
- Cancer, Lipids, and Metabolism
- Alzheimer's disease research and treatments
- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and disorders
- Lipid metabolism and biosynthesis
- Nuclear Receptors and Signaling
- Glycosylation and Glycoproteins Research
- Protease and Inhibitor Mechanisms
- Ubiquitin and proteasome pathways
- Adipokines, Inflammation, and Metabolic Diseases
- Mitochondrial Function and Pathology
- Liver Disease Diagnosis and Treatment
- Retinoids in leukemia and cellular processes
- Atherosclerosis and Cardiovascular Diseases
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Advanced Proteomics Techniques and Applications
- Cellular transport and secretion
- Antioxidant Activity and Oxidative Stress
- Fatty Acid Research and Health
- Genetic Associations and Epidemiology
- S100 Proteins and Annexins
Gladstone Institutes
2010-2024
University of California, San Francisco
2009-2024
Marymount University
2016
National Institutes of Health
1974-2010
Amerikan Hastanesi
1993-2010
The University of Texas Southwestern Medical Center
1993-2010
University of Ottawa
2010
Medical Research Council
2010
GlaxoSmithKline (United Kingdom)
2010
University of Cambridge
2010
Abaract Plasma lipoprotein metabolism is regulated and controlled by the specific apolipoprotein (apo-) constituents of various classes.The major apolipoproteins include apoE, apoB, apoA-I, apoA-11, apoA-IV, apoC-I, apoC-11, apoC-Ill.Specific function in regulation through their involvement transport redistribution lipids among cells tissues, role as cofactors for enzymes lipid metabolism, or maintenance structure particles.The primary structures most are now known, functional domains these...
Apolipoprotein E4 (apoE4), one of the three common isoforms apoE, has been implicated in Alzheimer's disease. The effects apoE on neuronal growth were determined cultures dorsal root ganglion neurons. In presence β-migrating very low density lipoproteins (β-VLDL), apoE3 increased neurite outgrowth, whereas apoE4 decreased outgrowth. or β-VLDL prevented by incubation with a monoclonal antibody to reductive methylation both which block ability interact lipoprotein receptors. data suggest that...
The plasma protein apolipoprotein (apo) E is an important determinant of lipid transport and metabolism in mammals. In the present study, immunocytochemistry has been used to identify apo specific cells central peripheral nervous systems rat. Light microscopic examination revealed that all astrocytes, including specialized astrocytic (Bergmann glia cerebellum, tanycytes third ventricle, pituicytes neurohypophysis, Müller retina), possessed significant concentrations E. major subdivisions...
The abbreviations used are: apo-E, E apoprotein; VLDL, very low density lipoproteins; isoforms, E-1, E-2, E-3, and E-4, using the onedimensional gel nomenclature established by Utermann et al. (17).Equivalency of Zannis Breslow (20) with system: p-11 pattern, E-4/E-4 genotype; p-111 E-3/E-3 D-IV E-2/E-2 a-I1 E-4/E-3 a-111 E-3/E-2 a-IV E-4/E-2 genotype.and several different animals (5-10).Metabolically, this Mr ' Expressed as residues per mole, assuming Ala = 1.0 (2 determinations).Converted...
The amino acid sequence of human apolipoprotein E (apo-E) has been determined.Apo-E2, one the major isoforms E, is a polypeptide 299 acids having calculated molecular weight 34,145.The isoform apo-E3 differs from apo-E2 by single substitution arginine for cysteine at residue 158 (italicized).The sequqnce...
In summary, the model of chylomicron remnant clearance via LDL receptors, HSPG-LRP pathway, and HSPG alone appears to be valid (Fig. 1). Apolipoprotein E serves as major ligand facilitating lipoprotein catabolism. The in space Disse may well serve a reservoir allow apoE accumulate thereby participate sequestration capture lipoproteins. addition, receptor, either or part complex, responsible for endocytosis by hepatocytes. Along with receptor function an alternate pathway. Hepatic lipase...
Human apolipoprotein E, a blood plasma protein, mediates the transport and uptake of cholesterol lipid by way its high affinity interaction with different cellular receptors, including low-density lipoprotein (LDL) receptor. The three-dimensional structure LDL receptor-binding domain apoE has been determined at 2.5 angstrom resolution x-ray crystallography. protein forms an unusually elongated (65 angstroms) four-helix bundle, helices apparently stabilized tightly packed hydrophobic core...
The low density lipoprotein (LDL) cell surface receptors on human fibroblasts grown in culture bind specific plasma lipoproteins, initiating a series of events which regulate intracellular cholesterol metabolism. Specificity for the interaction with resides protein moieties specifically B and E apoproteins LDL certain high lipoproteins (HDLc HDLl), respectively. It was previously established that amino acid arginine is functionally significant residue or near recognition sites modification...
A 37-kDa glycoprotein has been described recently, whose synthesis is dramatically increased after injury of the rat sciatic and optic nerves. Cells in nerve sheath, distal to site injury, produce secrete large amounts this protein, so that by 3 weeks it represents 2-5% total soluble extracellular protein regenerating although fails accumulate damaged nerve. Results presented here reveal extensive homology between injury-induced a well-studied serum apolipoprotein E (apoE), involved lipid...
Recent work has demonstrated that apo E secretion and accumulation increase in the regenerating peripheral nerve. The fact apoE, conjunction with apoA-I LDL receptors, participates a well-established lipid transfer system raised possibility apoE is also involved transport injured In present study of crushed rat sciatic nerve, combination techniques was used to trace cellular associations apoA-I, receptor during nerve repair determine distribution at each stage. After crush injury, as axons...
Apolipoprotein (apo) E has roles beyond lipoprotein metabolism. The detrimental effects of apoE4 in cardiovascular, neurological, and infectious diseases correlate with its structural features (e.g., domain interaction) that distinguish it from apoE3 apoE2. Structure/function studies revealed apoE2 is severely defective LDL receptor binding because a difference alters the region helped unravel mechanism type III hyperlipoproteinemia. ApoE4 major genetic risk factor for Alzheimer's disease...
The relative amount of apolipoprotein (apo-) E mRNA in 12 different tissues the rat and marmoset was examined by dot blot hybridization using cloned cDNA probes. As expected, it found to be most abundant liver. However, substantial amounts apo-E were brain adrenals at levels about one-third that Significant quantities detected all other peripheral as well. these 2-10% liver 10-30% marmoset. Apo-E also human each species examined; distributed throughout major areas this organ. In contrast,...
Previous in vivo turnover studies suggested that retarded clearance of low density lipoproteins (LDL) from the plasma some hypercholesterolemic patients is due to LDL with defective receptor binding. The present study examined this postulate directly by binding experiments. a patient (G.R.) displayed reduced ability bind receptors on normal human fibroblasts. G.R. possessed 32% activity (approximately equal 9.3 micrograms per ml were required displace 50% 125I-labeled LDL, vs. approximately...