WorldWideScience

Sample records for apolipoprotein stabilized nanodisk

  1. Amphotericin B induced interdigitation of apolipoprotein stabilized nanodisk bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, T; Weers, P M; Sulchek, T; Hoeprich, P D; Ryan, R O

    2006-12-07

    Amphotericin B nanodisks (AMB-ND) are ternary complexes of AMB, phospholipid (PL) and apolipoprotein organized as discrete nanometer scale disk-shaped bilayers. In gel filtration chromatography experiments, empty ND lacking AMB elute as a single population of particles with a molecular weight in the range of 200 kDa. AMB-ND formulated at a 4:1 PL:AMB weight ratio, separated into two peaks. Peak 1 eluted at the position of control ND lacking AMB while the second peak, containing all of the AMB present in the original sample, eluted in the void volume. When ND prepared with increased AMB (1:1 phospholipid:AMB molar ratio) were subjected to gel filtration chromatography, an increased proportion of phospholipid and apolipoprotein were recovered in the void volume with the AMB. Prior to gel filtration the AMB-ND sample could be passed through a 0.22 {micro}m filter without loss of AMB while the voided material was lost. Native gel electrophoresis studies corroborated the gel permeation chromatography data. Far UV circular dichroism analyses revealed that apoA-I associated with AMB-ND denatures at a lower guanidine HCl concentration than apoA-I associated with ND lacking AMB. Atomic force microscopy revealed that AMB induces compression of the ND bilayer thickness consistent with bilayer interdigitation, a phenomenon that is likely related to the ability of AMB to induce pore formation in susceptible membranes.

  2. Curcumin nanodisks: formulation and characterization

    OpenAIRE

    Ghosh, Mistuni; Singh, Amareshwar T.K.; Xu, Wenwei; Sulchek, Todd; Gordon, Leo I.; Ryan, Robert O.

    2010-01-01

    Nanodisks (ND) are nanoscale, disk-shaped phospholipid bilayers whose edge is stabilized by apolipoproteins. In the present study, ND were formulated with the bioactive polyphenol, curcumin, at a 6:1 phospholipid:curcumin molar ratio. Atomic force microscopy revealed that curcumin-ND are particles with diameters

  3. Anti-CD20 single chain variable antibody fragment–apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas

    Science.gov (United States)

    Crosby, Natasha M.; Ghosh, Mistuni; Su, Betty; Beckstead, Jennifer A.; Kamei, Ayako; Simonsen, Jens B.; Luo, Bing; Gordon, Leo I.; Forte, Trudy M.; Ryan, Robert O.

    2015-01-01

    A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents. PMID:25994015

  4. Anti-CD20 single chain variable antibody fragment-apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas.

    Science.gov (United States)

    Crosby, Natasha M; Ghosh, Mistuni; Su, Betty; Beckstead, Jennifer A; Kamei, Ayako; Simonsen, Jens B; Luo, Bing; Gordon, Leo I; Forte, Trudy M; Ryan, Robert O

    2015-08-01

    A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents. PMID:25994015

  5. Metallic Graphene Nanodisks

    OpenAIRE

    Ezawa, Motohiko

    2007-01-01

    We explore the electronic properties of finite-length graphene nanoribbons as well as graphene nanodisks with various sizes and shapes in quest of metallic ones. For this purpose it is sufficient to search zero-energy states. We find that there exist no zero-energy states in finite-length zigzag nanoribbons though all infinite-length zigzag nanoribbons have zero-energy states. The occurrence of zero-energy states is surprisingly rare. Among typical nanodisks, only trigonal zigzag nanodisks ha...

  6. Graphene Nanoribbon and Graphene Nanodisk

    OpenAIRE

    Ezawa, Motohiko

    2007-01-01

    We study electronic properties of graphene derivatives which have closed edges. They are finite-length graphene nanoribbons and graphene nanodisks. No metallic states are found in finite-length zigzag nanoribbons though all infinite-length zigzag nanoribbons are metallic. We also study hexagonal, parallelogrammic and trigonal nanodisks with zigzag or armchair edges. No metallic states are found in these nanodisks either except trigonal zigzag nanodisks. It is interesting that we can design th...

  7. The Hsp110 molecular chaperone stabilizes apolipoprotein B from endoplasmic reticulum-associated degradation (ERAD).

    Science.gov (United States)

    Hrizo, Stacy L; Gusarova, Viktoria; Habiel, David M; Goeckeler, Jennifer L; Fisher, Edward A; Brodsky, Jeffrey L

    2007-11-01

    Apolipoprotein B (apoB) is the most abundant protein in low density lipoproteins and plays key roles in cholesterol homeostasis. The co-translational degradation of apoB is controlled by fatty acid levels in the endoplasmic reticulum (ER) and is mediated by the proteasome. To define the mechanism of apoB degradation, we employed a cell-free system in which proteasome-dependent degradation is recapitulated with yeast cytosol, and we developed an apoB yeast expression system. We discovered that a yeast Hsp110, Sse1p, associates with and stabilizes apoB, which contrasts with data indicating that select Hsp70s and Hsp90s facilitate apoB degradation. However, the Ssb Hsp70 chaperones have no effect on apoB turnover. To determine whether our results are relevant in mammalian cells, Hsp110 was overexpressed in hepatocytes, and enhanced apoB secretion was observed. This study indicates that chaperones within distinct complexes can play unique roles during ER-associated degradation (ERAD), establishes a role for Sse1/Hsp110 in ERAD, and identifies Hsp110 as a target to lower cholesterol. PMID:17823116

  8. Blocking TLR2 activity diminishes and stabilizes advanced atherosclerotic lesions in apolipoprotein E-deficient mice

    Institute of Scientific and Technical Information of China (English)

    Xiao-xing WANG; Xiao-xi LV; Jia-ping WANG; Hui-min YAN; Zi-yan WANG; Han-zhi LIU; Xiao-ming FU

    2013-01-01

    Aim:Toll-like receptor 2 (TLR2) signaling plays a critical role in the initiation of atherosclerosis.The aim of this study was to investigate whether blocking TLR2 activity could produce therapeutic effects on advanced atherosclerosis.Methods:Forty-week old apolipoprotein E-deficient (ApoE-/-) mice fed on a normal diet were intravenously injected with a TLR2-neutralizing antibody or with an isotype-matched IgG for 18 weeks.Double-knockout ApoE-/-Tlr2-/-mice were taken as a positive control.At the end of the treatments,the plasma lipid levels were measured,and the plaque morphology,pro-inflammatory cytokines expression and apoptosis in arteries were analyzed.In the second part of this study,6-week old ApoE-/-and ApoE-/-Tlr2-/-mice fed on a high-cholesterol diet for 12 to 24 weeks,the expression levels of TLR2 and apoptotic markers in arteries were examined.Results:Blockade of TLR2 activity with TLR2-neutralizing antibody or knockout of Tlr2 gene did not alter the plasma lipid levels in ApoE-/-mice.However,the pharmacologic and genetic manipulations significantly reduced the plaque size and vessel stenosis,and increased plaque stability in the brachiocephalic arteries.The protective effects of TLR2 antagonism were associated with the suppressed expression of pro-inflammatory cytokines IL-6 and TNF-α and the inactivation of transcription factors NF-KB and Stat3.In addition,blocking TLR2 activity attenuated ER stress-induced macrophage apoptosis in the brachiocephalic arteries,which could promote the resolution of necrotic cores in advanced atherosclerosis.Moreover,high-cholesterol diet more prominently accelerated atherosclerotic formation and increased the expression of pro-apoptotic protein CHOP and apoptosis in ApoE-/-mice than in ApoE-/-Tlr2-/-mice.Conclusion:The pharmacologic or genetic blockade of TLR2 activity diminishes and stabilizes advanced atherosclerotic lesions in ApoE-/-mice.Thus,targeting TLR2 signaling may be a promising therapeutic strategy against

  9. Multicolor generation using silicon nanodisk absorber

    International Nuclear Information System (INIS)

    A multicolored matrix that spans the visible range was demonstrated by using silicon nanodisk arrays. A nanostructured silicon substrate, which featured periodic silicon nanodisk arrays of various diameters, inter-nanodisk distances, and heights, was fabricated using electron-beam lithography and reactive ion etching. These silicon nanodisks were able to support HE1m leaky modes, which depended on the diameter of the nanodisks, resulting in wavelength-dependent reflection spectra. The resonant wavelength redshifted linearly with the increasing nanodisk diameter. The output color lay in the visible range and was observed to be tunable when varying the diameter, interdistance, and height. The results of finite-difference time-domain simulations exhibited close agreement with the observed optical properties of the periodic silicon nanodisk arrays

  10. Synthesis, characterization, and controlled aggregation of biotemplated polystyrene nanodisks

    International Nuclear Information System (INIS)

    Cross-linked polystyrene nanodisks were prepared by controlled polymerization of styrene and divinylbenzene in the interior of bicelles, discoidal lipid aggregates. Aggregation behavior of polymer nanodisks was studied in water, organic solvents, and solid phase. Nanodisks form stable dispersions in aqueous solutions of surfactants, such as sodium dodecyl sulfate (SDS). Varying SDS/nanodisk ratio allowed us to control the size of nanodisk aggregates. Nanodisks are readily solubilized in nonpolar organic solvents, such as toluene and carbon tetrachloride, to yield stable monodisperse suspensions. These findings open opportunities for creating nanodisk-based nanocomposite materials. Stable nanodisk suspension in toluene enabled small angle neutron scattering (SANS) measurements. SANS data confirmed the nanodisk diameter and allowed accurate measurement of nanodisk thickness (19.5 ± 1.0 Å). In solid phase, nanodisks aggregate in sub-micron platelets.

  11. Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice.

    Science.gov (United States)

    Zhang, Xilin; Hu, Jin; Zhong, Li; Wang, Na; Yang, Longyu; Liu, Chia-Chen; Li, Huifang; Wang, Xin; Zhou, Ying; Zhang, Yunwu; Xu, Huaxi; Bu, Guojun; Zhuang, Jiangxing

    2016-09-01

    Apolipoprotein E (apoE) is a major cholesterol carrier that regulates lipid homeostasis by mediating lipid transport from one tissue or cell type to another. In the central neural system (CNS), apoE is mainly produced by astrocytes, and transports cholesterol to neurons via apoE receptors, which are members of the low-density lipoprotein receptor family. The APOEε4 gene is a strong genetic risk factor for late-onset sporadic Alzheimer's disease (AD), likely through its strong effect on the accumulation of amyloid-β (Aβ) peptide. ApoE protein levels in cerebrospinal fluid (CSF) and plasma are reduced in APOEε4 carriers and in patients with AD. Furthermore, altered cholesterol levels are also associated with the risk of AD. Aβ accumulation, oligomerization and deposition in the brain are central to the pathogenesis of AD. Mounting evidence demonstrates that apoE and apoE receptors play important roles in these processes. Astrocyte-derived apoE is pivotal for cerebral cholesterol metabolism and clearance of Aβ. Thus, we hypothesized that increased apoE in the brain may be an effective therapeutic strategy for AD. We report here that quercetin can significantly increase apoE levels by inhibiting apoE degradation in immortalized astrocytes. Importantly, we show that oral administration of quercetin significantly increased brain apoE and reduced insoluble Aβ levels in the cortex of 5xFAD amyloid model mice. Our results demonstrate that quercetin increases apoE levels through a novel mechanism and can be explored as a novel class of drug for AD therapy. PMID:27114256

  12. Substrate-induced strain in carbon nanodisks

    International Nuclear Information System (INIS)

    Graphitic nanodisks of typically 20–50 nm in thickness, produced by the so-called Kvaerner Carbon Black and Hydrogen Process were dispersed on gold substrate and investigated by atomic force microscopy (AFM), field emission scanning electron microscopy (FE-SEM), and confocal Raman spectroscopy. The roughness of the gold surface was drastically changed by annealing at 400 °C. AFM measurements show that this change in the surface roughness induces changes also in the topography of the nanodisks, as they closely follow the corrugation of the gold substrate. This leads to strained nanodisks, which is confirmed also by confocal Raman microscopy. We found that the FE-SEM contrast obtained from the disks depends on the working distance used during the image acquisition by In-lens detection, a phenomenon which we explain by the decrease in the amount of electrons reaching the detector due to diffraction. This process may affect the image contrast in the case of other layered materials, like hexagonal boron nitride, and other planar hybrid nanostructures, too. - Highlights: • Bending of carbon nanodisks is induced by the roughness of the gold substrate. • Confocal Raman microscopy shows a compressive strain induced in the nanodisks. • The electron microscopy contrast of nanodisks depends on the working distance

  13. Dissipative plasmon solitons in graphene nanodisk arrays

    CERN Document Server

    Smirnova, Daria A; Smirnov, Lev A; Kivshar, Yuri S

    2014-01-01

    We study nonlinear modes in one-dimensional arrays of doped graphene nanodisks with Kerr-type nonlinear response in the presence of an external electric field. We present the theoretical model describing the evolution of the disks' polarizations, taking into account intrinsic graphene losses and dipole-dipole coupling between the graphene nanodisks. We reveal that this nonlinear system can support discrete dissipative scalar solitons of both longitudinal and transverse polarizations, as well as vector solitons composed of two mutually coupled polarization components. We demonstrate the formation of stable resting and moving localized modes under controlling guidance of the external driving field.

  14. Classical and quantum plasmonics in graphene nanodisks

    DEFF Research Database (Denmark)

    Christensen, Thomas; Wang, Weihua; Jauho, Antti-Pekka;

    2014-01-01

    Edge states are ubiquitous for many condensed matter systems with multicomponent wave functions. For example, edge states play a crucial role in transport in zigzag graphene nanoribbons. Here, we report microscopic calculations of quantum plasmonics in doped graphene nanodisks with zigzag edges. We...

  15. Localized plasmons in bilayer graphene nanodisks

    DEFF Research Database (Denmark)

    Wang, Weihua; Xiao, Sanshui; Mortensen, N. Asger

    2016-01-01

    We study localized plasmonic excitations in bilayer graphene (BLG) nanodisks, comparing AA-stacked and AB-stacked BLG and contrasting the results to the case of two monolayers without electronic hybridization. The electrodynamic response of the BLG electron gas is described in terms of a spatially...

  16. Apolipoprotein M

    OpenAIRE

    Nilsson-Ehle Peter; Zhang Xiaoying; Luo Guanghua; Xu Ning

    2004-01-01

    Abstract Apolipoprotein M (apoM) is a 26-kDa protein that is mainly associated with high-density lipoprotein (HDL) in human plasma, with a small proportion present in triglyceride-rich lipoproteins (TGRLP) and low-density lipoproteins (LDL). Human apoM gene is located in p21.31 on chromosome 6 (chromosome 17, in mouse). Human apoM cDNA (734 base pairs) encodes 188-amino acid residue-long protein. It belongs to lipocalin protein superfamily. Human tissue expression array study indicates that a...

  17. Morphing a Plasmonic Nanodisk into a Nanotriangle

    OpenAIRE

    Schmidt, Franz P.; Ditlbacher, Harald; Hofer, Ferdinand; Krenn, Joachim R; Hohenester, Ulrich

    2014-01-01

    We morph a silver nanodisk into a nanotriangle by producing a series of nanoparticles with electron beam lithography. Using electron energy loss spectroscopy (EELS), we map out the plasmonic eigenmodes and trace the evolution of edge and film modes during morphing. Our results suggest that disk modes, characterized by angular order, can serve as a suitable basis for other nanoparticle geometries and are subject to resonance energy shifts and splittings, as well as to hybridization upon morphi...

  18. Localized plasmons in bilayer graphene nanodisks

    Science.gov (United States)

    Wang, Weihua; Xiao, Sanshui; Mortensen, N. Asger

    2016-04-01

    We study localized plasmonic excitations in bilayer graphene (BLG) nanodisks, comparing AA-stacked and AB-stacked BLG and contrasting the results to the case of two monolayers without electronic hybridization. The electrodynamic response of the BLG electron gas is described in terms of a spatially homogeneous surface conductivity, and an efficient alternative two-dimensional electrostatic approach is employed to carry out all the numerical calculations of plasmon resonances. Due to unique electronic band structures, the resonance frequency of the traditional dipolar plasmonic mode in the AA-stacked BLG nanodisk is roughly doping independent in the low-doping regime, while the mode is highly damped as the Fermi level approaches the interlayer hopping energy γ associated with tunneling of electrons between the two layers. In addition to the traditional dipolar mode, we find that the AB-stacked BLG nanodisk also hosts a new plasmonic mode with energy larger than γ . This mode can be tuned by either the doping level or structural size, and, furthermore, this mode can dominate the plasmonic response for realistic structural conditions.

  19. Estrogen-dependent activation of the avian very low density apolipoprotein II and vitellogenin genes. Transient alterations in mRNA polyadenylation and stability early during induction.

    Science.gov (United States)

    Cochrane, A W; Deeley, R G

    1988-10-01

    Administration of estrogen to egg-laying vertebrates activates unscheduled, hepatic expression of major, egg-yolk protein genes in immature animals and mature males. Two avian yolk protein genes, encoding very low density apolipoprotein II (apoVLDLII) and vitellogenin II, are dormant prior to stimulation with estrogen, but within three days their cognate mRNAs accumulate to become two of the most abundant species in the liver. Accumulation of these mRNAs has been attributed to both induction of transcription and selective, estrogen-dependent mRNA stabilization. We have detected alterations in the size of apoVLDLII mRNA that occur during the first 24 hours that are attributable to a shift in the extent of polyadenylation as steady-state is approached. In vitro transcription assays indicate that primary activation of both genes takes place relatively slowly and that maximal rates of mRNA accumulation occur when the apoVLDLII and vitellogenin II genes are expressed at only 30% and 10% of their fully induced levels, respectively. Transcription data combined with the structural alteration of apoVLDLII mRNA suggest that stability of the two mRNAs may change as steady-state is approached. We have assessed the compatibility of this suggestion with earlier estimates of the kinetics of accumulation of both mRNAs by developing a generally useful algorithm that predicts approach to steady-state kinetics under conditions where both the rate of synthesis and mRNA stability change throughout the accumulation phase of the response. The results predict that the stability of both mRNAs decreases by at least two- to threefold during the approach to steady-state and that, although an additional destabilization of apoVLDLII mRNA may occur following withdrawal of estrogen, the steady-state stability of vitellogenin mRNA is not significantly decreased upon removal of hormone. PMID:3210227

  20. Apolipoprotein M

    Directory of Open Access Journals (Sweden)

    Nilsson-Ehle Peter

    2004-10-01

    Full Text Available Abstract Apolipoprotein M (apoM is a 26-kDa protein that is mainly associated with high-density lipoprotein (HDL in human plasma, with a small proportion present in triglyceride-rich lipoproteins (TGRLP and low-density lipoproteins (LDL. Human apoM gene is located in p21.31 on chromosome 6 (chromosome 17, in mouse. Human apoM cDNA (734 base pairs encodes 188-amino acid residue-long protein. It belongs to lipocalin protein superfamily. Human tissue expression array study indicates that apoM is only expressed in liver and in kidney and small amounts are found in fetal liver and kidney. In situ apoM mRNA hybridization demonstrates that apoM is exclusively expressed in the hepatocytes and in the tubule epithelial cells in kidney. Expression of apoM could be regulated by platelet activating factor (PAF, transforming growth factors (TGF, insulin-like growth factor (IGF and leptin in vivo and/or in vitro. It has been demonstrated that apoM expression is dramatically decreased in apoA-I deficient mouse. Hepatocyte nuclear factor-1α (HNF-1α is an activator of apoM gene promoter. Deficiency of HNF-1α mouse shows lack of apoM expression. Mutations in HNF-1α (MODY3 have reduced serum apoM levels. Expression of apoM is significantly decreased in leptin deficient (ob/ob mouse or leptin receptor deficient (db/db mouse. ApoM concentration in plasma is positively correlated to leptin level in obese subjects. These may suggest that apoM is related to the initiation and progression of MODY3 and/or obesity.

  1. Rapid thermal synthesis of GaN nanocrystals and nanodisks

    Czech Academy of Sciences Publication Activity Database

    Sofer, Z.; Sedmidubský, D.; Huber, Š.; Šimek, P.; Šaněk, F.; Jankovský, O.; Gregorová, E.; Fiala, R.; Matějková, Stanislava; Mikulics, M.

    2013-01-01

    Roč. 15, č. 1 (2013), 1411/1-1411/7. ISSN 1388-0764 Institutional support: RVO:61388963 Keywords : gallium nitride * thermal ammonolysis * nanodisks * nanocrystals Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.278, year: 2013

  2. Morphing a plasmonic nanodisk into a nanotriangle.

    Science.gov (United States)

    Schmidt, Franz P; Ditlbacher, Harald; Hofer, Ferdinand; Krenn, Joachim R; Hohenester, Ulrich

    2014-08-13

    We morph a silver nanodisk into a nanotriangle by producing a series of nanoparticles with electron beam lithography. Using electron energy loss spectroscopy (EELS), we map out the plasmonic eigenmodes and trace the evolution of edge and film modes during morphing. Our results suggest that disk modes, characterized by angular order, can serve as a suitable basis for other nanoparticle geometries and are subject to resonance energy shifts and splittings, as well as to hybridization upon morphing. Similar to the linear combination of atomic orbitals (LCAO) in quantum chemistry, we introduce a linear combination of plasmonic eigenmodes to describe plasmon modes in different geometries, hereby extending the successful hybridization model of plasmonics. PMID:25000389

  3. Rapid thermal synthesis of GaN nanocrystals and nanodisks

    Energy Technology Data Exchange (ETDEWEB)

    Sofer, Zdenek, E-mail: zdenek.sofer@vscht.cz; Sedmidubsky, David; Huber, Stepan; Simek, Petr; Sanek, Filip; Jankovsky, Ondrej [Institute of Chemical Technology Prague, Department of Inorganic Chemistry (Czech Republic); Gregorova, Eva [Institute of Chemical Technology Prague, Department of Glass and Ceramics (Czech Republic); Fiala, Roman [Charles University, Faculty of Mathematics and Physics (Czech Republic); Matejkova, Stanislava [Institute of Organic Chemistry and Biochemistry of the ASCR, v.v.i (Czech Republic); Mikulics, Martin [PGI-9, Peter Gruenberg Institute, Forschungszentrum Juelich (Germany)

    2013-01-15

    Gallium nitride materials are at the forefront of nanoelectronic research due to their importance for UV optoelectronics. In this contribution, we present a facile and well-controlled synthesis of GaN nanodisks by rapid thermal ammonolysis of complex gallium fluoride precursor. We observed the formation of GaN nanodisks in 150 s at 800 Degree-Sign C. The structural properties of GaN were investigated by X-ray diffraction, Raman spectroscopy, and micro-photoluminescence. The morphology of GaN was investigated by scanning electron microscopy and the magnetic properties by superconducting quantum interference device (SQUID) techniques. The morphology of nanodisks was strongly influenced by the temperature of synthesis. The structure characterization shows a high concentration of defects related mainly to the vacancies of N and Ga. The magnetic measurement by SQUID shows paramagnetic behavior induced by structure defects. These findings have a strong implication on the construction of modern optoelectronic nanodevices.

  4. Ordered Au Nanodisk and Nanohole Arrays: Fabrication and Applications

    KAUST Repository

    Zheng, Yue Bing

    2010-01-01

    We have utilized nanosphere lithography (NSL) to fabricate ordered Au nanodisk and nanohole arrays on substrates and have studied the localized surface plasmon resonance (LSPR) of the arrays. Through these investigations, we demonstrate that the angle- dependent behavior of the LSPR in the Au nanodisk arrays enables real-time observation of exciton-plasmon couplings. In addition, we show that the NSL-fabricated Au nanohole arrays can be applied as templates for patterning micro-/nanoparticles under capillary force. The unique structural and plasmonic characteristics of the Au nanodisk and nano- hole arrays, as well as the low-cost and high-throughput NSL-based nanofabrication technique, render these arrays excellent platforms for numerous engineering applications. © 2010 by ASME.

  5. Electron-beam driven relaxation oscillations in ferroelectric nanodisks

    International Nuclear Information System (INIS)

    Using a combination of computational simulations, atomic-scale resolution imaging and phenomenological modelling, we examine the underlying mechanism for nanodomain restructuring in lead zirconate titanate nanodisks driven by electron beams. The observed subhertz nanodomain dynamics are identified with relaxation oscillations where the charging/discharging cycle time is determined by saturation of charge traps and nanodomain wall creep. These results are unusual in that they indicate very slow athermal dynamics in nanoscale systems, and possible applications of gated versions are discussed

  6. Electron-beam driven relaxation oscillations in ferroelectric nanodisks

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Nathaniel; Ahluwalia, Rajeev [Institute of High Performance Computing, Singapore 138632 (Singapore); Kumar, Ashok [CSIR-National Physical Laboratory, Delhi 110012 (India); Srolovitz, David J. [Department of Materials Science and Engineering and Department of Mechanical Engineering and Applied Mechanics, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Chandra, Premala [Department of Physics and Astronomy, Center for Materials Theory, Rutgers University, Piscataway, New Jersey 08854 (United States); Scott, James F. [Department of Physics, Cavendish Laboratory, J. J. Thompson Avenue, Cambridge CB3 0HE (United Kingdom); Department of Chemistry and Department of Physics, University of St. Andrews, St. Andrews YX16 9ST (United Kingdom)

    2015-10-12

    Using a combination of computational simulations, atomic-scale resolution imaging and phenomenological modelling, we examine the underlying mechanism for nanodomain restructuring in lead zirconate titanate nanodisks driven by electron beams. The observed subhertz nanodomain dynamics are identified with relaxation oscillations where the charging/discharging cycle time is determined by saturation of charge traps and nanodomain wall creep. These results are unusual in that they indicate very slow athermal dynamics in nanoscale systems, and possible applications of gated versions are discussed.

  7. Dynamically tunable Fano resonance in periodically asymmetric graphene nanodisk pair

    OpenAIRE

    Zhang, Zhengren; Su, Xiaopeng; Fan, Yuancheng; Yin, Pengfei; Zhang, Liwei; Shi, Xi

    2015-01-01

    We present a dynamically frequency tunable Fano resonance planar device composed of periodically asymmetric graphene nanodisk pair for the mid-infrared region. There are two kinds of modes in this structure, that is, the symmetric mode and the antisymmetric mode. The resonance coupling between the symmetric and antisymmetric modes creates a classical Fano resonance. Both of the Fano resonance amplitude and frequency of the structure can be dynamically controlled by varying the Fermi energy of...

  8. Magnetic ordering of systems of nanodisks with quenched positional disorder

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, Juan J [Fisica Aplicada I, Universidad de Malaga, 29071 Malaga (Spain); Alles, B, E-mail: jjalonso@uma.es, E-mail: alles@df.unipi.it [INFN-Sezione di Pisa, Largo Pontecorvo 3, 56127 Pisa (Italy)

    2011-04-06

    The effect of positional disorder in systems of single domain ferromagnetic nanodisks placed on a two-dimensional square lattice is studied by Monte Carlo simulations. Nanodisks are treated as magnetic dipoles pointing along one of the two principal axes of the lattice. Disorder is introduced displacing each nanodisk by ({delta}x, {delta}y) from its regular lattice position, where {delta}x is randomly chosen within the interval 0 {<=} {delta}x {<=} {Delta} and analogously for {delta}y. Two different regimes are found: for {Delta} < {Delta}{sub 0} = 0.18(2) (in units of lattice spacing) a thermally driven transition between a paramagnetic and a dipolar antiferromagnetic phase with a critical exponent {alpha}/{nu} changing continuously with {Delta}; for {Delta} {>=} {Delta}{sub 0} a paramagnetic phase covering the whole T > 0 range. Plots of the spin-glass overlap parameter versus temperature T or lattice size L seem to exclude an equilibrium spin-glass phase in the latter regime.

  9. Unconventional spin distributions in thick Ni80Fe20 nanodisks

    Science.gov (United States)

    Kumar, D.; Lupo, P.; Haldar, A.; Adeyeye, A. O.

    2016-05-01

    We study the spin distributions in permalloy (Py: Ni80Fe20) nanodisks as a function of diameter D (300 nm ≤ D ≤ 1 μm) and thickness L (30 nm ≤ L ≤ 100 nm). We observed that beyond a certain thickness, for a fixed disk diameter, an unconventional spin topology precipitates which is marked by the presence of a divergence field within the magnetic vortex curl. The strength of this divergence changes anti-symmetrically from negative to positive—depending on the core polarity—along the axis of the cylindrical nanodisk. This is also accompanied by a skyrmion-like out-of-plane bending of the spin vectors farther away from the disk center. Additionally, the vortex core dilates significantly when compared to its typical size. This has been directly observed using magnetic force microscopy. We determined from the ferromagnetic resonance spectroscopy measurements that the unconventional topology in the thicker nanodisks gyrated at a frequency, which is significantly lower than what is predicted by a magnetic vortex based analytical model. Micromagnetic simulations involving dipolar and exchange interactions appear to satisfactorily reproduce the experimentally observed static and dynamic behaviors. Besides providing a physical example of an unconventional topology, these results can also aid the design of topologically protected memory elements.

  10. Effects of external magnetic field and magnetic anisotropy on chiral spin structures of square nanodisks investigated with a quantum simulation approach

    Science.gov (United States)

    Liu, Zhaosen; Ian, Hou

    2016-04-01

    We employed a quantum simulation approach to investigate the magnetic properties of monolayer square nanodisks with Dzyaloshinsky-Moriya (DM) interaction. The computational program converged very quickly, and generated chiral spin structures on the disk planes with good symmetry. When the DM interaction is sufficiently strong, multi-domain structures appears, their sizes or average distance between each pair of domains can be approximately described by a modified grid theory. We further found that the external magnetic field and uniaxial magnetic anisotropy both normal to the disk plane lead to reductions of the total free energy and total energy of the nanosystems, thus are able to stabilize and/or induce the vortical structures, however, the chirality of the vortex is still determined by the sign of the DM interaction parameter. Moreover, the geometric shape of the nanodisk affects the spin configuration on the disk plane as well.

  11. Parametric pumping of precession modes in ferromagnetic nanodisks

    Science.gov (United States)

    Guo, Feng; Belova, L. M.; McMichael, R. D.

    2014-03-01

    We report on the parametric excitation of magnetic precession modes in nanodisks using a parallel pumping configuration. The excitations are detected using a ferromagnetic resonance force microscopy method, and the parallel-pumped spectra reveal nonlinear characteristics including instability thresholds and multiple, narrow, sawtooth-shaped resonances. These characteristics are in accord with analytical theory and micromagnetic modeling results. Modeled mode profiles of the excitations show that higher-order standing spin-wave modes with both even and odd symmetries are excited under parallel pumping.

  12. Synthesis of hcp-Co nanodisks

    Energy Technology Data Exchange (ETDEWEB)

    Puntes, Victor F.; Zanchet, Daniela; Erdonmez, Can K.; Alivisatos, A.P.

    2002-06-11

    hcp Co disk-shaped nanocrystals were obtained by rapid decomposition of cobalt carbonyl in presence of linear amines. Other surfactants, in addition to the amines, like phosphine oxides and oleic acid were used to improve size dispersion, shape control and nanocrystal stability. Co disks are ferromagnetic in character and they spontaneously self-assemble into long ribbons. X-ray and electron diffraction, electron microscopy and SQUID magnetometry have been employed to characterize this material.

  13. Efficient broad- and tunable-bandwidth optical extinction via aspect-ratio-tailored silver nanodisks

    CERN Document Server

    Anquillare, Emma L; Hsu, Chia Wei; DeLacy, Brendan G; Joannopoulos, John D; Soljacic, Marin

    2015-01-01

    Sub-wavelength resonators typically exhibit a narrow-bandwidth response to optical excitations. We computationally design and experimentally synthesize tailored distributions of silver nanodisks to extinguish light over broad, tunable frequency windows. We show that metallic nanodisks are two- to twenty-times more efficient in absorbing and scattering light than common structures. Per-volume efficiency increases away from the plasma frequency of the underlying metal. We measure broadband extinction per volume that closely approaches theoretical predictions over three representative visible-range wavelength windows, confirming the high efficiency of nanodisks and demonstrating the collective power of computational design and experimental precision for developing new photonics technologies.

  14. Efficient, designable, and broad-bandwidth optical extinction via aspect-ratio-tailored silver nanodisks

    CERN Document Server

    Anquillare, E L; Hsu, C W; DeLacy, B G; Joannopoulos, J D; Johnson, S G; Soljacic, M

    2016-01-01

    Subwavelength resonators, ranging from single atoms to metallic nanoparticles, typically exhibit a narrow-bandwidth response to optical excitations. We computationally design and experimentally synthesize tailored distributions of silver nanodisks to extinguish light over broad and varied frequency windows. We show that metallic nanodisks are two-to-ten-times more efficient in absorbing and scattering light than common structures, and can approach fundamental limits to broadband scattering for subwavelength particles. We measure broadband extinction per volume that closely approaches theoretical predictions over three representative visible-range wavelength windows, confirming the high efficiency of nanodisks and demonstrating the collective power of computational design and experimental precision for developing new photonics technologies.

  15. High efficiency silicon nanodisk laser based on colloidal CdSe/ZnS QDs

    Directory of Open Access Journals (Sweden)

    Min-Hsiung Shih

    2011-07-01

    Full Text Available Using colloidal CdSe/ZnS quantum dots in the submicron-sized silicon disk cavity, we have developed a visible wavelength nanodisk laser that operates under extremely low threshold power at room temperature. Time-resolved photoluminescence (PL of QDs; nanodisk by e-beam lithography. Observation of lasing action at 594 nm wavelength for quantum dots on a nanodisk (750 nm in diameter cavity and an ultra-low threshold of 2.8 µW. From QD concentration dependence studies we achieved nearly sevenfold increase in spontaneous emission (SE rate. We have achieved high efficient and high SE coupling rate in such a QD nanodisk laser.

  16. Efficient, designable, and broad-bandwidth optical extinction via aspect-ratio-tailored silver nanodisks

    OpenAIRE

    Anquillare, E. L.; Miller, O D; Hsu, C. W.; DeLacy, B. G.; Joannopoulos, J. D.; Johnson, S. G.; Soljacic, M.

    2016-01-01

    Subwavelength resonators, ranging from single atoms to metallic nanoparticles, typically exhibit a narrow-bandwidth response to optical excitations. We computationally design and experimentally synthesize tailored distributions of silver nanodisks to extinguish light over broad and varied frequency windows. We show that metallic nanodisks are two-to-ten-times more efficient in absorbing and scattering light than common structures, and can approach fundamental limits to broadband scattering fo...

  17. Shape dependent magnetic and optical properties in silicene nanodisks: A first principles study

    Science.gov (United States)

    Chowdhury, Suman; Nath, Palash; Jana, Debnarayan

    2015-08-01

    We report the optical anisotropy of four differently shaped silicene nanodisks within the framework of density functional theory in the long wavelength limit (q → 0). The calculations of density of states of all these nanodisks reveal clearly that zigzag trigonal (ZT) nanodisk has the maximum magnetic moment of 3.969μB. Further, the calculations related to optical properties indicate that the static value of real part of the dielectric constant and the real part of the refractive index assume maximum values for diamond shaped (DS) nanodisk in perpendicular polarization of the applied external electromagnetic (EM) field. However, in case of parallel polarization, significant changes in the static real part of dielectric constant and static refractive index are observed. Zero reflectivity is noticed around 3 eV and 5 eV for all nanodisks in parallel polarizations. Electron energy loss spectroscopy study reveals a presence of strong (intense) peak at 9 eV in perpendicular polarizations for all nanodisks. All these study may shed light on device fabrication in nano-opto-electronic technology and material characterization techniques.

  18. Light-Emitting Devices Based on Top-down Fabricated GaAs Quantum Nanodisks

    Science.gov (United States)

    Higo, Akio; Kiba, Takayuki; Tamura, Yosuke; Thomas, Cedric; Takayama, Junichi; Wang, Yunpeng; Sodabanlu, Hassanet; Sugiyama, Masakazu; Nakano, Yoshiaki; Yamashita, Ichiro; Murayama, Akihiro; Samukawa, Seiji

    2015-03-01

    Quantum dots photonic devices based on the III-V compound semiconductor technology offer low power consumption, temperature stability, and high-speed modulation. We fabricated GaAs nanodisks (NDs) of sub-20-nm diameters by a top-down process using a biotemplate and neutral beam etching (NBE). The GaAs NDs were embedded in an AlGaAs barrier regrown by metalorganic vapor phase epitaxy (MOVPE). The temperature dependence of photoluminescence emission energies and the transient behavior were strongly affected by the quantum confinement effects of the embedded NDs. Therefore, the quantum levels of the NDs may be tuned by controlling their dimensions. We combined NBE and MOVPE in a high-throughput process compatible with industrial production systems to produce GaAs NDs with tunable optical characteristics. ND light emitting diode exhibited a narrow spectral width of 38 nm of high-intensity emission as a result of small deviation of ND sizes and superior crystallographic quality of the etched GaAs/AlGaAs layer.

  19. Apolipoprotein AI tertiary structures determine stability and phospholipid-binding activity of discoidal high-density lipoprotein particles of different sizes.

    Science.gov (United States)

    Chen, Bin; Ren, Xuefeng; Neville, Tracey; Jerome, W Gray; Hoyt, David W; Sparks, Daniel; Ren, Gang; Wang, Jianjun

    2009-05-01

    Human high-density lipoprotein (HDL) plays a key role in the reverse cholesterol transport pathway that delivers excess cholesterol back to the liver for clearance. In vivo, HDL particles vary in size, shape and biological function. The discoidal HDL is a 140-240 kDa, disk-shaped intermediate of mature HDL. During mature spherical HDL formation, discoidal HDLs play a key role in loading cholesterol ester onto the HDL particles by activating the enzyme, lecithin:cholesterol acyltransferase (LCAT). One of the major problems for high-resolution structural studies of discoidal HDL is the difficulty in obtaining pure and, foremost, homogenous sample. We demonstrate here that the commonly used cholate dialysis method for discoidal HDL preparation usually contains 5-10% lipid-poor apoAI that significantly interferes with the high-resolution structural analysis of discoidal HDL using biophysical methods. Using an ultracentrifugation method, we quickly removed lipid-poor apoAI. We also purified discoidal reconstituted HDL (rHDL) into two pure discoidal HDL species of different sizes that are amendable for high-resolution structural studies. A small rHDL has a diameter of 7.6 nm, and a large rHDL has a diameter of 9.8 nm. We show that these two different sizes of discoidal HDL particles display different stability and phospholipid-binding activity. Interestingly, these property/functional differences are independent from the apoAI alpha-helical secondary structure, but are determined by the tertiary structural difference of apoAI on different discoidal rHDL particles, as evidenced by two-dimensional NMR and negative stain electron microscopy data. Our result further provides the first high-resolution NMR data, demonstrating a promise of structural determination of discoidal HDL at atomic resolution using a combination of NMR and other biophysical techniques. PMID:19384992

  20. Normal and anomalous plasmonic lattice modes of gold nanodisk arrays in inhomogeneous media

    Science.gov (United States)

    Sadeghi, S. M.; Wing, W. J.; Campbell, Q.

    2016-03-01

    We study plasmonic lattice modes in two dimensional arrays of large metallic nanodisks in strongly inhomogeneous environments with controlled dielectric asymmetries. This is done within the two limits of positive (air/substrate) and negative (Si/substrate) asymmetries. In the former, the nanodisks are exposed to air, while in the latter, they are fully embedded in a dielectric material with a refractive index much higher than that of the glass substrate (Si). Our results show that in the air/substrate limit, the arrays can mainly support two distinct visible and infrared peaks associated with the optical coupling of multipolar plasmonic resonances of nanodisks in air and substrate (normal modes). As the nanodisks are gradually embedded in Si, i.e., going from the positive to negative asymmetry limit, the visible peak undergoes more than 200 nm red shift without significant mode degradation. Our results show that as this transition happens, a third peak (anomalous mode) becomes dominant. The amplitude and wavelength of this peak increase quadratically with the thickness of the Si layer, indicating formation of a unique collective mode. We study the impact of this mode on the emission semiconductor quantum dots, demonstrating they become much brighter as the result of the long-reach plasmonic fields of the nanodisks when the arrays are in this mode.

  1. Effect of Ti adhesive layer on individual gold nanodisk surface plasmon resonance

    Science.gov (United States)

    Debu, Desalegn Tadesse; Ghosh, Pijush; French, David; Bauman, Stephen; Herzog, Joseph B.

    We investigate localized surface plasmon resonance (SPR) of gold nanodisks of various diameter and height fabricated on extremely thin Ti adhesive layers. Dark field scattering measurements reveal significant dependence of SPR in the size nano structures and polarization of the light. Comparisons of peak resonance extracted from spectra using Gaussian fitting of different Ti adhesive layer thickness indicates significant red shifting and damping of the plasmon mode. Experimental results are supported by numerical simulation based on three dimensional finite element time domain analysis. From the simulation and experimental results we quantitatively developed optimized model equation of resonance mode of the nanodisks with respect to adhesive layer thickness and broadening effect of the line shape. Such optimized model is very helpful in guiding targeted nanofabrication such as gold nanodisk antennas or biosensors.

  2. Dynamic Tuning of Plasmon-Exciton Coupling in Arrays of Nanodisk-J-aggregate Complexes

    KAUST Repository

    Zheng, Yue Bing

    2010-07-21

    Figure Presented Dynamic tuning of plasmon-exclton resonant coupling in arrays of nanodisk-J-aggregate complexes is demonstrated. The angle-resolved spectra of an array of bare gold nanodisks exhibit continuous shifting of localized surface plasmon resonance. This characteristic enables the production of real-time, controllable spectral overlap between molecular resonance and plasmóme resonance. The resonant interaction strength as a function of spectral overlap is explored and the coupling strength changes with the incident angle of a probe light, in accord with simulations based on coupled dipóle approximation method. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Binary teaching-learning-based optimization algorithm is used to investigate the superscattering plasmonic nanodisk

    Science.gov (United States)

    Kaboli, M.; Akhlaghi, M.

    2016-06-01

    A new efficient binary optimization method based on Teaching-Learning-Based Optimization (TLBO) algorithm is proposed to design an array of plasmonic nanodisks in order to achieve maximum scattering coefficient spectrum. In binary TLBO (BTLBO), a group of learner consists of a matrix with binary entries; control the presence (`1') or the absence (`0') of nanodisks in the array. Simulation results show that scattering coefficient strongly depends on the localized position of nanoparticles and non-periodic structures have more appropriate response in term of scattering coefficient. This approach can be useful in optical applications such as plasmonic nanoantennas.

  4. Experimental evidence of skyrmion-like configurations in bilayer nanodisks with perpendicular magnetic anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    Stebliy, Maxim E., E-mail: stebliyme@gmail.com; Kolesnikov, Alexander G.; Davydenko, Alexander V.; Ognev, Alexey V.; Samardak, Alexander S.; Chebotkevich, Ludmila A. [Laboratory of Thin Film Technologies, School of Natural Sciences, Far Eastern Federal University, Vladivostok 690950 (Russian Federation)

    2015-05-07

    Formation and existence of magnetic skyrmion-like configurations in bilayer nanodisks (Ta(3 nm)/[Co(0.37 nm)/Ni(0.58 nm)]{sub 10}){sub 2} with perpendicular magnetic anisotropy are shown experimentally at room temperature. Magnetization reversal through the skyrmion state is studied using magnetic hysteresis measurements. An evolution of skyrmion configurations in the nanodisk structure is analyzed. Experimental methods and micromagnetic simulations help to understand the magnetization reversal processes occurring through the stable skyrmion-like configurations. Formation of the intermediate C-states during magnetization reversal is demonstrated. The skyrmion number for all possible spin configurations is calculated.

  5. Apolipoprotein E genotype in schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Joober, R.; Lal, S.; Bloom, D.; Benkelfat, C. [McGill Research Centre for Schizophrenia, Douglas Hospital, Montreal (Canada)] [and others

    1996-04-09

    We investigated the association between schizophrenia and the allelic polymorphism in the apolipoprotein E (Apo E) gene in 51 schizophrenic patients and 35 controls. The Apo E4 allele was equally represented in the schizophrenic group (16%) and the control group (20%) suggesting no association between schizophrenia and the Apo E4 allele. The apolipoprotein E (Apo E) is a polymorphic (E2, E3, and E4) lipoprotein involved in the transmembrane transport of cholesterol and is thought to play an important role in neuronal growth and in the central nervous system response to injury, particularly in the hippocampal region. Recent findings strongly suggest that the Apo E4 allele is associated with cognitive deficits in normal and pathological aging, e.g., Alzheimer`s disease. 5 refs., 1 tab.

  6. Apolipoprotein E and familial longevity

    DEFF Research Database (Denmark)

    Schupf, Nicole; Barral, Sandra; Perls, Thomas;

    2013-01-01

    Exceptional longevity is associated with substantial heritability. The ε4 allele in apolipoprotein E and the linked G allele in rs2075650 of TOMM40 have been associated with increased mortality and the ε2 allele with decreased mortality, although inconsistently. Offspring from long-lived families...... findings support the hypothesis that both reduction in the frequency of the ε4 allele and increase in the frequency of the ε2 allele contribute to longevity....

  7. Strain-tunable plasmonic crystal using elevated nanodisks with polarization-dependent characteristics

    Science.gov (United States)

    Wang, Yifei; Liu, Longju; Wang, Qiugu; Han, Weikun; Lu, Meng; Dong, Liang

    2016-02-01

    This paper reports on the mechanical tuning of optical resonances of a flexible plasmonic crystal. The device is structured with a square lattice nanopost array standing out of an elastomer substrate and coated with a gold thin film. The gold nanodisks residing on top of the nanoposts support a surface plasmon polariton (SPP) Bloch wave mode at the gold-air interface. By applying a strain along a planar direction of the substrate, the period of the elevated nanodisk array changes, thus altering the SPP resonance wavelength. Because the applied strain breaks period symmetry of the nanodisk array, the original single resonance mode is split into two polarized resonance modes. For the incident light polarized parallel with and perpendicular to the direction of the applied strain, the corresponding resonance modes are shifted in opposite directions at a rate of 1.6 ± 0.1 nm for every 1% change in strain. During stretching and compressing the substrate, the applied strains only change the period between nearby nanodisks without affecting their shape and morphology. This has improved reliability and repeatability of resonance tuning of the device.

  8. D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

    Science.gov (United States)

    Valleix, Sophie; Verona, Guglielmo; Jourde-Chiche, Noémie; Nédelec, Brigitte; Mangione, P. Patrizia; Bridoux, Frank; Mangé, Alain; Dogan, Ahmet; Goujon, Jean-Michel; Lhomme, Marie; Dauteuille, Carolane; Chabert, Michèle; Porcari, Riccardo; Waudby, Christopher A.; Relini, Annalisa; Talmud, Philippa J.; Kovrov, Oleg; Olivecrona, Gunilla; Stoppini, Monica; Christodoulou, John; Hawkins, Philip N.; Grateau, Gilles; Delpech, Marc; Kontush, Anatol; Gillmore, Julian D.; Kalopissis, Athina D.; Bellotti, Vittorio

    2016-01-01

    Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients. PMID:26790392

  9. D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile.

    Science.gov (United States)

    Valleix, Sophie; Verona, Guglielmo; Jourde-Chiche, Noémie; Nédelec, Brigitte; Mangione, P Patrizia; Bridoux, Frank; Mangé, Alain; Dogan, Ahmet; Goujon, Jean-Michel; Lhomme, Marie; Dauteuille, Carolane; Chabert, Michèle; Porcari, Riccardo; Waudby, Christopher A; Relini, Annalisa; Talmud, Philippa J; Kovrov, Oleg; Olivecrona, Gunilla; Stoppini, Monica; Christodoulou, John; Hawkins, Philip N; Grateau, Gilles; Delpech, Marc; Kontush, Anatol; Gillmore, Julian D; Kalopissis, Athina D; Bellotti, Vittorio

    2016-01-01

    Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients. PMID:26790392

  10. Role of apolipoprotein E in febrile convulsion.

    Science.gov (United States)

    Giray, Ozlem; Ulgenalp, Ayfer; Bora, Elçin; Uran, Nedret; Yilmaz, Ebru; Unalp, Aycan; Erçal, Derya

    2008-10-01

    Apolipoprotein E is consistently associated with the progression of some common human neurodegenerative diseases, e.g., epilepsy. We hypothesized that genetic variations in the apolipoprotein E gene have implications for susceptibility to, and prognoses in, febrile convulsion, which plays an apparent role in the development of epilepsy. We used the polymerase chain reaction and restriction enzyme digestion to characterize variations of the apolipoprotein E gene. Sixty-nine patients with febrile convulsion (simple/complex) and a corresponding cohort of healthy patients (n = 75) were used. There was no significant difference in genotypic distribution and allelic frequencies of the apolipoprotein E gene between the febrile convulsion and control groups. Comparing subpopulations of the febrile convulsion group (patients with simple and complex febrile convulsion), we noted that no patients with the epsilon3/epsilon4 genotype had complex febrile convulsions. The apolipoprotein E epsilon3/epsilon4 genotype was more frequently seen in the simple febrile than in the complicated febrile convulsion group (9 versus 0 patients, respectively). The data indicate an association with the epsilon3/epsilon4 genotype of the apolipoprotein E gene with a milder phenotype. Although apolipoprotein E4 is not a vulnerability factor regarding febrile convulsions, it seems effective in regard to prognoses. PMID:18805361

  11. Identification of apolipoprotein using feature selection technique.

    Science.gov (United States)

    Tang, Hua; Zou, Ping; Zhang, Chunmei; Chen, Rong; Chen, Wei; Lin, Hao

    2016-01-01

    Apolipoprotein is a kind of protein which can transport the lipids through the lymphatic and circulatory systems. The abnormal expression level of apolipoprotein always causes angiocardiopathy. Thus, correct recognition of apolipoprotein from proteomic data is very crucial to the comprehension of cardiovascular system and drug design. This study is to develop a computational model to predict apolipoproteins. In the model, the apolipoproteins and non-apolipoproteins were collected to form benchmark dataset. On the basis of the dataset, we extracted the g-gap dipeptide composition information from residue sequences to formulate protein samples. To exclude redundant information or noise, the analysis of various (ANOVA)-based feature selection technique was proposed to find out the best feature subset. The support vector machine (SVM) was selected as discrimination algorithm. Results show that 96.2% of sensitivity and 99.3% of specificity were achieved in five-fold cross-validation. These findings open new perspectives to improve apolipoproteins prediction by considering the specific dipeptides. We expect that these findings will help to improve drug development in anti-angiocardiopathy disease. PMID:27443605

  12. Interaction between magnetic vortex cores in a pair of nonidentical nanodisks

    International Nuclear Information System (INIS)

    The coupling of two nonidentical magnetic nanodisks, i.e., with different vortex gyrotropic frequencies, is studied. From the analytical approach, the interactions between the nanodisks along x and y directions (the coupling integrals) were obtained as a function of distance. From the numerical solution of Thiele's equation, we derived the eigenfrequencies of the vortex cores as a function of distance. The motion of the two vortex cores and, consequently, the time dependence of the total magnetization M(t) were derived both using Thiele's equation and by micromagnetic simulation. From M(t), a recently developed method, the magnetic vortex echoes, analogous to the Nuclear Magnetic Resonance spin echoes, was used to compute the distance dependence of the magnetic coupling strength. The results of the two approaches differ by approximately 10%; using one single term, a dependence with distance found is broadly in agreement with studies employing other techniques.

  13. Narrow band absorber based on a dielectric nanodisk array on silver film

    Science.gov (United States)

    Callewaert, F.; Chen, S.; Butun, S.; Aydin, K.

    2016-07-01

    The simulations of normally incident visible light absorption in a periodic array of dielectric nanodisks on the top of a silver film are presented. Electromagnetic simulations indicate narrow resonances with absorption intensities as large as 95%. The absorption enhancement due to the periodic array can be as high as a factor of 30 compared to an equivalent dielectric film on top of a silver mirror. A parametric study shows that the resonance characteristics and the number of modes can be easily tuned and controlled by the refractive index and the geometric parameters of the nanodisks. In particular, the structure can be tuned to have either a single or two absorption peaks. The characteristics of the two main resonance peaks are described in detail using the simulated electric field profiles and the dispersion relation. Proposed narrowband absorber design utilizing continuous metal films and nanostructured dielectric arrays could be used for narrow-band absorption filters, refractive-index based biosensing applications and thermal emitters.

  14. Chirality selection in the vortex state of magnetic nanodisks with a screw dislocation

    Directory of Open Access Journals (Sweden)

    Rößler U. K.

    2013-01-01

    Full Text Available Structural defects in magnetic crystalline materials may locally change magnetic properties and can significantly influence the behavior of magnetic nanostructures. E.g., surface-induced Dzyaloshinskii-Moriya interactions can strongly affect vortex structures in magnetic nanodisks causing a chirality selection. Near lattice defects, the spin-orbit interactions induce local antisymmetric Dzyaloshinskii-Moriya exchange and cause effective anisotropies, which can result in spin canting. Broken inversion symmetry near a defect leads to locally chiral exchange. We present a phenomenological approach for dislocation-induced Dzyaloshinskii-Moriya couplings. As an example we investigate effects of a screw dislocation at the center of a magnetic nanodisk with a vortex state. By numerical calculations on vortex profiles we analyze equilibrium parameters of the vortex as functions of applied magnetic field and the material and geometrical parameters. It is proposed that magnetic nanodisks with defects provide a suitable experimental setting to study induced chirality by spin-orbit effects.

  15. Elasto-dynamic analysis of spinning nanodisks via a surface energy-based model

    Science.gov (United States)

    Kiani, Keivan

    2016-07-01

    Using the surface elasticity theory of Gurtin and Murdoch, in-plane vibrations of annular nanodisks due to their rotary motion are explored. By the imposition of non-classical boundary conditions on the innermost and outermost surfaces and employing Hamilton’s principle, the unknown elasto-dynamic fields of the bulk zone are determined via the finite element method. The roles of both nanodisk geometry and surface effect on the natural frequencies are addressed. Subsequently, forced vibrations of spinning nanodisks with fixed–free and free–free boundary conditions are comprehensively examined. The obtained results show that the maximum dynamic elastic fields grow in a parabolic manner as the steady angular velocity increases. By increasing the outermost radius, the maximum dynamic elastic field is magnified and the influence of the surface effect on the results reduced. This work can be considered as a pivotal step towards optimal design and dynamic analysis of nanorotors with disk-like parts, which are one of the basic building blocks of the upcoming advanced nanotechnologies.

  16. Dynamically tunable Fano resonance in planar structures based on periodically asymmetric graphene nanodisk pair

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhengren [School of Science, Chongqing Jiaotong University, Chongqing 400074 (China); Su, Xiaopeng [Department of Physics, Tongji University, Shanghai 200092 (China); Fan, Yuancheng [Key Laboratory of Space Applied Physics and Chemistry, Ministry of Education and Department of Applied Physics, School of Science, Northwestern Polytechnical University, Xi' an 710129 (China); Yin, Pengfei [School of Science, Chongqing Jiaotong University, Chongqing 400074 (China); Zhang, Liwei [School of Physics and Chemistry, Henan Polytechnic University, Jiaozuo 454000 (China); Shi, Xi, E-mail: xishi@tongji.edu.cn [Department of Physics, Tongji University, Shanghai 200092 (China)

    2015-09-15

    We present a dynamically frequency tunable Fano resonance planar device composed of periodically asymmetric graphene nanodisk pair for the mid-infrared region. The two asymmetric graphene nanodisks can be directly excited by the light simultaneously and produce two kinds of reflected light with almost the same spectrum linewidth. By studying the local field distributions of our structure, we find that there are two kinds of modes for the two asymmetric graphene nanodisks, i.e., the symmetric mode and antisymmetric mode. Resonance coupling between the symmetric and antisymmetric modes generates the Fano resonance in our structure. This Fano resonance generation mechanism is different from it in traditional Fano resonance structure. In the traditional Fano resonance structure, the Fano resonance comes from the coupling effect between continuum and discrete structure. Moreover, we find that both of the Fano resonance amplitude and frequency of the structure can be dynamically controlled by varying the Fermi energy of graphene. Resonance transition in the structure is studied to reveal the physical mechanism behind it.

  17. Comparison of Carbohydrate Compositions of Total Apolipoproteins in Lipoproteins

    OpenAIRE

    Güldür, Tayfun; OZAN, Sema; İLERİ, Tülay

    1998-01-01

    Terminal carbohydrate moieties of apolipoproteins of lipoproteins in human and goat serum were ascertained and compared. Apolipoproteins of b+pre-b (apolipoprotein B containing lipoproteins) and a lipoproteins separated by phosphotungstic acid/MgCl2 precipitation method were applied to SDS-PAGE and blotted onto nitrocellulose membrane. Digoxigenin labelled lectins, each of which recognizes a specific sugar sequence, were incubated with apolipoproteins immobilized on a western blot membrane to...

  18. Moessbauer spectroscopy and magnetization of ordered arrays of ultrathin FePt nanodisks with perpendicular magnetisation

    Energy Technology Data Exchange (ETDEWEB)

    Ellrich, J., E-mail: jens.ellrich@grenzebach.com; Kruk, R., E-mail: robert.kruk@kit.edu; Brand, R. A., E-mail: richard.brand@kit.edu; Hahn, H., E-mail: horst.hahn@kit.edu [Karlsruhe Institute of Technology, Institute for Nanotechnology (Germany); Huetten, A., E-mail: huetten@physik.uni-bielefeld.de [Bielefeld University, Department of Physics, Physics of Nanostructures (Germany); Lei, Y., E-mail: yong.lei@tu-ilmenau.de [Technische Universitaet Ilmenau, Fachgebiet 3D-Nanostrukturierung Institut fuer Physik and IMN (Germany)

    2012-05-15

    The purpose of this communication is to show that arrays of FePt with perpendicular anisotropy can be studied using energy-selective conversion electron Moessbauer spectroscopy. Magnetic nanostructures have been in the focus of technology and science for many years. One of the economically and comparably scientifically most demanding application of these structures is in storage devices such as hard-disks and MRAMs. The FePt nanodisks presented here show a combination of material and magnetic properties which enable the fabrication of highly ordered nanostructures.

  19. Surface sensitivity of optical and magneto-optical and ellipsometric properties in magnetoplasmonic nanodisks

    Science.gov (United States)

    Herreño-Fierro, César A.; Patiño, Edgar J.; Armelles, Gaspar; Cebollada, Alfonso

    2016-01-01

    The optical, ellipsometric, and magneto-optical surface sensitivity to dielectric environment of magnetoplasmonic nanodisks is experimentally studied. Here, the shift of the corresponding spectral structures as a function of the thickness of a coating SiO2 layer is characterized. Our results reveal that the so called pseudo-Brewster Angle, easily identified in the ellipsometric phase (Δ) spectrum, is up to four times more sensitive than the conventional features used in surface plasmon resonance based sensors. These results highlight the need of investigating the factual implementation of this technique to develop improved ellipsometric-phase based transducers for bio-chemical sensing purposes.

  20. Surface sensitivity to dielectric environment of optical and magneto-optical properties in magnetoplasmonic nanodisks

    Science.gov (United States)

    Herreño-Fierro, César Aurelio; Patino, Edgar J.; Armelles, Gaspar; Cebollada, Alfonso

    The optical, ellipsometric and magneto-optical surface sensitivity to dielectric environment of magnetoplasmonic nanodisks is experimentally studied. Here the shift of the corresponding spectral structures as a function of the thickness of a coating SiO2 layer is characterized. Our results reveal that the so called pseudo-Brewster Angle, easily identified in the ellipsometric phase (Δ) spectrum, is up to four times more sensitive than the conventional features used in Surface Plasmon Resonance (SPR) based sensors. These results highlight the need of investigating the factual implementation of this technique to develop improved ellipsometric-phase based transducers for bio-chemical sensing purposes. Email: caherrenof@udistrital.edu.co.

  1. Numerical studies on antiferromagnetic skyrmions in nanodisks by means of a new quantum simulation approach

    Science.gov (United States)

    Liu, Zhaosen; Ian, Hou

    2016-04-01

    We employ a new quantum simulation approach to study the magnetism of nanodisks with Dzyaloshinsky-Moriya (DM) interaction. We find that a weak external magnetic field normal to the disk plane cannot obviously affect the single AFM skyrmion structure on small disk; but if it is sufficiently strong, it can destroy the AFM skyrmion completely. By increasing DM interaction, more self-organized magnetic domains appear, the average distance of the neighboring domains agrees well with a grid theory. In this case, a magnetic anisotropy normal to the disk plane can re-construct AFM skyrmion, providing a way for experimentalists to create AMF skyrmions.

  2. How much better are InGaN/GaN nanodisks than quantum wells—Oscillator strength enhancement and changes in optical properties

    International Nuclear Information System (INIS)

    We show over 100-fold enhancement of the exciton oscillator strength as the diameter of an InGaN nanodisk in a GaN nanopillar is reduced from a few micrometers to less than 40 nm, corresponding to the quantum dot limit. The enhancement results from significant strain relaxation in nanodisks less than 100 nm in diameter. Meanwhile, the radiative decay rate is only improved by 10 folds due to strong reduction of the local density of photon states in small nanodisks. Further increase in the radiative decay rate can be achieved by engineering the local density of photon states, such as adding a dielectric coating

  3. Silica nanodisks as platforms for fluorescence lifetime-based sensing of pH

    Indian Academy of Sciences (India)

    Subhasree Banerjee; Anjali Dhir; Tuseeta Banerjee; Avinash Kumar Singh; Anindya Datta

    2011-11-01

    Core-shell conjugates of silica nanodisks and fluorescent dyes have been prepared. Rhodamine B, the reference, has been attached to the core, by surface functionalization of the pristine SNDs. Then, a layer of silica has been deposited on the composite nanodisks. Finally, the surface has been functionalized with fluorescein in one case and protoporphyrin IX in the other. These dyes exhibit pH-dependent fluorescence properties. The nanoconjugates are found to sense the pH of the medium, through systematic variation of the fluorescence intensity ratios of the reporter dye at the surface and the reference dye at the core. Moreover, the fluorescence lifetimes and corresponding amplitudes of the reporter dyes have been found to be reliable parameters for assessing the pH of the medium, even though the variation in lifetimes of fluorescein is rather small. In case of protoporphyrin, however, this variation is significantly large. Besides, the change in amplitudes is prominent in acidic as well as alkaline solutions. The temporal parameters can thus be used to ascertain the pH of the medium, when used in conjunction with each other.

  4. Plasmonic Fano interference produced by gold nano-disks on a dielectric Bragg stack

    Science.gov (United States)

    Hajebifard, Akram; Berini, Pierre

    2015-09-01

    Fano interference is predicted in a structure consisting of a periodic array of uncoupled gold nano-disks (AuNDs) supported by a Bragg stack. The phenomenon occurs due to resonant interference between the reflection spectrum of the Bragg stack and localized surface plasmon resonances (LSPRs) on the AuNDs. Fitting the computational results to the Fano lineshape formula yields the Fano parameters of the resonances including their linewidth. One of the most important advantages of the structure is that the linewidth of the Fano resonances (˜9 nm) is much narrower than the bandwidth of the LSPR nano-disks (˜80 nm) and the reflection bandwidth of the Bragg stack on which the disks are supported (˜100 nm). The narrow Fano linewidth and the ease with which they can be interrogated using perpendicularly incident light makes the structure attractive for biosensing applications. The bulk sensitivities and figure of merit of Fano resonances in a proposed design are 44 nm/RIU (redshift) and -52 nm/RIU (blueshift), and ˜4 RIU-1, respectively.

  5. From Fano-like interference to superscattering with a single metallic nanodisk.

    Science.gov (United States)

    Wan, Weiwei; Zheng, Wenwei; Chen, Yanfeng; Liu, Zhaowei

    2014-08-01

    Superscattering was theoretically proposed to significantly enhance the scattering cross-section of a subwavelength nanostructure, far exceeding its single-resonance limit by employing resonances of multiple plasmonic modes. By numerical simulation, we design a subwavelength nanodisk as a simple candidate to achieve superscattering. Due to the phase retardation, the subradiant mode can be excited and interact with the superradiant mode in both spatial and frequency domains. By changing the height and diameter of the nanodisk, we show high tunability of the mode interaction and evolution of the resulting spectral features from Fano-like resonance to superscattering. A model of two-driven coupled oscillators is proposed to quantitatively analyze the spectral evolution. We find that the evolution is caused by not only alignment of the resonant wavelengths of related plasmonic modes, but also reasonably high loss. We show that superscattering doubles the near-field intensity, potentially enhancing the signal 16 times for SERS and 4 times for SEIRS, and doubles the far-field intensity and decreases the peak linewidth, improving the figure of merit for plasmonic refractometric sensing. Our study provides quantitative physical insight into understanding superscattering and Fano-like resonances in a single nanoparticle. PMID:24975582

  6. Enhanced Third Harmonic Generation in Single Germanium Nanodisks Excited at the Anapole Mode.

    Science.gov (United States)

    Grinblat, Gustavo; Li, Yi; Nielsen, Michael P; Oulton, Rupert F; Maier, Stefan A

    2016-07-13

    We present an all-dielectric germanium nanosystem exhibiting a strong third order nonlinear response and efficient third harmonic generation in the optical regime. A thin germanium nanodisk shows a pronounced valley in its scattering cross section at the dark anapole mode, while the electric field energy inside the disk is maximized due to high confinement within the dielectric. We investigate the dependence of the third harmonic signal on disk size and pump wavelength to reveal the nature of the anapole mode. Each germanium nanodisk generates a high effective third order susceptibility of χ((3)) = 4.3 × 10(-9) esu, corresponding to an associated third harmonic conversion efficiency of 0.0001% at an excitation wavelength of 1650 nm, which is 4 orders of magnitude greater than the case of an unstructured germanium reference film. Furthermore, the nonlinear conversion via the anapole mode outperforms that via the radiative dipolar resonances by about 1 order of magnitude, which is consistent with our numerical simulations. These findings open new possibilities for the optimization of upconversion processes on the nanoscale through the appropriate engineering of suitable dielectric materials. PMID:27331867

  7. Apolipoprotein M - a new biomarker in sepsis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2012-01-01

    Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship to...

  8. Low Temperature Hydrothermal Synthesis of ZnO Nanodisk Arrays Utilizing Self-assembly of Surfactant Molecules at Solid-liquid Interfaces

    International Nuclear Information System (INIS)

    ZnO nanodisk arrays have been prepared by utilizing cooperative surface assembly of surfactants and inorganic species at the solid-liquid interfaces under the mild condition. Photoluminescence measurement showed that the obtained ZnO nanodisk arrays exhibit new optical property comparing to the previous results of diverse ZnO nanostructures. Such nanostructures are expected to find more applications employing their optical and electrical properties

  9. All-Optical Modulation of Localized Surface Plasmon Coupling in a Hybrid System Composed of Photo-Switchable Gratings and Au Nanodisk Arrays

    OpenAIRE

    Liu, Yan Jun; Zheng, Yue Bing; Liou, Justin; Chiang, I-Kao; Khoo, Iam Choon; Huang, Tony Jun

    2011-01-01

    We conduct a real-time study of all-optical modulation of localized surface plasmon resonance (LSPR) coupling in a hybrid system that integrates a photo-switchable optical grating with a gold nanodisk array. This hybrid system enables us to investigate two important interactions: 1) LSPR-enhanced grating diffraction, and 2) diffraction-mediated LSPR in the Au nanodisk array. The physical mechanism underlying these interactions was analyzed and experimentally confirmed. With its advantages in ...

  10. Effects of Dzyaloshinsky–Moriya interaction on magnetism in nanodisks from a self-consistent approach

    International Nuclear Information System (INIS)

    We give a theoretical study on the magnetic properties of monolayer nanodisks with both Heisenberg exchange and Dzyaloshinsky–Moriya (DM) interactions. In particular, we survey the magnetic effects caused by anisotropy, external magnetic field, and disk size when DM interaction is present by means of a new quantum simulation method facilitated by a self-consistent algorithm based on mean field theory. This computational approach finds that uniaxial anisotropy and transversal magnetic field enhance the net magnetization as well as increase the transition temperature of the vortical phase while preserving the chiralities of the swirly magnetic structures, whereas when the strength of DM interaction is sufficiently strong for a given disk size, magnetic domains appear within the circularly bounded region, which vanish and give in to a single vortex when a transversal magnetic field is applied. The latter confirms the magnetic skyrmions induced by the magnetic field as observed in the experiments

  11. Effects of Dzyaloshinsky–Moriya interaction on magnetism in nanodisks from a self-consistent approach

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhaosen, E-mail: liuzhsnj@yahoo.com [Nanjing University of Information Science and Technology, Department of Applied Physics (China); Ian, Hou, E-mail: houian@umac.mo [University of Macau, Institute of Applied Physics and Materials Engineering, FST (China)

    2016-01-15

    We give a theoretical study on the magnetic properties of monolayer nanodisks with both Heisenberg exchange and Dzyaloshinsky–Moriya (DM) interactions. In particular, we survey the magnetic effects caused by anisotropy, external magnetic field, and disk size when DM interaction is present by means of a new quantum simulation method facilitated by a self-consistent algorithm based on mean field theory. This computational approach finds that uniaxial anisotropy and transversal magnetic field enhance the net magnetization as well as increase the transition temperature of the vortical phase while preserving the chiralities of the swirly magnetic structures, whereas when the strength of DM interaction is sufficiently strong for a given disk size, magnetic domains appear within the circularly bounded region, which vanish and give in to a single vortex when a transversal magnetic field is applied. The latter confirms the magnetic skyrmions induced by the magnetic field as observed in the experiments.

  12. Giant magnetism in punched zigzag-edged triangular-shaped graphene nanodisks

    Energy Technology Data Exchange (ETDEWEB)

    Agrawal, Bal K., E-mail: balkagl@rediffmail.com, E-mail: balkagr@yahoomail.com; Agrawal, S. [University of Allahabad, Department of Physics (India)

    2015-01-15

    We observe, for the first time, a very large magnetism in the nano-sized (7–27 Å) punched graphene nanodisks (PGNDs) i.e., zigzag-edged triangular PGNDs (ZET-PGNDs). A first-principles method has been employed to investigate their electronic and magnetic properties. Similar to a regular or unpunched ZET-GND where the spin value scales with the linear dimension of the ZET-GND arising from the topological frustration of the π bonds and the induced spin distributions in graphene structures, the magnetic moment in a PGND increases with its size very rapidly depending on the type of punching. Two types of the punched nanodisks have been discussed. In one type of PGND, the magnetic moment of the punched out smaller GND is added to the magnetic moment of the host GND and the resultant net magnetism is, thus, equal to the sum of the magnetic moments of the host GND and that of the punched out smaller GND. In the other type of the PGND, the magnetic moment of the punched out smaller GND is subtracted from the magnetic moment of the host GND and the net value of the magnetic moment is the difference of the magnetic moments of the host GND and that of the punched out smaller GND. One may, thus, enhance the magnetism of a GND by making an appropriate choice of the punching. It may have large magnetic moments in the passivated ZET-PGNDs beyond the nanoscale at room temperature. These punched graphene fragments may be employed for the preparation of several kinds of the electronic and spintronic devices possessing exotic features.

  13. Apolipoprotein E Polymorphism in Tuberculosis Patients

    Science.gov (United States)

    Naserpour Farivar, Taghi; Sharifi Moud, Batool; Sargazi, Mansur; Moeenrezakhanlou, Alireza

    In this study, we aimed to determine the significance of association between Tuberculosis and apolipoprotein E polymorphism. The apolipoprotein E genotypes were assayed in 250 tuberculosis patients by polymerase chain reaction followed by enzymatic digestion with Hha I. The results were compared with the results of the same experiments on 250 sex and age matched control peoples. Present results showed that in studied populations, prevalence of E4 genotype was lower in controls than in patients (8 v. 13.2%; OR = 1.75, pStatistically significant difference was found between patients and controls with respect to ɛ2 allele frequencies, while ɛ2 allele frequency was found to be much less prevalent in controls (6%) than in patients (35.8%; OR = 8.72, p<0.05). Also, our study revealed that there is an association between apolipoprotein E genotypes and amplitude to tuberculosis in studied populations. However, large population-based studies are needed to understand the exact role played by the locus in causing the condition.

  14. Apolipoprotein E mimetic peptide protects against diffuse brain injur y

    Institute of Scientific and Technical Information of China (English)

    Yaning Zhao; Jianmin Li; Qiqun Tang; Junling Gao; Changxiang Chen; Liwei Jing; Pan Zhang; Shuxing Li

    2014-01-01

    Apolipoprotein E plays a crucial role in inhibiting chronic neurodegenerative processes. Howev-er, its impact on neurological function following diffuse brain injury is still unclear. This study was designed to evaluate the therapeutic effects and mechanisms of action of apolipoprotein E mimetic peptide on diffuse brain injury. Apolipoprotein E mimetic peptide was administered into the caudal vein of rats with diffuse brain injury before and after injury. We found that apo-lipoprotein E mimetic peptide signiifcantly decreased the number of apoptotic neurons, reduced extracellular signal-regulated kinase1/2 phosphorylation, down-regulated Bax and cytochrome c expression, decreased malondialdehyde content, and increased superoxide dismutase activity in a dose-dependent manner. These experimental ifndings demonstrate that apolipoprotein E mimetic peptide improves learning and memory function and protects against diffuse brain injury-induced apoptosis by inhibiting the extracellular signal-regulated kinase1/2-Bax mito-chondrial apoptotic pathway.

  15. Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Bo Li

    Full Text Available Although there is evidence that visfatin is associated with atherogenesis, the effect of visfatin on plaque stability has not yet been explored.In vivo, vulnerable plaques were established by carotid collar placement in apolipoprotein E-deficient (ApoE-/- mice, and lentivirus expressing visfatin (lenti-visfatin was locally infused in the carotid artery. The lipid, macrophage, smooth muscle cell (SMC and collagen levels were evaluated, and the vulnerability index was calculated. In vitro, RAW264.7 cells were stimulated with visfatin, and the MMPs expressions were assessed by western blot and immunofluorescence. And the mechanism that involved in visfatin-induced MMP-8 production was investigated.Transfection with lenti-visfatin significantly promoted the expression of visfatin which mainly expressed in macrophages in the plaque. Lenti-visfatin transfection significantly promoted the accumulation of lipids and macrophages, modulated the phenotypes of smooth muscle cells and decreased the collagen levels in the plaques, which significantly decreased the plaque stability. Simultaneously, transfection with lenti-visfatin significantly up-regulated the expression of MMP-8 in vivo, as well as MMP-1, MMP-2 and MMP-9. Recombinant visfatin dose- and time-dependently up-regulated the in vitro expression of MMP-8 in macrophages. Visfatin promoted the translocation of NF-κB, and inhibition of NF-κB significantly reduced visfatin-induced MMP-8 production.Visfatin increased MMP-8 expression, promoted collagen degradation and increased the plaques vulnerability index.

  16. Apolipoproteins, lipids and risk of cancer.

    Science.gov (United States)

    Borgquist, Signe; Butt, Talha; Almgren, Peter; Shiffman, Dov; Stocks, Tanja; Orho-Melander, Marju; Manjer, Jonas; Melander, Olle

    2016-06-01

    The epidemiological evidence for an obesity-cancer association is solid, whereas the association between obesity-associated lipoprotein levels and cancer is less evident. We investigated circulating levels of Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) and association to risk of overall cancer and common cancer forms. The Malmö Diet and Cancer Study, a population-based prospective cohort study, enrolled 17,035 women and 11,063 men (1991-1996). Incident cancer cases were ascertained by record linkage with the Swedish Cancer Registry until end of follow-up, January 1, 2012. Baseline serum levels of ApoA1 and ApoB were analyzed for the entire cohort and HDL-C and LDL-C levels in 5,281 participants. Hazard ratios, with 95% confidence interval, were calculated using Cox's proportional hazards analysis. In the entire cohort, none of the exposures were related to overall cancer risk (HRadj ApoA1 = 0.98, 95%CI: 0.95,1.01; HRadj ApoB = 1.01, 95%CI: 0.98-1.04). Among men, ApoB was positively associated with cancer risk (HRadj ApoB = 1.06, 95%CI: 1.01,1.10). Female breast cancer risk was inversely associated with ApoB (HRadj = 0.92, 95%CI: 0.86,0.99). Among both genders, ApoA1 was inversely associated with lung cancer risk (HRadj = 0.88, 95%CI: 0.80,0.97), whereas high ApoB increased lung cancer risk (HRadj = 1.08, 95%CI: 0.99,1.18). Colorectal cancer risk was increased with high ApoB (HRadj = 1.08, 95%CI: 1.01,1.16) among both genders. Apolipoprotein levels were not associated with prostate cancer incidence. Circulating levels of apolipoproteins are associated with overall cancer risk in men and across both genders with breast, lung and colorectal cancer risk. Validation of these findings may facilitate future primary prevention strategies for cancer. PMID:26804063

  17. Apical secretion of apolipoproteins from enterocytes

    DEFF Research Database (Denmark)

    Danielsen, E M; Hansen, Gert Helge; Poulsen, Mona Dam

    1993-01-01

    soluble fraction, suggesting a basolateral secretion into the intercellular space, and both this accumulation and the release to the medium was prevented by culture at 20 degrees C. The specific radioactivity of apo A-1 and apo B-48 released to the medium was significantly higher than that of the...... corresponding apolipoproteins remaining associated with the intestinal tissue. Furthermore, during culture periods of up to 5 h, the enterocytes and their tight junctions largely remained intact as evidenced by the inaccessibility of the nonpermeable surface marker Ruthenium red. We therefore propose that...

  18. Statistical Behavior of Formation Process of Magnetic Vortex State in Ni80Fe20 Nanodisks

    Energy Technology Data Exchange (ETDEWEB)

    Im, Mi-Young; Fischer, Peter; Keisuke, Yamada; Kasai, Shinya

    2011-01-14

    Magnetic vortices in magnetic nanodots, which are characterized by an in-plane (chirality) and an out-of-plane (polarity) magnetizations, have been intensively attracted because of their high potential for technological application to data storage and memory scheme as well as their scientific interest for an understanding of fundamental physics in magnetic nanostructures. Complete understanding of the formation process of vortex state in magnetic vortex systems is very significant issue to achieve storage and memory technologies using magnetic vortices and understand intrinsic physical properties in magnetic nanostructures. In our work, we have statistically investigated the formation process of vortex state in permalloy (Py, Ni{sub 80}Fe{sub 20}) nanodisks through the direct observation of vortex structure utilizing a magnetic transmission soft X-ray microscopy (MTXM) with a high spatial resolution down to 20 nm. Magnetic imaging in Py nanodots was performed at the Fe L{sub 3} (707 eV) absorption edge. Figure 1 shows in-plane and out-of-plane magnetic components observed in 40 nm thick nanodot arrays with different dot radius of r = 500 and 400 nm, respectively. Vortex chirality, either clockwise (CW) or counter-clockwise (CCW), and polarity, either up or down, are clearly visible in both arrays. To investigate the statistical behavior in formation process of the vortex state, the observation of vortex structure at a remanant state after saturation of nanodots by an external magnetic field of 1 kOe has been repeatedly performed over 100 times for each array. The typical MTXM images of vortex chirality taken in two successive measurements together with their overlapped images in nanodot arrays of r = 500 and 400 nm are displayed in Fig. 2. Within the statistical measurement, the formation process of chirality of either CW or CCW is quite stochastic in each nanodot. Similar behavior is also witnessed in the formation of vortex polarity observed in consecutive

  19. Cloning and characterization of an apolipoprotein C2 promoter in the mouse central nervous system

    Institute of Scientific and Technical Information of China (English)

    Zhaoyang Li; Bing Du; Shengyang Li; Xiangchuan Lv; Shenglai Zhou; Yang Yu; Wei Wang; Zhihong Zheng

    2013-01-01

    Apolipoprotein C2 is an important member of the apolipoprotein C family, and is a potent activator of lipoprotein lipase. In the central nervous system, apolipoprotein C2 plays an important role in the catabolism of triglyceride-rich lipoproteins. Studies into the exact regulatory mechanism of mouse apolipoprotein C2 expression have not been reported. In this study, seven luciferase expression vectors, which contained potential mouse apolipoprotein C2 gene promoters, were constructed and co-transfected with pRL-TK into HEK293T cells to investigate apolipoprotein C2 promoter activity. Luciferase assays indicated that the apolipoprotein C2 promoter region was mainly located in the +104 bp to +470 bp region. The activity of the different lengths of apolipoprotein C2 promoter region varied. This staggered negative-positive-negative arrangement indicates the complex regulation of apolipoprotein C2 expression and provides important clues for elucidating the regulatory mechanism of apolipoprotein C2 gene transcription.

  20. On the impact of indium distribution on the electronic properties in InGaN nanodisks

    KAUST Repository

    Benaissa, M.

    2015-03-09

    We analyze an epitaxially grown heterostructure composed of InGaN nanodisks inserted in GaN nanowires in order to relate indium concentration to the electronic properties. This study was achieved with spatially resolved low-loss electron energy-loss spectroscopy using monochromated electrons to probe optical excitations - plasmons - at nanometer scale. Our findings show that each nanowire has its own indium fluctuation and therefore its own average composition. Due to this indium distribution, a scatter is obtained in plasmon energies, and therefore in the optical dielectric function, of the nanowire ensemble. We suppose that these inhomogeneous electronic properties significantly alter band-to-band transitions and consequently induce emission broadening. In addition, the observation of tailing indium composition into the GaN barrier suggests a graded well-barrier interface leading to further inhomogeneous broadening of the electro-optical properties. An improvement in the indium incorporation during growth is therefore needed to narrow the emission linewidth of the presently studied heterostructures.

  1. On the impact of indium distribution on the electronic properties in InGaN nanodisks

    Energy Technology Data Exchange (ETDEWEB)

    Benaissa, M., E-mail: benaissa.um5@gmail.com, E-mail: benaissa@fsr.ac.ma [LMPHE, Physics Department, Faculté des Sciences, Université Mohammed V, 4 Avenue Ibn Batouta, B.P. 1014 RP, 10000 Rabat (Morocco); Sigle, W.; Aken, P. A. van [Max Planck Institute for Intelligent Systems, Heisenbergstraße 3, 70569 Stuttgart (Germany); Ng, T. K.; Ooi, B. S. [Photonics Laboratory, King Abdullah University of Science and Technology, Thuwal 23955-6900 (Saudi Arabia); El Bouayadi, R. [LPMR, Université Mohammed Premier, B.P. 717, 60000 Oujda (Morocco); Jahangir, S.; Bhattacharya, P. [Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan 48109-2122 (United States)

    2015-03-09

    We analyze an epitaxially grown heterostructure composed of InGaN nanodisks inserted in GaN nanowires in order to relate indium concentration to the electronic properties. This study was achieved with spatially resolved low-loss electron energy-loss spectroscopy using monochromated electrons to probe optical excitations—plasmons—at nanometer scale. Our findings show that each nanowire has its own indium fluctuation and therefore its own average composition. Due to this indium distribution, a scatter is obtained in plasmon energies, and therefore in the optical dielectric function, of the nanowire ensemble. We suppose that these inhomogeneous electronic properties significantly alter band-to-band transitions and consequently induce emission broadening. In addition, the observation of tailing indium composition into the GaN barrier suggests a graded well-barrier interface leading to further inhomogeneous broadening of the electro-optical properties. An improvement in the indium incorporation during growth is therefore needed to narrow the emission linewidth of the presently studied heterostructures.

  2. All-Optical Modulation of Localized Surface Plasmon Coupling in a Hybrid System Composed of Photo-Switchable Gratings and Au Nanodisk Arrays

    Science.gov (United States)

    Liu, Yan Jun; Zheng, Yue Bing; Liou, Justin; Chiang, I-Kao; Khoo, Iam Choon; Huang, Tony Jun

    2011-01-01

    We conduct a real-time study of all-optical modulation of localized surface plasmon resonance (LSPR) coupling in a hybrid system that integrates a photo-switchable optical grating with a gold nanodisk array. This hybrid system enables us to investigate two important interactions: 1) LSPR-enhanced grating diffraction, and 2) diffraction-mediated LSPR in the Au nanodisk array. The physical mechanism underlying these interactions was analyzed and experimentally confirmed. With its advantages in cost-effective fabrication, easy integration, and all-optical control, the hybrid system described in this work could be valuable in many nanophotonic applications. PMID:21643480

  3. Silicon nanodisk array with a fin field-effect transistor for time-domain weighted sum calculation toward massively parallel spiking neural networks

    Science.gov (United States)

    Tohara, Takashi; Liang, Haichao; Tanaka, Hirofumi; Igarashi, Makoto; Samukawa, Seiji; Endo, Kazuhiko; Takahashi, Yasuo; Morie, Takashi

    2016-03-01

    A nanodisk array connected with a fin field-effect transistor is fabricated and analyzed for spiking neural network applications. This nanodevice performs weighted sums in the time domain using rising slopes of responses triggered by input spike pulses. The nanodisk arrays, which act as a resistance of several giga-ohms, are fabricated using a self-assembly bio-nano-template technique. Weighted sums are achieved with an energy dissipation on the order of 1 fJ, where the number of inputs can be more than one hundred. This amount of energy is several orders of magnitude lower than that of conventional digital processors.

  4. Independent effects of apolipoprotein AV and apolipoprotein CIII on plasma triglyceride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Baroukh, Nadine N.; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.

    2003-08-15

    Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered triglycerides. To overcome these confounding factors and address their relationship, we generated independent lines of mice that either over-expressed (''double transgenic'') or completely lacked (''double knockout'') both apolipoprotein genes. We report that both ''double transgenic'' and ''double knockout'' mice display intermedia tetriglyceride concentrations compared to over-expression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the ''double transgenic'' mice are approximately 500-fold lower than human ApoCIII levels, supporting Apo

  5. Stabilization

    Directory of Open Access Journals (Sweden)

    Muhammad H. Al-Malack

    2016-07-01

    Full Text Available Fuel oil flyash (FFA produced in power and water desalination plants firing crude oils in the Kingdom of Saudi Arabia is being disposed in landfills, which increases the burden on the environment, therefore, FFA utilization must be encouraged. In the current research, the effect of adding FFA on the engineering properties of two indigenous soils, namely sand and marl, was investigated. FFA was added at concentrations of 5%, 10% and 15% to both soils with and without the addition of Portland cement. Mixtures of the stabilized soils were thoroughly evaluated using compaction, California Bearing Ratio (CBR, unconfined compressive strength (USC and durability tests. Results of these tests indicated that stabilized sand mixtures could not attain the ACI strength requirements. However, marl was found to satisfy the ACI strength requirement when only 5% of FFA was added together with 5% of cement. When the FFA was increased to 10% and 15%, the mixture’s strength was found to decrease to values below the ACI requirements. Results of the Toxicity Characteristics Leaching Procedure (TCLP, which was performed on samples that passed the ACI requirements, indicated that FFA must be cautiously used in soil stabilization.

  6. Mössbauer spectroscopy and magnetization of ordered arrays of ultrathin FePt nanodisks with perpendicular magnetisation

    International Nuclear Information System (INIS)

    The purpose of this communication is to show that arrays of FePt with perpendicular anisotropy can be studied using energy-selective conversion electron Mössbauer spectroscopy. Magnetic nanostructures have been in the focus of technology and science for many years. One of the economically and comparably scientifically most demanding application of these structures is in storage devices such as hard-disks and MRAMs. The FePt nanodisks presented here show a combination of material and magnetic properties which enable the fabrication of highly ordered nanostructures.

  7. Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

    DEFF Research Database (Denmark)

    Elsøe, Sara; Christoffersen, Christina; Luchoomun, Jayraz;

    2013-01-01

    The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice.......The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice....

  8. Resolving the Relationship between Apolipoprotein E and Depression

    OpenAIRE

    Slifer, Michael A; Martin, Eden R.; Gilbert, John R.; Haines, Jonathan L.; Pericak-Vance, Margaret A.

    2009-01-01

    Several studies have reported an association between the ApolipoproteinE-ε4 (APOE4) allele and depression among elders. However others have failed to find an association. Since APOE4 is a well recognized risk factor for Alzheimer dementia, cognitive status may represent an important confounder between APOE4 and depression. In this investigation, we examined the relationship between the ApolipoproteinE-ε4 allele and depression among elders accounting for cognitive status.

  9. Gold, platinum, and aluminum nanodisk plasmons: material independence, subradiance, and damping mechanisms.

    Science.gov (United States)

    Zorić, Igor; Zäch, Michael; Kasemo, Bengt; Langhammer, Christoph

    2011-04-26

    Localized surface plasmon resonances (LSPR) are collective electronic excitations in metallic nanoparticles. The LSPR spectral peak position, as a function of nanoparticle size and material, is known to depend primarily on dynamic depolarization and electron structure related effects. The former gives rise to the well-known spectral red shift with increasing nanoparticle size. A corresponding understanding of the LSPR spectral line width for a wide range of nanoparticle sizes and different metals does, however, not exist. In this work, the radiative and nonradiative damping contributions to the LSPR line width over a broad nanoparticle size range (40-500 nm) for a selection of three metals with fundamentally different bulk dielectric properties (Au, Pt, and Al) are explored experimentally and theoretically. Excellent agreement was obtained between the observed experimental trends and the predictions based on electrostatic spheroid theory (MLWA), and the obtained results were successfully related to the specific band structure of the respective metal. Moreover, for the first time, a clear transition from a radiation damping dominated to a quenched radiation damping regime (subradiance) in large nanoparticles was observed and probed by varying the electron density through appropriate material choice. To minimize inhomogeneous broadening (commonly present in ensemble-based spectroscopic measurements), a novel, electron-beam lithography (EBL)-based nanofabrication method was developed. The method generates large-area 2D patterns of randomly distributed nanodisks with well-defined size and shape, narrow size distribution, and tunable (minimum) interparticle distance. In order to minimize particle-particle coupling effects, sparse patterns with a large interparticle distance (center-to-center ≥6 particle diameters) were considered. PMID:21438568

  10. CeO2-ZnO hexagonal nanodisks: Efficient material for the degradation of direct blue 15 dye and its simulated dye bath effluent under solar light

    International Nuclear Information System (INIS)

    Highlights: • Synthesis of CeO2-ZnO hexagonal nanodisks. • Excellent morphological, crystalline and photoluminescent properties. • Solar light responsive photocatalyst for degradation of direct blue 15 dye and its simulated dye bath effluent. - Abstract: Well-crystalline CeO2-ZnO hexagonal nanodisks were synthesized by simple and facile chemical reaction process at low-temperature and characterized in detail by using several techniques such as powder X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, thermal gravimetric analysis (TGA), UV–vis diffuse reflectance spectroscopy (DRS), photoluminescence (PL) emission spectroscopy and X-ray photoelectron spectroscopy (XPS). The detailed characterizations results revealed that the prepared samples are well-crystalline with good optical and structural properties and possessing hexagonal morphologies. Further, the prepared material was used as efficient photocatalyst for the photocatalytic degradation of highly hazardous direct blue (DB)-15 dye under solar light irradiation. The CeO2-ZnO hexagonal nanodisks exhibited superior photocatalytic performance towards the degradation of DB 15 dye and its simulated dye bath effluent under solar light. The enhanced photocatalytic activity of CeO2-ZnO hexagonal nanodisks could be attributed to the suppression of photo-induced e−/h+ pair recombination. Moreover, various scavengers have been used to study the role of reactive species in the photo-degradation process

  11. Role of Apolipoprotein E in Anxiety

    Directory of Open Access Journals (Sweden)

    Jacob Raber

    2007-07-01

    Full Text Available Anxiety is most common among Alzheimer's disease (AD patients with an age at onset under age 65. Apolipoprotein E4 (apoE4 is a risk factor for developing AD at an earlier age and might contribute to this effect. In mice, apoE plays a role in the regulation of anxiety, which might involve histamine receptor-mediated signaling and steroidogenesis in the adrenal gland. In addition, human apoE isoforms have differential effects on anxiety in adult mice lacking apoE and probable AD patients. Compared to wild-type mice, mice lacking apoE and apoE4 mice showed pathological alterations in the central nucleus of the amygdala, which is involved in regulation of anxiety. ApoE4, but not mice lacking apoE, or apoE3 mice showed impaired dexamethasone suppression of plasma corticosterone. Understanding how apoE modulates measures of anxiety might help the developments of therapeutic targets to reduce or even prevent measures of anxiety in health and in dementing illnesses.

  12. DMPD: Regulation of endogenous apolipoprotein E secretion by macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18388328 Regulation of endogenous apolipoprotein E secretion by macrophages. Kockx ...svg) (.html) (.csml) Show Regulation of endogenous apolipoprotein E secretion by macrophages. PubmedID 18388...328 Title Regulation of endogenous apolipoprotein E secretion by macrophages. Aut

  13. Construction of GPx active centers on natural protein nanodisk/nanotube: a new way to develop artificial nanoenzyme.

    Science.gov (United States)

    Hou, Chunxi; Luo, Quan; Liu, Jinliang; Miao, Lu; Zhang, Chunqiu; Gao, Yuzhou; Zhang, Xiyu; Xu, Jiayun; Dong, Zeyuan; Liu, Junqiu

    2012-10-23

    Construction of catalytic centers on natural protein aggregates is a challenging topic in biomaterial and biomedicine research. Here we report a novel construction of artificial nanoenzyme with glutathione peroxidase (GPx)-like function. By engineering the surface of tobacco mosaic virus (TMV) coat protein, the main catalytic components of GPx were fabricated on TMV protein monomers. Through direct self-assembly of the functionalized viral coat proteins, the multi-GPx centers were installed on these well-defined nanodisks or nanotubes. With the help of muti-selenoenzyme centers, the resulting organized nanoenzyme exhibited remarkable GPx activity, even approaching the level of natural GPx. The antioxidation study on subcell mitochondrial level demonstrated that virus-based nanoenzyme exerted excellent capacity for protecting cell from oxidative damage. This strategy represents a new way to develop artificial nanoenzymes. PMID:22992167

  14. Core-Shell Structured Dielectric-Metal Circular Nanodisk Antenna: Gap Plasmon Assisted Magnetic Toroid-like Cavity Modes

    CERN Document Server

    Zhang, Qiang; Zhang, Xiao Ming; Han, Dezhuan; Gao, Lei

    2014-01-01

    Plasmonic nanoantennas, the properties of which are essentially determined by their resonance modes, are of interest both fundamentally and for various applications. Antennas with various shapes, geometries and compositions have been demonstrated, each possessing unique properties and potential applications. Here, we propose the use of a sidewall coating as an additional degree of freedom to manipulate plasmonic gap cavity modes in strongly coupled metallic nanodisks. It is demonstrated that for a dielectric middle layer with a thickness of a few tens of nanometers and a sidewall plasmonic coating of more than ten nanometers, the usual optical magnetic resonance modes are eliminated, and only magnetic toroid-like modes are sustainable in the infrared and visible regime. All of these deep-subwavelength modes can be interpreted as an interference effect from the gap surface plasmon polaritons. Our results will be useful in nanoantenna design, high-Q cavity sensing, structured light-beam generation, and photon e...

  15. Static property and current-driven precession of 2π-vortex in nano-disk with Dzyaloshinskii-Moriya interaction

    International Nuclear Information System (INIS)

    An interesting type of skyrmion-like spin texture, 2π-vortex, is obtained in a thin nano-disk with Dzyaloshinskii-Moriya interaction. We have simulated the existence of 2π-vortex by micromagnetic method. Furthermore, the spin polarized current is introduced in order to drive the motion of 2π-vortex in a nano-disk with diameter 2 R = 140 nm. When the current density matches with the current injection area, 2π-vortex soon reaches a stable precession (3∼4 ns). The relationship between the precession frequency of 2π-vortex and the current density is almost linear. It may have potential use in spin torque nano-oscillators

  16. Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

    NARCIS (Netherlands)

    Dallinga-Thie, GM; Van Tol, A; Hattori, H; van Vark-van de Zee, LC; Jansen, H; Sijbrands, EJG

    2006-01-01

    Aims/hypothesis: Variation in the human apolipoprotein (APO) A5 gene (APOA5) is associated with elevated plasma triglycerides. However, data on the exact role of plasma concentrations of APOA5 in human triglyceride homeostasis are lacking. In the present study, we estimated plasma APOA5 levels in pa

  17. Apolipoprotein a5 and hypertriglyceridemia in prague hypertriglyceridemic rats

    Czech Academy of Sciences Publication Activity Database

    Kadlecová, Michaela; Hojná, Silvie; Bohuslavová, R.; Hubáček, J. A.; Zicha, Josef; Kuneš, Jaroslav

    2006-01-01

    Roč. 55, č. 4 (2006), s. 373-379. ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/03/0769 Institutional research plan: CEZ:AV0Z50110509 Keywords : metabolic syndrome * apolipoprotein A5 * rat Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  18. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B;

    2004-01-01

    Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... of lipid transfer from the mother to the developing fetus....

  19. Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke

    DEFF Research Database (Denmark)

    Khan, Tauseef A; Shah, Tina; Prieto, David;

    2013-01-01

    At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less c...

  20. Effects of apolipoproteins on the kinetics of cholesterol exchange

    Energy Technology Data Exchange (ETDEWEB)

    Letizia, J.Y.; Phillips, M.C. (Medical College of Pennsylvania, Philadelphia (USA))

    1991-01-22

    The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of ({sup 14}C)cholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid and a trace of ({sup 14}C)cholesterol were incubated with a 10-fold excess of neutral, acceptor, small unilamellar vesicles. The donor and acceptor particles were separated by chromatogrphy of DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. Apolipoproteins A-I, A-II, reduced and carboxymethylated A-11, and B-100 present in SUV at the same lipid/protein (w/w) ratio all enhance the rate of cholesterol exchange to about the same degree. Cholesterol molecules exchange more rapidly from discoidal complexes. Generally, as the diameter of apoprotein/phospholipid/cholesterol discs decreases, t{sub 1/2} for cholesterol exchange decreases. Since small bilayer discs have a relatively high ratio of boundary to face surface area, cholesterol molecules desorb more rapidly than from larger discs. The modulation of lipid packing by the apoprotein molecules present at the surface of lipoprotein particles affects the rate of cholesterol exchange from such particles.

  1. Measurement of the intrinsic damping constant in individual nanodisks of Y3Fe5O12 and Y3Fe5O12|Pt

    International Nuclear Information System (INIS)

    We report on an experimental study on the spin-waves relaxation rate in two series of nanodisks of diameter ϕ=300, 500, and 700 nm, patterned out of two systems: a 20 nm thick yttrium iron garnet (YIG) film grown by pulsed laser deposition either bare or covered by 13 nm of Pt. Using a magnetic resonance force microscope, we measure precisely the ferromagnetic resonance linewidth of each individual YIG and YIG|Pt nanodisks. We find that the linewidth in the nanostructure is sensibly smaller than the one measured in the extended film. Analysis of the frequency dependence of the spectral linewidth indicates that the improvement is principally due to the suppression of the inhomogeneous part of the broadening due to geometrical confinement, suggesting that only the homogeneous broadening contributes to the linewidth of the nanostructure. For the bare YIG nano-disks, the broadening is associated to a damping constant α=4 × 10−4. A threefold increase of the linewidth is observed for the series with Pt cap layer, attributed to the spin pumping effect. The measured enhancement allows to extract the spin mixing conductance found to be G↑↓=1.55 × 1014 Ω−1 m−2 for our YIG(20nm)|Pt interface, thus opening large opportunities for the design of YIG based nanostructures with optimized magnetic losses

  2. Apolipoprotein B is conformationally flexible but anchored at a triolein/water interface: A possible model for lipoprotein surfaces

    OpenAIRE

    Wang, Libo; Walsh, Mary T.; Small, Donald M.

    2006-01-01

    Apolipoprotein B (apoB) is one of a unique group of proteins that form and bind to fat droplets, stabilize the emulsified fat, and direct their metabolism. ApoB, secreted on lipoproteins (emulsions), remains bound during lipid metabolism yet exhibits conformational flexibility. It has amphipathic β-strand (AβS)-rich domains and amphipathic α-helix (AαH)-rich domains. We showed that two consensus AβS peptides of apoB bound strongly to hydrophobic interfaces [triolein/water (TO/W) and dodecane/...

  3. The gender-specific apolipoprotein E genotype influence on the distribution of plasma lipids and apolipoproteins in the population of Rochester, Minnesota. II. Regression relationships with concomitants

    Energy Technology Data Exchange (ETDEWEB)

    Reilly, S.L.; Sing, C.F. (Univ. of Michigan, Ann Arbor (United States)); Ferrell, R.E. (Univ. of Pittsburgh, PA (United States)); Kottke, B.A. (Mayo Clinic, Rochester, MN (United States))

    1992-12-01

    The influence of the apolipoprotein E (Apo E) polymorphism and gender on the regression relationships between each of nine plasma lipid and apolipoprotein traits (total cholesterol; ln triglycerides; high-density-lipoprotein chloesterol; apolipoproteins AI, AII, B, and CII; ln CIII; and ln E) and four concomitants (age, weight, waist-to-hip ratio, and smoking) was studied in 507 unrelated individuals representative of the adult population of Rochester, MN. Analyses are presented separately for females and males. Each lipid and apolipoprotein trait exhibited at least one Apo E genotype-specific regression relationship with the concomitants investigated in this study. In most cases the heterogeneity of regression was associated with differences between the [var epsilon]32 and [var epsilon]33 genotype. This study documents that the influence of Apo E genotype on average levels of plasma lipids and apolipoproteins varies among subdivisions of the population defined by age, body size, and smoking status. 61 refs., 1 fig., 5 tabs.

  4. Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100

    International Nuclear Information System (INIS)

    Familial defective apolipoprotein (apo) B-100 is a genetic disease that leads to hypercholesterolemia and to an increased serum concentration of low density lipoproteins that bind defectively to the apoB,E(LDL) receptor. The disorder appears to result from a mutation in the gene for apoB-100. Extensive sequence analysis of the two alleles of one subject heterozygous for the disorder has revealed a previously unreported mutation in the codon for amino acid 3500 that results in the substitution of glutamine for arginine. This same mutant allele occurs in six other, unrelated subjects and in eight affected relatives in two of these families. A partial haplotype of this mutant apoB-100 allele was constructed by sequence analysis and restriction enzyme digestion at positions where variations in the apoB-100 are known to occur. This haplotype is the same in three probands and four affected members of one family and lacks a polymorphic Xba I site whose presence has been correlated with high cholesterol levels. Thus, it appears that the mutation in the codon for amino acid 3500 (CGG → CAG), a CG mutational hot spot, defines a minor apoB-100 allele associated with defective low density lipoproteins and hypercholesterolemia

  5. Apolipoprotein L-I Promotes Trypanosome Lysis by Forming Pores in Lysosomal Membranes

    Science.gov (United States)

    Pérez-Morga, David; Vanhollebeke, Benoit; Paturiaux-Hanocq, Françoise; Nolan, Derek P.; Lins, Laurence; Homblé, Fabrice; Vanhamme, Luc; Tebabi, Patricia; Pays, Annette; Poelvoorde, Philippe; Jacquet, Alain; Brasseur, Robert; Pays, Etienne

    2005-07-01

    Apolipoprotein L-I is the trypanolytic factor of human serum. Here we show that this protein contains a membrane pore-forming domain functionally similar to that of bacterial colicins, flanked by a membrane-addressing domain. In lipid bilayer membranes, apolipoprotein L-I formed anion channels. In Trypanosoma brucei, apolipoprotein L-I was targeted to the lysosomal membrane and triggered depolarization of this membrane, continuous influx of chloride, and subsequent osmotic swelling of the lysosome until the trypanosome lysed.

  6. Major lipids, apolipoproteins, and risk of vascular disease

    DEFF Research Database (Denmark)

    Collaboration, Emerging Risk Factors; Di Angelantonio, Emanuele; Sarwar, Nadeem;

    2009-01-01

    initial vascular disease from 68 long-term prospective studies, mostly in Europe and North America. During 2.79 million person-years of follow-up, there were 8857 nonfatal myocardial infarctions, 3928 coronary heart disease [CHD] deaths, 2534 ischemic strokes, 513 hemorrhagic strokes, and 2536......CONTEXT: Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified. OBJECTIVE: To assess major lipids and apolipoproteins in vascular risk. DESIGN, SETTING, AND PARTICIPANTS: Individual records were supplied on 302,430 people without...... mg/dL directly measured low-density lipoprotein cholesterol (LDL-C). Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. RESULTS: The rates of CHD per 1000 person-years in the bottom and top thirds of baseline lipid distributions, respectively...

  7. Solubility engineering and crystallization of human apolipoprotein D

    OpenAIRE

    Nasreen, Amber; Vogt, Martin; Kim, Hyun Jin; Eichinger, Andreas; Skerra, Arne

    2006-01-01

    Human apolipoprotein D (ApoD) is a physiologically important member of the lipocalin protein family that was discovered as a peripheral subunit of the high-density lipoprotein (HDL) but is also abundant in other body fluids and organs, including neuronal tissue. Although it has been possible to produce functional ApoD in the periplasm of Escherichia coli and to demonstrate its ligand-binding activity for progesterone and arachidonic acid, the recombinant protein suffers from a pronounced tend...

  8. The Apolipoprotein E Antagonistic Pleiotropy Hypothesis: Review and Recommendations

    OpenAIRE

    Tuminello, Elizabeth R.; S Duke Han

    2011-01-01

    Research on apolipoprotein E (APOE) has consistently revealed a relationship between the gene's ε 4 allele and risk for development of Alzheimer's disease (AD). However, research with younger populations of ε 4 carriers has suggested that the APOE ε 4 allele may in fact be beneficial in earlier ages and may only confer risk of cognitive decline later in life. Accordingly, we and others have proposed that APOE may represent an example of antagonistic pleiotropy. Antagonistic pleiotropy is an e...

  9. The role of apolipoprotein AI domains in lipid binding

    OpenAIRE

    Davidson, W. Sean; Hazlett, Theodore; Mantulin, William W.; Jonas, Ana

    1996-01-01

    Apolipoprotein AI (apoAI) is the principal protein constituent of high density lipoproteins and it plays a key role in human cholesterol homeostasis; however, the structure of apoAI is not clearly understood. To test the hypothesis that apoAI is organized into domains, three deletion mutants of human apoAI expressed in Escherichia coli were studied in solution and in reconstituted high density lipoprotein particles. Each mutant lacked one of three specific regions ...

  10. Serum lipid and apolipoprotein distributions in Hong Kong Chinese.

    OpenAIRE

    Fong, P C; Tam, S C; Tai, Y. T.; Lau, C P; Lee, J.; Sha, Y Y

    1994-01-01

    STUDY OBJECTIVE--The aim was to describe the distribution of lipids and apolipoproteins in the Chinese population in Hong Kong. DESIGN--This was a prospective, cross sectional, population based survey. SETTINGS--The study was conducted in a single, self referred, out patient screening centre. PARTICIPANTS--Altogether 825 Chinese adults aged > or = 20 years were screened. One hundred subjects who had previously had lipid measurement and 29 who were taking lipid modifying drugs were excluded bu...

  11. Oligonucleotide-mediated gene editing of Apolipoprotein A-I.

    OpenAIRE

    Disterer, P

    2008-01-01

    Apolipoprotein A-I (ApoA-I) is the major protein constituent of high density lipoprotein (HDL) and controls reverse cholesterol transport, an important process in preventing atherosclerosis. A natural point mutation, ApoA-lMiiano (ApoA-Im) enhances the atheroprotective potential of HDL. Here, I attempt to introduce this specific modification into the genome of mammalian cells using the gene therapy strategy of oligonucleotide-mediated gene editing. I showed successful APOA-I gene editing in r...

  12. Hereditary Amyloid Cardiomyopathy Caused by a Variant Apolipoprotein A1

    OpenAIRE

    Hamidi Asl, Ladan; Liepnieks, Juris J.; Hamidi Asl, Kamran; Uemichi, Tomoyuki; Moulin, Georges; Desjoyaux, Emmanuel; Loire, Robert; Delpech, Marc; Grateau, Gilles; Benson, Merrill D.

    1999-01-01

    Autosomal dominant hereditary amyloidosis with a unique cutaneous and cardiac presentation and death from heart failure by the sixth or seventh decade was found to be associated with a previously unreported point mutation (thymine to cytosine, nt 1389) in exon 4 of the apolipoprotein A1 (apoA1) gene. The predicted substitution of proline for leucine at amino acid position 90 was confirmed by structural analysis of amyloid protein isolated from cardiac deposits of amyloid. The subunit protein ...

  13. Effect of fatty acids on the synthesis and secretion of apolipoprotein B by rat hepatocytes

    International Nuclear Information System (INIS)

    The modulation of apolipoprotein B synthesis and secretion by fatty acids in rat hepatocytes was studied. Maximum apolipoprotein B production was obtained in the case of oleic acid followed by linoleic, stearic and palmitic/linolenic acid when compared to control which was not supplemented with any fatty acids. Oleic acid was found to exert a concentration dependent increase in the secretion of [3H] apolipoprotein B into the medium while that associated with the cell layer was not affected. Pulse chase experiments in the presence of oleic acid showed that it caused an increase in the secretion of apolipoprotein B into the medium. 14C-acetate incorporation into cholesterol and cholesteryl ester associated with the cell layer and secreted very low density lipoproteins also showed an increase in the presence of oleic acid indicating an increase in cholesterogenesis. The effect of oleic acid on [3H] apolipoprotein B and very low density lipoprotein secretion appeared to be mediated through cholesterol as (i)ketoconazole, an inhibitor of cholesterol synthesis caused significant reduction in the stimulatory effect of oleic acid on apolipoprotein secretion and (ii) mevinolin, another inhibitor of cholesterol synthesis also reversed the stimulatory effect of oleic acid on apolipoprotein B secretion. These results indicated that oleic acid may influence apolipoprotein B synthesis and secretion in hepatocytes probably by affecting cholesterol/cholesteryl ester formation which may be a critical component in the secretion of apolipoprotein B as lipoproteins. (author). 21 refs., 4 figs., 2 tabs

  14. Influences of apolipoprotein E on soluble and heparin-immobilized hepatic lipase

    Energy Technology Data Exchange (ETDEWEB)

    Landis, B.A.; Rotolo, F.S.; Meyers, W.C.; Clark, A.B.; Quarfordt, S.H.

    1987-06-01

    The effect of human apolipoprotein E (apoE), either alone or in combination with apoC, on the lipolysis of a radiolabeled triglyceride emulsion was studied with hepatic lipase in solution and immobilized on heparin-Sepharose. The soluble hepatic lipase was inhibited, whereas the heparin-immobilized lipase was stimulated by apoE. This stimulation was attenuated by combining apoE with either apoC-II or C-III. The heparin-immobilized lipase demonstrated much less lipolysis of the zwitterionic phosphatidylcholine-stabilized triglyceride emulsion than did the soluble enzyme. This difference was less when the emulsion was stabilized by a nonionic detergent. apoE inhibited lipase activity when assayed under conditions (0.4 M NaCl) of bound enzyme and unbound substrate. Increasing the emulsion apoE content beyond optimum inhibited lipolysis by the immobilized enzyme. Kinetic analysis of phosphatidylcholine-stabilized triglyceride emulsions revealed a significant decrease in immobilized enzyme K/sub m/ and an increase in V/sub max/ when the emulsion was supplemented with apoE. Distributing the immobilized lipase in clustered aggregates produced more lipolysis than when the same enzyme content was uniformly bound.

  15. Influences of apolipoprotein E on soluble and heparin-immobilized hepatic lipase

    International Nuclear Information System (INIS)

    The effect of human apolipoprotein E (apoE), either alone or in combination with apoC, on the lipolysis of a radiolabeled triglyceride emulsion was studied with hepatic lipase in solution and immobilized on heparin-Sepharose. The soluble hepatic lipase was inhibited, whereas the heparin-immobilized lipase was stimulated by apoE. This stimulation was attenuated by combining apoE with either apoC-II or C-III. The heparin-immobilized lipase demonstrated much less lipolysis of the zwitterionic phosphatidylcholine-stabilized triglyceride emulsion than did the soluble enzyme. This difference was less when the emulsion was stabilized by a nonionic detergent. apoE inhibited lipase activity when assayed under conditions (0.4 M NaCl) of bound enzyme and unbound substrate. Increasing the emulsion apoE content beyond optimum inhibited lipolysis by the immobilized enzyme. Kinetic analysis of phosphatidylcholine-stabilized triglyceride emulsions revealed a significant decrease in immobilized enzyme K/sub m/ and an increase in V/sub max/ when the emulsion was supplemented with apoE. Distributing the immobilized lipase in clustered aggregates produced more lipolysis than when the same enzyme content was uniformly bound

  16. Subtractive Color Filters Based on a Silicon-Aluminum Hybrid-Nanodisk Metasurface Enabling Enhanced Color Purity.

    Science.gov (United States)

    Yue, Wenjing; Gao, Song; Lee, Sang-Shin; Kim, Eun-Soo; Choi, Duk-Yong

    2016-01-01

    Highly efficient subtractive tri-color filters of cyan, magenta, and yellow with enhanced color purity and robustness have been proposed and realized, by exploiting a silicon-aluminum (Si-Al) hybrid-nanodisk (ND) metasurface atop a Si substrate. The aspect ratio of the Si-Al hybrid ND is much lower than that of the conventional Si nanowire, which is disadvantageous due to its fragility and low color purity. In response to incident light impinging upon the metasurface, the hybrid-NDs individually play the role in exciting a magnetic dipole (MD) resonance through the mediation of Mie-scattering between the hybrid ND and air. The light stored in the resonance is coupled to the substrate, giving rise to a suppressed reflection. By virtue of the top Al ND, the excited MD resonance is strongly confined by the Si ND. As a consequence, a near-zero resonant dip that exhibits high off-resonance reflection and narrow bandwidth is produced for embodying highly efficient tri-color filters with enhanced color purity. The spectral position can be tuned by a simple adjustment of the hybrid-ND diameter. A full-color palette was successfully created with a high color purity and large color gamut. The proposed devices may be applied for photorealistic high-resolution color printing and holographic displays. PMID:27407024

  17. Specificity determinants in the interaction of apolipoprotein(a) kringles with tetranectin and LDL

    DEFF Research Database (Denmark)

    Caterer, Nigel R; Graversen, Jonas Heilskov; Jacobsen, Christian;

    2002-01-01

    Lipoprotein(a) is composed of low density lipoprotein and apolipoprotein(a). Apolipoprotein(a) has evolved from plasminogen and contains 10 different plasminogen kringle 4 homologous domains [KIV(1-110)]. Previous studies indicated that lipoprotein(a) non-covalently binds the N-terminal region of...

  18. Truncated variants of apolipoprotein B cause hypobetalipoproteinaemia

    Energy Technology Data Exchange (ETDEWEB)

    Collins, D.R.; Knott, T.J.; Pease, R.J.; Powell, L.M.; Wallis, S.C.; Robertson, S.; Pullinger, C.R.; Lloyd, K.; Miller, N.E.; Muller, D.; Scott, J. (MRC Clinical Research Centre, Harrow (England)); Humphries, S.E.; Talmud, P.J. (Charing Cross Sunley Research Centre, London (England)); Milne, R.W.; Marcel, Y.L. (Clinical Research Institute of Montreal, Quebec (Canada))

    1988-09-12

    Familial hypobetalipoproteinaemia is a rare autosomal dominant disorder in which levels of apo-B-containing plasma lipoproteins are approximately half-normal in heterozygotes and virtually absent in homozygotes. Here the authors describe mutations of the apo-B gene that cause two different truncated variants of apo-B in unrelated individuals with hypobetalipoproteinaemia. One variant is predicted to be 1,799 amino acids long and arises from deletion of a single nucleotide (G) from leucine codon 1,794. This protein was found at low levels in very low density and low density lipoprotein fractions in the blood. The second, shorter variant is caused by mutation of a CpG dinucleotide in arginine codon 1,306 converting it to a stop codon and predicting a protein of 1,305 residues. The differences in size and behavior of these two variants compared to apo-B100 or apo-B48 point to domains that may be important for the assembly, secretion or stability of apo-B-containing lipoproteins.

  19. The Effects of Ginger on Fasting Blood Sugar, Hemoglobin A1c, Apolipoprotein B, Apolipoprotein A-I and Malondialdehyde in Type 2 Diabetic Patients

    OpenAIRE

    Khandouzi, Nafiseh; Shidfar, Farzad; Rajab, Asadollah; Rahideh, Tayebeh; Hosseini, Payam; Mir Taheri, Mohsen

    2015-01-01

    Diabetes mellitus is the most common endocrine disorder, causes many complications such as micro- and macro-vascular diseases. Anti-diabetic, hypolipidemic and anti-oxidative properties of ginger have been noticed in several researches. The present study was conducted to investigate the effects of ginger on fasting blood sugar, Hemoglobin A1c, apolipoprotein B, apolipoprotein A-I, and malondialdehyde in type 2 diabetic patients. In a randomized, double-blind, placebo-controlled, clinical tria...

  20. Reduced apolipoprotein glycosylation in patients with the metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Olga V Savinova

    Full Text Available The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls.Very low density (VLDL, intermediate/low density (IDL/LDL, hereafter LDL, and high density lipoproteins (HDL fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays.Metabolic syndrome patients differed from healthy controls in the following ways: (1 total plasma--apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2 VLDL--apoB, apoC3, and apoE were increased; (3 LDL--apoC3 was increased, (4 HDL--associated constitutive serum amyloid A protein (SAA4 was reduced (p<0.05 vs. controls for all. In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all. Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all. Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001.Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.

  1. Synthesis of antibacterial silver-based nanodisks and dendritic structures mediated by royal jelly

    OpenAIRE

    Mendoza-Reséndez, R.; Gómez-Treviño, A.; Barriga-Castro, E.D.; Núñez, Nuria O.; Luna, C.

    2014-01-01

    The one-step preparation of silver nanoparticles and dendritic structures mediated by aqueous royal jelly solutions has been investigated for the first time. It has been found that royal jelly (RJ) is a complex organic matrix that can be simultaneously used as a reducing and stabilizing agent in the chemical synthesis of colloidal silver-based nanostructures from aqueous AgNO3 solutions, without the requirement of additional reagents or heating sources to initiate the oxidation-reduction reac...

  2. Apolipoproteins C-I and C-III Inhibit Lipoprotein Lipase Activity by Displacement of the Enzyme from Lipid Droplets*

    Science.gov (United States)

    Larsson, Mikael; Vorrsjö, Evelina; Talmud, Philippa; Lookene, Aivar; Olivecrona, Gunilla

    2013-01-01

    Apolipoproteins (apo) C-I and C-III are known to inhibit lipoprotein lipase (LPL) activity, but the molecular mechanisms for this remain obscure. We present evidence that either apoC-I or apoC-III, when bound to triglyceride-rich lipoproteins, prevent binding of LPL to the lipid/water interface. This results in decreased lipolytic activity of the enzyme. Site-directed mutagenesis revealed that hydrophobic amino acid residues centrally located in the apoC-III molecule are critical for attachment to lipid emulsion particles and consequently inhibition of LPL activity. Triglyceride-rich lipoproteins stabilize LPL and protect the enzyme from inactivating factors such as angiopoietin-like protein 4 (angptl4). The addition of either apoC-I or apoC-III to triglyceride-rich particles severely diminished their protective effect on LPL and rendered the enzyme more susceptible to inactivation by angptl4. These observations were seen using chylomicrons as well as the synthetic lipid emulsion Intralipid. In the presence of the LPL activator protein apoC-II, more of apoC-I or apoC-III was needed for displacement of LPL from the lipid/water interface. In conclusion, we show that apoC-I and apoC-III inhibit lipolysis by displacing LPL from lipid emulsion particles. We also propose a role for these apolipoproteins in the irreversible inactivation of LPL by factors such as angptl4. PMID:24121499

  3. Apolipoproteins C-I and C-III inhibit lipoprotein lipase activity by displacement of the enzyme from lipid droplets.

    Science.gov (United States)

    Larsson, Mikael; Vorrsjö, Evelina; Talmud, Philippa; Lookene, Aivar; Olivecrona, Gunilla

    2013-11-22

    Apolipoproteins (apo) C-I and C-III are known to inhibit lipoprotein lipase (LPL) activity, but the molecular mechanisms for this remain obscure. We present evidence that either apoC-I or apoC-III, when bound to triglyceride-rich lipoproteins, prevent binding of LPL to the lipid/water interface. This results in decreased lipolytic activity of the enzyme. Site-directed mutagenesis revealed that hydrophobic amino acid residues centrally located in the apoC-III molecule are critical for attachment to lipid emulsion particles and consequently inhibition of LPL activity. Triglyceride-rich lipoproteins stabilize LPL and protect the enzyme from inactivating factors such as angiopoietin-like protein 4 (angptl4). The addition of either apoC-I or apoC-III to triglyceride-rich particles severely diminished their protective effect on LPL and rendered the enzyme more susceptible to inactivation by angptl4. These observations were seen using chylomicrons as well as the synthetic lipid emulsion Intralipid. In the presence of the LPL activator protein apoC-II, more of apoC-I or apoC-III was needed for displacement of LPL from the lipid/water interface. In conclusion, we show that apoC-I and apoC-III inhibit lipolysis by displacing LPL from lipid emulsion particles. We also propose a role for these apolipoproteins in the irreversible inactivation of LPL by factors such as angptl4. PMID:24121499

  4. Apolipoprotein E*3-Leiden transgenic mice mode for hypolipidaemic drugs

    OpenAIRE

    Vlijmen, B.J.M. van; Pearce, N.J.; Bergö, M.; Staels, B.; Yates, J.W.; Gribble, A.D.; Bond, B.C.; Hofker, M H; Havekes, L. M.; Groot, P H E

    1998-01-01

    Apolipoprotein (APO) E*3-Leiden mice with impaired chylomicron and VLDL (very low density lipoprotein) remnant metabolism display hyperlipidaemia and atherosclerosis. In the present study, these mice were used for testing the hypolipidaemic effect of two marketed agents, lovastatin (CAS 75330-75-5) and gemfibrozil (CAS 25812-30-0) as well as a novel compound, SB 204990 (the 5- ring lactone of ±(3R*,5S*) 3-carboxy-11-(2,4-dichlorophenyl)-3,5- dihydroxyundecanoic acid, CAS 154566-12-8), a poten...

  5. An abundant dysfunctional apolipoprotein A1 in human atheroma

    OpenAIRE

    Huang, Ying; DiDonato, Joseph A.; Levison, Bruce S.; Schmitt, Dave; Li, Lin; Wu, Yuping; Buffa, Jennifer; Kim, Timothy; Gerstenecker, Gary; Gu, Xiaodong; Kadiyala, Chandra; Wang, Zeneng; Culley, Miranda K.; Hazen, Jennie E.; DiDonato, Anthony J.

    2014-01-01

    Recent studies indicate high density lipoproteins (HDL) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma, are dysfunctional and extensively oxidized by myeloperoxidase (MPO), while in vitro oxidation of apoA1/HDL by MPO impairs its cholesterol acceptor function. We developed a high affinity monoclonal antibody (mAb) that specifically recognizes apoA1/HDL modified by the MPO/H2O2/Cl-system using phage display affinity maturation. An oxindolyl alanine...

  6. Both serum apolipoprotein B and the apolipoprotein B/apolipoprotein A-I ratio are associated with carotid intima-media thickness.

    Directory of Open Access Journals (Sweden)

    Fei Huang

    Full Text Available BACKGROUND: Previous studies indicated that apolipoprotein measurements predicted cardiovascular disease (CVD risk; however, associations between apolipoproteins and carotid intima-media thickness (CIMT were less explored. METHODOLOGY AND PRINCIPAL FINDINGS: The cross-sectional study included 6069 participants aged 40 years or older with NGT from Shanghai, China. Serum fasting traditional lipids (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG], apoA-I and apoB were assessed. A high-resolution B-mode ultrasonography was performed to measure CIMT. We found CIMT increased progressively across the quartiles of serum apoB (p for trend <0.0001. In logistic regression, concentrations of apoB (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.18-1.36, TC (OR 1.23, 95% CI 1.14-1.32, LDL-C (OR 1.25, 95% CI 1.16-1.34 and TG (OR 1.11, 95% CI 1.04-1.20 were significantly related to elevated CIMT after adjusted for age and sex. Meanwhile, the apoB/apoA-I ratio (OR 1.25, 95% CI 1.17-1.34 related to elevated CIMT. ApoB (OR 1.23, 95% CI 1.00-1.51 and the apoB/apoA-I ratio (OR 1.19, 95% CI 1.04-1.36 remained significantly associated with elevated CIMT, after adjusted for the traditional CVD risk factors including traditional lipids. CONCLUSIONS AND SIGNIFICANCE: There were significant associations between serum apoB, the apoB/apoA-I ratio and elevated CIMT. Serum apoB and the apoB/apoA-I ratio might be independent predictors of early atherosclerosis in NGT.

  7. CeO{sub 2}-ZnO hexagonal nanodisks: Efficient material for the degradation of direct blue 15 dye and its simulated dye bath effluent under solar light

    Energy Technology Data Exchange (ETDEWEB)

    Lamba, Randeep [Department of Chemistry, Panjab University, Chandigarh 160014 (India); Umar, Ahmad, E-mail: ahmadumar786@gmail.com [Department of Chemistry, College of Science and Arts, Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia); Promising Centre for Sensors and Electronic Devices (PCSED), Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia); Mehta, Surinder Kumar [Department of Chemistry, Panjab University, Chandigarh 160014 (India); Kansal, Sushil Kumar, E-mail: sushilkk1@yahoo.co.in [Dr. S.S. Bhatnagar University Institute of Chemical Engineering and Technology, Panjab University, Chandigarh 160014 (India)

    2015-01-25

    Highlights: • Synthesis of CeO{sub 2}-ZnO hexagonal nanodisks. • Excellent morphological, crystalline and photoluminescent properties. • Solar light responsive photocatalyst for degradation of direct blue 15 dye and its simulated dye bath effluent. - Abstract: Well-crystalline CeO{sub 2}-ZnO hexagonal nanodisks were synthesized by simple and facile chemical reaction process at low-temperature and characterized in detail by using several techniques such as powder X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, thermal gravimetric analysis (TGA), UV–vis diffuse reflectance spectroscopy (DRS), photoluminescence (PL) emission spectroscopy and X-ray photoelectron spectroscopy (XPS). The detailed characterizations results revealed that the prepared samples are well-crystalline with good optical and structural properties and possessing hexagonal morphologies. Further, the prepared material was used as efficient photocatalyst for the photocatalytic degradation of highly hazardous direct blue (DB)-15 dye under solar light irradiation. The CeO{sub 2}-ZnO hexagonal nanodisks exhibited superior photocatalytic performance towards the degradation of DB 15 dye and its simulated dye bath effluent under solar light. The enhanced photocatalytic activity of CeO{sub 2}-ZnO hexagonal nanodisks could be attributed to the suppression of photo-induced e{sup −}/h{sup +} pair recombination. Moreover, various scavengers have been used to study the role of reactive species in the photo-degradation process.

  8. Multi-resonant silver nano-disk patterned thin film hydrogenated amorphous silicon solar cells for Staebler-Wronski effect compensation

    CERN Document Server

    Vora, Ankit; Pearce, Joshua M; Bergstrom, Paul L; Güney, Durdu Ö

    2014-01-01

    We study polarization independent improved light trapping in commercial thin film hydrogenated amorphous silicon (a-Si:H) solar photovoltaic cells using a three-dimensional silver array of multi-resonant nano-disk structures embedded in a silicon nitride anti-reflection coating (ARC) to enhance optical absorption in the intrinsic layer (i-a-Si:H) for the visible spectrum for any polarization angle. Predicted total optical enhancement (OE) in absorption in the i-a-Si:H for AM-1.5 solar spectrum is 18.51% as compared to the reference, and producing a 19.65% improvement in short-circuit current density (JSC) over 11.7 mA/cm2 for a reference cell. The JSC in the nano-disk patterned solar cell (NDPSC) was found to be higher than the commercial reference structure for any incident angle. The NDPSC has a multi-resonant optical response for the visible spectrum and the associated mechanism for OE in i-a-Si:H layer is excitation of Fabry-Perot resonance facilitated by surface plasmon resonances. The detrimental Staebl...

  9. Intracellular and extracellular processing of human apolipoprotein A-I: secreted apolipoprotein A-I isoprotein 2 is a propeptide.

    OpenAIRE

    Zannis, V I; Karathanasis, S K; Keutmann, H. T.; Goldberger, G; Breslow, J L

    1983-01-01

    We have recently proposed that the major secreted isoprotein form of human apolipoprotein A-I (designated apo A-I2) is modified extracellularly to become the predominant apo A-I form seen in plasma (designated apo A-I4). In the current report we demonstrate that the primary translation product of human apo A-I (designated apo A-I2p) has a 24-amino-acid NH2-terminal extension with a sequence of Met-Lys-Ala-Ala-Val-Leu-Thr-Leu-Ala-Val-Leu-Phe- Leu-Thr-Gly-Ser-Gln-Ala-Arg-His-Phe-Trp-Gln-Gln. Th...

  10. Apolipoprotein E Related Co-Morbidities and Alzheimer's Disease.

    Science.gov (United States)

    Singhrao, Sim K; Harding, Alice; Chukkapalli, Sasanka; Olsen, Ingar; Kesavalu, Lakshmyya; Crean, StJohn

    2016-01-01

    The primary goal of advancement in clinical services is to provide a health care system that enhances an individual's quality of life. Incidence of diabetes mellitus, cardiovascular disease, and associated dementia coupled with the advancing age of the population, have led to an increase in the worldwide challenge to the healthcare system. In order to overcome these challenges, prior knowledge of common, reliable risk factors and their effectors is essential. Oral health constitutes one such relatively unexplored but indispensable risk factor for aforementioned co-morbidities, in the form of poor oral hygiene and tooth loss during aging. Behavioral traits such as low education, smoking, poor diet, neglect of oral health, lack of exercise, and hypertension are few of the risk factors that are shared commonly among these conditions. In addition, common genetic susceptibility traits such as the apolipoprotein E gene, together with an individual's lifestyle can also influence the development of co-morbidities such as periodontitis, atherosclerosis/stroke, diabetes, and Alzheimer's disease. This review specifically addresses the susceptibility of apolipoprotein E gene allele 4 as the plausible commonality for the etiology of co-morbidities that eventually result from periodontal diseases and ultimately progress to dementia. PMID:26923007

  11. Apolipoprotein Mimetic Peptides: A New Approach for the Treatment of Asthma

    Directory of Open Access Journals (Sweden)

    Xianglan eYao

    2012-03-01

    Full Text Available New treatments are needed for severe asthmatics to improve disease control and avoid severe toxicities associated with oral corticosteroids. We have used a murine model of house dust mite (HDM-induced asthma to identify steroid-unresponsive genes that might represent targets for new therapeutic approaches for severe asthma. This strategy identified apolipoprotein E as a steroid-unresponsive gene with increased mRNA expression in the lungs of HDM-challenged mice. Furthermore, apolipoprotein E functioned as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia in experimental HDM-induced asthma. The ability of apolipoprotein E, which is expressed by lung macrophages, to attenuate AHR and goblet cell hyperplasia is mediated by low density lipoprotein (LDL receptors expressed by airway epithelial cells. Consistent with this, administration of an apolipoprotein E mimetic peptide, corresponding to amino acids 130 to 149 of the LDL receptor-binding domain of the holo-apoE protein, significantly reduced AHR and goblet cell hyperplasia in HDM-challenged apoE-/- mice. These findings identified the apolipoprotein E - LDL receptor pathway as a new druggable target for asthma that can be activated by administration of apoE mimetic peptides. Similarly, apolipoprotein A-I may have therapeutic potential in asthma based upon its anti-inflammatory, anti-oxidative and anti-fibrotic properties. Furthermore, administration of apolipoprotein A-I mimetic peptides has attenuated airway inflammation, airway remodeling and airway hyperreactivity in murine models of experimental asthma. Thus, site-directed delivery of inhaled apolipoprotein E or apolipoprotein A-I mimetic peptides may represent novel treatment approaches that can be developed for asthma, including severe disease.

  12. Relationship between depression and apolipoproteins A and B: a case-control study

    Directory of Open Access Journals (Sweden)

    Masoumeh Sadeghi

    2011-01-01

    Full Text Available OBJECTIVE: To investigate the relation between major depressive disorder and metabolic risk factors of coronary heart disease. INTRODUCTION: Little evidence is available indicating a relationship between major depressive disorder and metabolic risk factors of coronary heart disease such as lipoprotein and apolipoprotein. METHODS: This case-control study included 153 patients with major depressive disorder who fulfilled the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV, and 147 healthy individuals. All participants completed a demographic questionnaire and Hamilton rating scale for depression. Anthropometric characteristics were recorded. Blood samples were taken and total cholesterol, high-and low-density lipoproteins and apolipoproteins A and B were measured. To analyze the data, t-test, χ2 test, Pearson correlation test and linear regression were applied. RESULTS: Depression was a negative predictor of apolipoprotein A (β = -0.328, p<0.01 and positive predictor of apolipoprotein B (β = 0.290, p<0.05. Apolipoprotein A was inversely predicted by total cholesterol (β = -0.269, p<0.05 and positively predicted by high-density lipoprotein (β = 0.401, p<0.01. Also, low-density lipoprotein was a predictor of apolipoprotein B (β = 0.340, p<0.01. The severity of depression was correlated with the increment in serum apolipoprotein B levels and the decrement in serum apolipoprotein A level. CONCLUSION: In view of the relationship between apolipoproteins A and B and depression, it would seem that screening of these metabolic risk factors besides psychological interventions is necessary in depressed patients

  13. Characterization of the metabolic syndrome by apolipoproteins in the Oklahoma Cherokee.

    Science.gov (United States)

    Alaupovic, Petar; Blackett, Piers; Wang, Wenyu; Lee, Elisa

    2008-01-01

    Native Americans are susceptible to type 2 diabetes and associated cardiovascular risk that precedes the diabetes. Nondiabetic Cherokee adolescents and young adults were studied for association of apolipoproteins A-I, B, and C-III with the metabolic syndrome, homeostasis model assessment-insulin resistance (HOMA-IR), and body mass index. Apolipoproteins, lipids, selected ratios, and HOMA-IR changed adversely according to the number of metabolic syndrome criteria present (PCherokee have a high prevalence of the metabolic syndrome, which is associated with atherosclerotic lipoprotein particles containing apolipoprotein C-III and B. PMID:19040586

  14. A Proteoliposome Containing Apolipoprotein A-I Mutant (V156K) Enhances Rapid Tumor Regression Activity of Human Origin Oncolytic Adenovirus in Tumor-Bearing Zebrafish and Mice

    OpenAIRE

    Seo, Juyi; Yun, Chae-Ok; Kwon, Oh-Joon; Choi, Eun-Jin; Song, Jae-Young; Choi, Inho; Cho, Kyung-Hyun

    2012-01-01

    We recently reported that the efficiency of adenoviral gene delivery and virus stability are significantly enhanced when a proteoliposome (PL) containing apolipoprotein (apo) A-I is used in an animal model. In the current study, we tested tumor removal activity of oncolytic adenovirus (Ad) using PL-containing wildtype (WT) or V156K. Oncolytic Ad with or without PL was injected into tumors of zebrafish and nude mice as a Hep3B tumor xenograft model. The V156K-PL-Ad-injected zebrafish, group sh...

  15. Deletion of sirtuin 6 accelerates endothelial dysfunction and atherosclerosis in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Liu, Zhiping; Wang, Jiaojiao; Huang, Xiaoyang; Li, Zhuoming; Liu, Peiqing

    2016-06-01

    Sirtuin 6 (SIRT6) is a chromatin-associated deacetylase that plays a leading role in genomic stability and aging. However, the precise role of SIRT6 in atherosclerosis, an aging-associated cardiovascular disease, remains elusive. This study aims at defining the role of SIRT6 in atherosclerotic lesion development. SIRT6 messenger RNA and protein expression are markedly decreased in atherosclerotic aortas of apolipoprotein E-deficient (ApoE(-/-)) mice fed a high-cholesterol diet. SIRT6 was knocked down in ApoE(-/-) mice using small hairpin RNAs (shRNAs) lentivirus injection. SIRT6-shRNA-treated ApoE(-/-) mice showed impaired endothelium-dependent vasodilation, increased plaque size (in aortic sinus, aortic root and en face aorta), and augmented plaque vulnerability (evidenced by increased necrotic core areas and macrophage accumulation and reduced collagen content). At the cellular level, SIRT6 depletion by RNA interference in human umbilical vein endothelial cells significantly increased monocyte adhesion to endothelial cells by inducing the expression of intracellular adhesion molecule-1. Consistently, intracellular adhesion molecule-1 expression was significantly upregulated in aortic endothelium of SIRT6-shRNA-treated ApoE(-/-) mice compared with controls. In sum, the aforementioned findings suggest that SIRT6 is a primary negative regulation factor in endothelial dysfunction and atherosclerosis development. As a result, SIRT6 is a promising therapeutic target for treating atherosclerosis and its cardiovascular complications. PMID:26924042

  16. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B;

    2004-01-01

    Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... early during pregnancy in the placenta. To examine whether the human placenta produces lipoproteins, we examined apoB and microsomal triglyceride transfer protein (MTP) mRNA expression in placental biopsies. ApoB and MTP are mandatory for assembly and secretion of apoB-containing lipoproteins. Both...... lipoproteins secreted from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm. These results demonstrate that human placenta expresses both apoB and MTP and consequently synthesize and secrete apoB-100-containing lipoproteins. Placental lipoprotein formation constitutes a novel pathway...

  17. Antiatherogenic effects of oleanolic acid in apolipoprotein E knockout mice

    DEFF Research Database (Denmark)

    Buus, Niels Henrik; Hansson, Nicolaj Christopher; Rodriguez-Rodriguez, Rosalia;

    2011-01-01

    Oleanolic acid (OA) is a plant triterpenoid steroid with potentially antiatherogenic properties. We investigated whether OA affected atherosclerosis development and vascular function in apolipoprotein E knockout (ApoE(-/-)) mice. ApoE(-/-) mice were fed a high cholesterol Western-type diet in...... combination with OA (100 mg/kg/day), fluvastatin (5 mg/kg/day) or vehicle, with wild type (WT) mice serving as controls. After 8 weeks of treatment atherosclerotic plaque areas in the aortic arch and plasma lipid concentrations were determined. Vasoconstriction and relaxation of the proximal part of aorta...... were investigated in vitro. Inducible nitric oxide synthase (iNOS) was visualized using immunoblotting. As opposed to WT and fluvastatin- and vehicle-treated mice, OA-fed ApoE(-/-) mice gained no weight during the treatment period. Plasma concentrations of total-cholesterol and triglyceride were not...

  18. Cardiovascular effects of uremia in apolipoprotein E-deficient mice

    DEFF Research Database (Denmark)

    Bro, Susanne

    2009-01-01

    of smooth muscle cell assigned genes indicates that besides intimal atherosclerosis, uremic vasculopathy in apoE-/- mice is characterized by a uremia-specific medial smooth muscle cell degeneration. Oxidative stress could also be important for the development of atherosclerotic lesions in uremia. In...... muscle cell degeneration. Furthermore, the studies suggested that vascular inflammation and systemic oxidative stress may explain some of the proatherogenic effects of uremia in mice. Interestingly, the accelerated atherosclerosis could be prevented by RAS inhibition, or markedly reduced by RAGE blockade......The purpose of this thesis work was to establish an experimental mouse model for studying the pathogenesis and therapy of accelerated atherosclerosis in uremia. Uremia was induced by surgical 5/6 nephrectomy in apolipoprotein E-deficient (apoE-/-) mice and led to development of severe aortic...

  19. Function and Comorbidities of Apolipoprotein E in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Valérie Leduc

    2011-01-01

    Full Text Available Alzheimer's disease (AD—the most common type of dementia among the elderly—represents one of the most challenging and urgent medical mysteries affecting our aging population. Although dominant inherited mutation in genes involved in the amyloid metabolism can elicit familial AD, the overwhelming majority of AD cases, dubbed sporadic AD, do not display this Mendelian inheritance pattern. Apolipoprotein E (APOE, the main lipid carrier protein in the central nervous system, is the only gene that has been robustly and consistently associated with AD risk. The purpose of the current paper is thus to highlight the pleiotropic roles and the structure-function relationship of APOE to stimulate both the functional characterization and the identification of novel lipid homeostasis-related molecular targets involved in AD.

  20. Apolipoprotein B100 analysis in microchip with electrochemical detection

    Institute of Scientific and Technical Information of China (English)

    Cheng Cheng Liu; Yun Liu; Hui Xiang Wang; Yan Bo Qi; Peng Yuan Yang; Bao Hong Liu

    2011-01-01

    Apolipoprotein B100 (apoB-100) is a major protein of the cholesterol-rich low-density lipoprotein (LDL) and reflects a better assessment of total atherogenic burden to the vascular system than LDL. In this work, a simple and sensitive method has been developed to determine picoliter apoB-100s using the PMMA microfluidic chip coupled with electrochemical detection system. This method performs very well with a detectable linear range of 1-800 pg/mL and a detection limit of 1 pg/mL. A real serum sample has further been detected by this microchip-based biosensor. The results show that this kind of method is practicable and has the potential application in clinical analysis and diagnosis.

  1. Hepatosteatosis and estrogen increase apolipoprotein O production in the chicken.

    Science.gov (United States)

    Schmidinger, Barbara; Weijler, Anna M; Schneider, Wolfgang J; Hermann, Marcela

    2016-08-01

    Apolipoprotein O (ApoO) is a recently discovered plasma apolipoprotein that may also play a role in the mitochondrial inner membrane. Possibly due to this complexity, its physiological functions have not been elucidated yet. To gain insight from a non-mammalian experimental system, we have investigated the regulation of ApoO levels in an alternative, well-suited model for studies on lipid metabolism, the chicken. qPCR using specific primer pairs and Western blot analysis with our rabbit anti-chicken ApoO antiserum demonstrated ApoO in the liver of chickens fed a control or a fat-enriched diet, as well as in 2 chicken hepatoma cell lines, LMH cells and the estrogen-responsive LMH-2A cells, under conditions of lipid loading by incubation with BSA-complexed oleic acid. Induced triglyceride accumulation in both the liver and the hepatic cells was associated with significantly increased levels of ApoO mRNA and protein. Furthermore, upon treatment for 24 h with estrogen of the estrogen receptor-expressing LMH-2A cells, quantitative analysis of ApoO transcripts and Western blotting revealed increases of ApoO expression. Finally, upon a single administration of estrogen to roosters that leads to hyperlipidemia, higher hepatic levels of both ApoO transcript and protein were observed within 24 h. Based on these data, we propose that hepatic expression of ApoO is tightly linked not only to diet-induced hepatosteatosis, but also to increased lipoprotein-production induced by, e.g., hormones. The findings support a role of ApoO as an effector of compromised mitochondrial function that likely accompanies the onset of non-alcoholic fatty liver disease. PMID:27126072

  2. Apolipoprotein and lipid abnormalities in chronic liver failure

    Directory of Open Access Journals (Sweden)

    Spósito A.C.

    1997-01-01

    Full Text Available Total serum lipids, as well as apolipoproteins A-I (apo A-I and B (apo B, were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P<0.001. Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P<0.001. However, the reduction of HDL cholesterol (HDLc was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P<0.05. We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver

  3. Overexpression of apolipoprotein AII in transgenic mice converts high density lipoproteins to proinflammatory particles.

    OpenAIRE

    Castellani, L W; Navab, M; Van Lenten, B J; Hedrick, C. C.; Hama, S Y; Goto, A M; Fogelman, A M; Lusis, A J

    1997-01-01

    Previous studies showed that transgenic mice overexpressing either apolipoprotein AI (apoAI) or apolipoprotein AII (apoAII), the major proteins of HDL, exhibited elevated levels of HDL cholesterol, but, whereas the apoAI-transgenic mice were protected against atherosclerosis, the apoAII-transgenic mice had increased lesion development. We now examine the basis for this striking functional heterogeneity. HDL from apoAI transgenics exhibited an enhanced ability to promote cholesterol efflux fro...

  4. A mathematically defined motif for the radial distribution of charged residues on apolipoprotein amphipathic alpha helixes.

    OpenAIRE

    Hazelrig, J B; Jones, M. K.; Segrest, J P

    1993-01-01

    Multiple amphipathic alpha-helical candidate domains have been identified in exchangeable apolipoproteins by sequence analysis and indirect experimental evidence. The distribution of charged residues can differ within and between these apolipoproteins. Segrest et al. (Segrest, J. P., H. DeLoof, J. G. Dohlman, C. G. Brouillette, and G. M. Anantharamaiah. 1990. Proteins. 8:103-117.) argued that these differences are correlated with lipid affinity. A mathematically defined motif for the particul...

  5. Enhanced Diabetes Susceptibility in Community Dwelling Han Elders Carrying the Apolipoprotein E 3/3 Genotype

    OpenAIRE

    Ban, Chun-Xia; Zhong, Li; Wang, Tao; Zhu, Min-jie; Wang, Jing-Hua; Zhang, Zhen-lian; Wang, Zhe; Su, Ning; Liu, Yuan-Yuan; Shi, Yan-chen; Xiao, Shi-fu; Xia LI

    2016-01-01

    Despite Apolipoprotein E (ApoE) being one of the main apolipoproteins in the blood, the association between its genotype and the high cholesterol or blood glucose levels commonly seen in clinical practice is inconclusive. Such research is also lacking in the Han population. The aim of this study was to investigate the association between APOE genotype, diabetes, and plasma glucose and lipid levels. We included 243 community-dwelling elderly residents in this study. Participant APOE genotypes ...

  6. Mass spectral analyses of the two major apolipoproteins of great ape high density lipoproteins

    OpenAIRE

    Puppione, Donald L.; Della Donna, Lorenza; Laganowsky, Arthur D.; Bassilian, Sara; Souda, Puneet; Ryder, Oliver A.; Whitelegge, Julian P.

    2009-01-01

    The two major apolipoproteins associated with human and chimpanzee (Pan troglodytes) high density lipoproteins (HDL) are apoA-I and dimeric apoA-II. Although humans are closely related to great apes, apolipoprotein data do not exist for bonobos (Pan paniscus), western lowland gorillas (Gorilla gorilla gorilla) and the Sumatran orangutans (Pongo abelii). In the absence of any data, other great apes simply have been assumed to have dimeric apoA-II while other primates and most other mammals hav...

  7. Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family

    DEFF Research Database (Denmark)

    Nilsson, Stefan K; Lookene, Aivar; Beckstead, Jennifer A; Gliemann, Jørgen

    2007-01-01

    Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored the ability of apolipoprotein A-V, in most experiments complexed to disks of dimyristoylphosphatidylcholine, to interact with two members of the low densit...... to receptor-covered sensor chips. Our results indicate that apolipoprotein A-V may influence plasma lipid homeostasis by enhancing receptor-mediated endocytosis of triacylglycerol-rich lipoproteins. Udgivelsesdato: 2007-Mar-27......Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored the ability of apolipoprotein A-V, in most experiments complexed to disks of dimyristoylphosphatidylcholine, to interact with two members of the low density...... lipoprotein receptor family, the low density lipoprotein receptor-related protein and the mosaic type-1 receptor, SorLA. Experiments using surface plasmon resonance showed specific binding of both free and lipid-bound apolipoprotein A-V to both receptors. The binding was calcium dependent and was inhibited by...

  8. The formation of hexagonal-shaped InGaN-nanodisk on GaN-nanowire observed in plasma source molecular beam epitaxy

    KAUST Repository

    Ng, Tien Khee

    2014-03-08

    We report on the properties and growth kinetics of defect-free, photoluminescence (PL) efficient mushroom-like nanowires (MNWs) in the form of ~30nm thick hexagonal-shaped InGaN-nanodisk on GaN nanowires, coexisting with the conventional rod-like InGaN-on-GaN nanowires (RNWs) on (111)-silicon-substrate. When characterized using confocal microscopy (CFM) with 458nm laser excitation, while measuring spontaneous-emission at fixed detection wavelengths, the spatial intensity map evolved from having uniform pixelated emission, to having only an emission ring, and then a round emission spot. This corresponds to the PL emission with increasing indium composition; starting from emission mainly from the RNW, and then the 540 nm emission from one MNWs ensemble, followed by the 590 nm emission from a different MNW ensemble, respectively. These hexagonal-shaped InGaN-nano-disks ensembles were obtained during molecular-beam-epitaxy (MBE) growth. On the other hand, the regular rod-like InGaN-on-GaN nanowires (RNWs) were emitting at a shorter peak wavelength of 490 nm. While the formation of InGaN rod-like nanowire is well-understood, the formation of the hexagonal-shaped InGaN-nanodisk-on-GaN-nanowire requires further investigation. It was postulated to arise from the highly sensitive growth kinetics during plasma-assisted MBE of InGaN at low temperature, i.e. when the substrate temperature was reduced from 800 °C (GaN growth) to <600 °C (InGaN growth), during which sparsely populated metal-droplet formation prevails and further accumulated more indium adatoms due to a higher cohesive bond between metallic molecules. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

  9. Apolipoprotein C-II Adopts Distinct Structures in Complex with Micellar and Submicellar Forms of the Amyloid-Inhibiting Lipid-Mimetic Dodecylphosphocholine.

    Science.gov (United States)

    Ryan, Timothy M; Griffin, Michael D W; McGillivray, Duncan J; Knott, Robert B; Wood, Kathleen; Masters, Colin L; Kirby, Nigel; Curtain, Cyril C

    2016-01-01

    The formation of amyloid deposits is a common feature of a broad range of diseases, including atherosclerosis, Alzheimer's disease, and Parkinson's disease. The basis and role of amyloid deposition in the pathogenesis of these diseases is still being defined, however an interesting feature of amyloidogenic proteins is that the majority of the pathologically associated proteins are involved in lipid homeostasis, be it in lipid transport, incorporation into membranes, or the regulation of lipid pathways. Thus, amyloid-forming proteins commonly bind lipids, and lipids are generally involved in the proper folding of these proteins. However, understanding of the basis for these lipid-related aspects of amyloidogenesis is lacking. Thus, we have used the apolipoprotein C-II amyloid model system in conjunction with x-ray and neutron scattering analyses to address this problem. Apolipoprotein C-II is a well-studied model system of systemic amyloid fibril formation, with a clear and well-defined pathway for fibril formation, where the effects of lipid interaction are characterized, particularly for the lipid mimetic dodecylphosphocholine. We show that the micellar state of an inhibitory lipid can have a very significant effect on protein conformation, with micelles stabilizing a particular α-helical structure, whereas submicellar lipids stabilize a very different dimeric, α-helical structure. These results indicate that lipids may have an important role in the development and progression of amyloid-related diseases. PMID:26745412

  10. Changes in plasma apolipoproteins following whole-body irradiation in rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Feliste, R. (INSERM, Toulouse, France); Dousset, N.; Carton, M.; Douste-Blazy, L.

    1981-09-01

    Male New Zealand white rabbits were whole-body-irradiated with a linear electron accelerator at 800 rad (LD/sub 50/ in 30 days). This treatment induced a pronounced hypertriglyceridemia. The apoprotein composition of very low density lipoproteins (VLDL, d < 1.006 g/ml) and high-density lipoproteins (HDL, d = 1.063 - 1.21 g/ml) from irradiated rabbits was studied and compared to those of normal rabbits. Significant changes were observed in both very low density apolipoproteins and high-density apolipoproteins. (1) In the VLDL fraction from irradiated rabbits, there appeared in high proportion two apolipoproteins with electrophoretic mobility in urea/polyacrylamide gels similar to apoA-I and A-II but which were distinctly different in their apparent molecular weights, their isoelectric points, and their amino acid composition from these latter proteins. These proteins had apparent molecular weights of about 10,000. They focused into three bands with pI values of 6.1, 6.4, and 6.6. Their amino acid composition was characterized by a very low content of threonine and serine and a high content of aspartic acid, glycine, alanine, and arginine. In addition, a marked increase of an apolipoprotein with an apparent molecular weight of about 43,000 and with an amino acid composition similar to rat apoA-IV was also observed in rabbit VLDL after irradiation. Apolipoprotein C constituents with slowmobility decreased significantly. (2) The irradiated rabbit HDL apolipoproteins showed an important increase of the proteins with molecular weight 10,000 and isoelectric points 6.1, 6.4, and 6.6. Compared to normal rabbit HDL apolipoproteins, a significant decrease of apoA-IV occurred. These modifications were also observed with lower radiation doses (200 and 400 rad).

  11. Gender and age specific differences in the kinetic behavior of TRL, IDL and LDL apolipoprotein B-100 and HDL apolipoprotein A-I

    Science.gov (United States)

    Gender specific differences in lipid and lipoprotein profile, predominantly higher LDL-C, VLDL-C and TG, and lower HDL-C levels have been observed in males compared to females. These differences are influenced by menopausal status and age. To investigate mechanism(s) involved, apolipoprotein (apo) B...

  12. Apolipoprotein A-II Influences Apolipoprotein E-Linked Cardiovascular Disease Risk in Women with High Levels of HDL Cholesterol and C-Reactive Protein

    NARCIS (Netherlands)

    Corsetti, James P.; Bakker, Stephan J. L.; Sparks, Charles E.; Dullaart, Robin P. F.

    2012-01-01

    Background: In a previous report by our group, high levels of apolipoprotein E (apoE) were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP) in the setting of both low (designated as HR1 subjects) and high (designated as

  13. Measurement of the intrinsic damping constant in individual nanodisks of Y{sub 3}Fe{sub 5}O{sub 12} and Y{sub 3}Fe{sub 5}O{sub 12}|Pt

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, C.; Loubens, G. de, E-mail: oklein@cea.fr, E-mail: gregoire.deloubens@cea.fr; Klein, O., E-mail: oklein@cea.fr, E-mail: gregoire.deloubens@cea.fr [Service de Physique de l’État Condensé (CNRS URA 2464), CEA Saclay, 91191 Gif-sur-Yvette (France); Naletov, V. V. [Service de Physique de l’État Condensé (CNRS URA 2464), CEA Saclay, 91191 Gif-sur-Yvette (France); Unité Mixte de Physique CNRS/Thales and Université Paris Sud 11, 1 Ave. Fresnel, 91767 Palaiseau (France); Institute of Physics, Kazan Federal University, Kazan 420008 (Russian Federation); D' Allivy Kelly, O.; Anane, A.; Bernard, R.; Jacquet, E.; Bortolotti, P.; Cros, V. [Unité Mixte de Physique CNRS/Thales and Université Paris Sud 11, 1 Ave. Fresnel, 91767 Palaiseau (France); Prieto, J. L. [Instituto de Sistemas Optoelectrónicos y Microtecnología (UPM), Madrid 28040 (Spain); Muñoz, M. [Instituto de Microelectrónica de Madrid (CNM, CSIC), Madrid 28760 (Spain)

    2014-04-14

    We report on an experimental study on the spin-waves relaxation rate in two series of nanodisks of diameter ϕ=300, 500, and 700 nm, patterned out of two systems: a 20 nm thick yttrium iron garnet (YIG) film grown by pulsed laser deposition either bare or covered by 13 nm of Pt. Using a magnetic resonance force microscope, we measure precisely the ferromagnetic resonance linewidth of each individual YIG and YIG|Pt nanodisks. We find that the linewidth in the nanostructure is sensibly smaller than the one measured in the extended film. Analysis of the frequency dependence of the spectral linewidth indicates that the improvement is principally due to the suppression of the inhomogeneous part of the broadening due to geometrical confinement, suggesting that only the homogeneous broadening contributes to the linewidth of the nanostructure. For the bare YIG nano-disks, the broadening is associated to a damping constant α=4 × 10{sup −4}. A threefold increase of the linewidth is observed for the series with Pt cap layer, attributed to the spin pumping effect. The measured enhancement allows to extract the spin mixing conductance found to be G{sub ↑↓}=1.55 × 10{sup 14} Ω{sup −1} m{sup −2} for our YIG(20nm)|Pt interface, thus opening large opportunities for the design of YIG based nanostructures with optimized magnetic losses.

  14. Solution Conditions Affect the Ability of the K30D Mutation To Prevent Amyloid Fibril Formation by Apolipoprotein C-II: Insights from Experiments and Theoretical Simulations.

    Science.gov (United States)

    Mao, Yu; Todorova, Nevena; Zlatic, Courtney O; Gooley, Paul R; Griffin, Michael D W; Howlett, Geoffrey J; Yarovsky, Irene

    2016-07-12

    Apolipoproteins form amphipathic helical structures that bind lipid surfaces. Paradoxically, lipid-free apolipoproteins display a strong propensity to form cross-β structure and self-associate into disease-related amyloid fibrils. Studies of apolipoprotein C-II (apoC-II) amyloid fibrils suggest that a K30-D69 ion pair accounts for the dual abilities to form helix and cross-β structure. Consistent with this is the observation that a K30D mutation prevents fibril formation under standard fibril forming conditions. However, we found that fibril formation by K30D apoC-II proceeded readily at low pH and a higher salt or protein concentration. Structural analysis demonstrated that K30D apoC-II fibrils at pH 7 have a structure similar to that of the wild-type fibrils but are less stable. Molecular dynamics simulations of the wild-type apoC-II fibril model at pH 7 and 3 showed that the loss of charge on D69 at pH 3 leads to greater separation between residues K30 and D69 within the fibril with a corresponding reduction in β-strand content around residue 30. In contrast, in simulations of the K30D mutant model at pH 7 and 3, residues D30 and D69 moved closer at pH 3, accompanied by an increase in β-strand content around residue 30. The simulations also demonstrated a strong dominance of inter- over intramolecular contacts between ionic residues of apoC-II and suggested a cooperative mechanism for forming favorable interactions between the individual strands under different conditions. These observations demonstrate the important role of the buried K30-D69 ion pair in the stability and solution properties of apoC-II amyloid fibrils. PMID:27311794

  15. Solubility engineering and crystallization of human apolipoprotein D

    Science.gov (United States)

    Nasreen, Amber; Vogt, Martin; Kim, Hyun Jin; Eichinger, Andreas; Skerra, Arne

    2006-01-01

    Human apolipoprotein D (ApoD) is a physiologically important member of the lipocalin protein family that was discovered as a peripheral subunit of the high-density lipoprotein (HDL) but is also abundant in other body fluids and organs, including neuronal tissue. Although it has been possible to produce functional ApoD in the periplasm of Escherichia coli and to demonstrate its ligand-binding activity for progesterone and arachidonic acid, the recombinant protein suffers from a pronounced tendency to aggregate and to adsorb to vessel surfaces as well as chromatography matrices, thus hampering further structural investigation. Here, we describe a systematic mutagenesis study directed at presumably exposed hydrophobic side chains of the unglycosylated recombinant protein. As a result, one ApoD mutant with just three new amino acid substitutions—W99H, I118S, and L120S—was identified, which exhibits the following features: (1) improved yield upon periplasmic biosynthesis in E. coli, (2) elution as a monomeric protein from a gel permeation chromatography column, and (3) unchanged binding activity for its physiological ligands. In addition, the engineered ApoD was successfully crystallized (space group I4 with unit cell parameters a = 75.1 Å, b = 75.1 Å, c = 166.0 Å, α = β = γ = 90°), thus demonstrating its conformationally homogeneous behavior and providing a basis for the future X-ray structural analysis of this functionally still puzzling protein. PMID:16322568

  16. Glucose Regulates the Expression of the Apolipoprotein A5 Gene

    Energy Technology Data Exchange (ETDEWEB)

    Fruchart, Jamila; Nowak, Maxime; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Moitrot, Emmanuelle; Rommens, Corinne; Pennacchio, Len A.; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2008-04-07

    The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.

  17. Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation

    DEFF Research Database (Denmark)

    Bartels, Emil D; Ploug, Thorkil; Størling, Joachim;

    2014-01-01

    Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design....... In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apo......B transgenic mice accumulated 28% less triglycerides in skeletal myocytes after one year of fat-feeding as compared with WT mice (32 ± 5, n = 10 vs. 44 ± 4 nmol/mg ww, n = 13, p = 0.04). Moreover, expression of human apoB in fat-fed mice was associated with 32% (p = 0.02) and 37% (p = 0.01) lower plasma...

  18. Optimisation and evaluation of restriction fragment length polimorfism method for apolipoprotein E

    Directory of Open Access Journals (Sweden)

    Drljević Nevena

    2014-01-01

    Full Text Available Introduction. Apolipoprotein E gene polymorphism is characterized by the presence of three common alleles, e2, e3 and e4, which encode three isoforms of apolipoprotein E in plasma E2, E3 and E4. Genetic polymorphisms of apolipoprotein E gene are predictive markers for the development of numerous disorders of lipid metabolism, already proven in a large number of clinical trials. This study was aimed at assessing the success rate of restriction fragment length polymorphism method for the detections of genes coding for isoenzymes E2, E3 and E4. Material and Methods. Deoxyribonucleic acid, used in this study, was extracted from blood by standard procedure using chloroform and phenol. The polymerase chain reaction method was used to amplify the coding sequence of fourth exon of the apolipoprotein E gene. Amplification products were digested with HhaI. The fragments obtained were separated by electrophoresis and visualized with ultraviolet light. Results. Our results showed that the restriction fragment length polymorphism method is optimal for detection of apolipoprotein E polymorphisms. The restriction enzyme HhaI achieved the cleavage of the gene on the specific loci, directly depend of presence or absence of mutations at positions 112 and 158, of different alleles. Conclusion. This method enables simple, rapid and efficient analysis of restriction fragment length polymorphisms, directly determining the patient’s genotype.

  19. Apolipoprotein A1 in channel catfish: Transcriptional analysis, antimicrobial activity, and efficacy as plasmid DNA immunostimulant against Aeromonas hydrophila infection

    Science.gov (United States)

    The objectives of this study were to: 1) determine transcriptional profiles of apolipoprotein A1 (ApoA1) in collected channel catfish tissues after infection with A. hydrophila by bath immersion; 2) investigate whether recombinant channel catfish apolipoprotein A1 produced in E. coli expression syst...

  20. Apolipoprotein A-I deficiency due to a codon 84 nonsense mutation of the apolipoprotein A-I gene

    International Nuclear Information System (INIS)

    The molecular genetic defect of a female patient with apolipoprotein A-I (apoA-I) deficiency and premature atherosclerosis was examined. Her parents were first cousins. Her plasma density fraction from 1.063 to 1.21 g/ml contained no apoA-I on SDS/PAGE and no measurable high density lipoprotein cholesterol. Southern blot hybridization showed no gross abnormality to be present in the patient's apoA-I gene and homozygosity for a haplotype of restriction fragment length polymorphisms in the apoA-I gene region. Sequencing after amplification by PCR revealed a codon 84 nonsense mutation (CAG → TAG, Gln → stop) of exon 4 and a codon 37 missense mutation (GCC→ ACC, Ala → Thr) of exon 3 in the patient's apoA-I gene. The data from dot-blot hybridization with allele-specific oligonucleotide probes indicated that she was homozygous for the apoA-I gene with regard to the two mutations. The codon 37 missense mutation was also detected in the apoA-I gene of 6 out of 60 controls, who all had normal levels of apoA-I and high density lipoprotein cholesterol, suggesting that the missense mutation is polymorphic and not associated with apoA-I deficiency. These finding indicate that homozygosity for the apoA-I gene with codon 84 nonsense mutation causes the deficiency of apoA-I and of high density lipoprotein cholesterol in the patient

  1. Conformational and aggregation properties of the 1-93 fragment of apolipoprotein A-I

    DEFF Research Database (Denmark)

    Petrlova, Jitka; Bhattacherjee, Arnab; Boomsma, Wouter Krogh;

    2014-01-01

    Several disease-linked mutations of apolipoprotein A-I, the major protein in high-density lipoprotein (HDL), are known to be amyloidogenic, and the fibrils often contain N-terminal fragments of the protein. Here, we present a combined computational and experimental study of the fibril-associated ......Several disease-linked mutations of apolipoprotein A-I, the major protein in high-density lipoprotein (HDL), are known to be amyloidogenic, and the fibrils often contain N-terminal fragments of the protein. Here, we present a combined computational and experimental study of the fibril...... these conformational shifts match well with the effects of these mutations in thioflavin T fluorescence and transmission electron microscopy experiments. Together, our results point to molecular mechanisms that may have a key role in disease-linked aggregation of apolipoprotein A-I....

  2. Insulin resistance, dyslipidemia, and apolipoprotein E interactions as mechanisms in cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Salameh, Therese S; Rhea, Elizabeth M; Banks, William A; Hanson, Angela J

    2016-09-01

    An increased risk for Alzheimer's disease is associated with dyslipidemia and insulin resistance. A separate literature shows the genetic risk for developing Alzheimer's disease is strongly correlated to the presence of the E4 isoform of the apolipoprotein E carrier protein. Understanding how apolipoprotein E carrier protein, lipids, amyloid β peptides, glucose, central nervous system insulin, and peripheral insulin interact with one another in Alzheimer's disease is an area of increasing interest. Here, we will review the evidence relating apolipoprotein E carrier protein, lipids, and insulin action to Alzheimer's disease and Aβ peptides and then propose mechanisms as to how these factors might interact with one another to impair cognition and promote Alzheimer's disease. PMID:27470930

  3. Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lasrich, Dorothee; Bartelt, Alexander [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Grewal, Thomas, E-mail: thomas.grewal@sydney.edu.au [Faculty of Pharmacy A15, The University of Sydney, Sydney, NSW 2006 (Australia); Heeren, Joerg, E-mail: heeren@uke.de [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany)

    2015-09-10

    Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not differentiation.

  4. Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders.

    Science.gov (United States)

    Mahley, Robert W

    2016-07-01

    Apolipoprotein (apo) E was initially described as a lipid transport protein and major ligand for low density lipoprotein (LDL) receptors with a role in cholesterol metabolism and cardiovascular disease. It has since emerged as a major risk factor (causative gene) for Alzheimer's disease and other neurodegenerative disorders. Detailed understanding of the structural features of the three isoforms (apoE2, apoE3, and apoE4), which differ by only a single amino acid interchange, has elucidated their unique functions. ApoE2 and apoE4 increase the risk for heart disease: apoE2 increases atherogenic lipoprotein levels (it binds poorly to LDL receptors), and apoE4 increases LDL levels (it binds preferentially to triglyceride-rich, very low density lipoproteins, leading to downregulation of LDL receptors). ApoE4 also increases the risk for neurodegenerative diseases, decreases their age of onset, or alters their progression. ApoE4 likely causes neurodegeneration secondary to its abnormal structure, caused by an interaction between its carboxyl- and amino-terminal domains, called domain interaction. When neurons are stressed or injured, they synthesize apoE to redistribute cholesterol for neuronal repair or remodeling. However, because of its altered structure, neuronal apoE4 undergoes neuron-specific proteolysis, generating neurotoxic fragments (12-29 kDa) that escape the secretory pathway and cause mitochondrial dysfunction and cytoskeletal alterations, including tau phosphorylation. ApoE4-associated pathology can be prevented by small-molecule structure correctors that block domain interaction by converting apoE4 to a molecule that resembles apoE3 both structurally and functionally. Structure correctors are a potential therapeutic approach to reduce apoE4 pathology in both cardiovascular and neurological disorders. PMID:27277824

  5. IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.

    Directory of Open Access Journals (Sweden)

    Polyxeni T Mantani

    Full Text Available IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apoE deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.

  6. Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

    International Nuclear Information System (INIS)

    Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not differentiation.

  7. An abundant dysfunctional apolipoprotein A1 in human atheroma.

    Science.gov (United States)

    Huang, Ying; DiDonato, Joseph A; Levison, Bruce S; Schmitt, Dave; Li, Lin; Wu, Yuping; Buffa, Jennifer; Kim, Timothy; Gerstenecker, Gary S; Gu, Xiaodong; Kadiyala, Chandra S; Wang, Zeneng; Culley, Miranda K; Hazen, Jennie E; Didonato, Anthony J; Fu, Xiaoming; Berisha, Stela Z; Peng, Daoquan; Nguyen, Truc T; Liang, Shaohong; Chuang, Chia-Chi; Cho, Leslie; Plow, Edward F; Fox, Paul L; Gogonea, Valentin; Tang, W H Wilson; Parks, John S; Fisher, Edward A; Smith, Jonathan D; Hazen, Stanley L

    2014-02-01

    Recent studies have indicated that high-density lipoproteins (HDLs) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma are dysfunctional and are extensively oxidized by myeloperoxidase (MPO). In vitro oxidation of either apoA1 or HDL particles by MPO impairs their cholesterol acceptor function. Here, using phage display affinity maturation, we developed a high-affinity monoclonal antibody that specifically recognizes both apoA1 and HDL that have been modified by the MPO-H2O2-Cl(-) system. An oxindolyl alanine (2-OH-Trp) moiety at Trp72 of apoA1 is the immunogenic epitope. Mutagenesis studies confirmed a critical role for apoA1 Trp72 in MPO-mediated inhibition of the ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol acceptor activity of apoA1 in vitro and in vivo. ApoA1 containing a 2-OH-Trp72 group (oxTrp72-apoA1) is in low abundance within the circulation but accounts for 20% of the apoA1 in atherosclerosis-laden arteries. OxTrp72-apoA1 recovered from human atheroma or plasma is lipid poor, virtually devoid of cholesterol acceptor activity and demonstrated both a potent proinflammatory activity on endothelial cells and an impaired HDL biogenesis activity in vivo. Elevated oxTrp72-apoA1 levels in subjects presenting to a cardiology clinic (n = 627) were associated with increased cardiovascular disease risk. Circulating oxTrp72-apoA1 levels may serve as a way to monitor a proatherogenic process in the artery wall. PMID:24464187

  8. Apolipoprotein E isoform-specific effects on lipoprotein receptor processing.

    Science.gov (United States)

    Bachmeier, Corbin; Shackleton, Ben; Ojo, Joseph; Paris, Daniel; Mullan, Michael; Crawford, Fiona

    2014-12-01

    Recent findings indicate an isoform-specific role for apolipoprotein E (apoE) in the elimination of beta-amyloid (Aβ) from the brain. ApoE is closely associated with various lipoprotein receptors, which contribute to Aβ brain removal via metabolic clearance or transit across the blood–brain barrier (BBB). These receptors are subject to ectodomain shedding at the cell surface, which alters endocytic transport and mitigates Aβ elimination. To further understand the manner in which apoE influences Aβ brain clearance, these studies investigated the effect of apoE on lipoprotein receptor shedding. Consistent with prior reports, we observed an increased shedding of the low-density lipoprotein receptor (LDLR) and the LDLR-related protein 1 (LRP1) following Aβ exposure in human brain endothelial cells. When Aβ was co-treated with each apoE isoform, there was a reduction in Aβ-induced shedding with apoE2 and apoE3, while lipoprotein receptor shedding in the presence of apoE4 remained increased. Likewise, intracranial administration of Aβ to apoE-targeted replacement mice (expressing the human apoE isoforms) resulted in an isoform-dependent effect on lipoprotein receptor shedding in the brain (apoE4 > apoE3 > apoE2). Moreover, these results show a strong inverse correlation with our prior work in apoE transgenic mice in which apoE4 animals showed reduced Aβ clearance across the BBB compared to apoE3 animals. Based on these results, apoE4 appears less efficient than other apoE isoforms in regulating lipoprotein receptor shedding, which may explain the differential effects of these isoforms in removing Aβ from the brain. PMID:25015123

  9. Plasma Apolipoprotein-M (ApoM) Response to a Circuit Resistance Training Program

    OpenAIRE

    Abbass Ghanbari-Niaki

    2013-01-01

    Apolipoprotein M (Apo-M) is a human novel protein of apolipoprotein classes and highly expressed in liver and kidney tissues. ApoM is mainly associated with high-density lipoprotein (HDL), and act as a chaperone for sphingosine-1-phosphate (S1P), promotes mobilization of cellular cholesterol, formation of larger-size of pre β-HDL, and a new biomarker in sepsis. The level of apoM in plasma/serum is affected by several factors such as pregnancy, hyperglycemia, plasma leptin concentration, obe...

  10. Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins

    DEFF Research Database (Denmark)

    Varkey, Jobin; Isas, Jose Mario; Mizuno, Naoko;

    2010-01-01

    Synucleins and apolipoproteins have been implicated in a number of membrane and lipid trafficking events. Lipid interaction for both types of proteins is mediated by 11 amino acid repeats that form amphipathic helices. This similarity suggests that synucleins and apolipoproteins might have...... amphipathic helices alone. Moreover, we frequently observed that a-synuclein caused membrane structures that had the appearance of nascent budding vesicles. The ability to function as a minimal machinery for vesicle budding agrees well with recent findings that a-synuclein plays a role in vesicle trafficking...

  11. Self-assembling polymer micelle/clay nanodisk/doxorubicin hybrid injectable gels for safe and efficient focal treatment of cancer.

    Science.gov (United States)

    Nagahama, Koji; Kawano, Daichi; Oyama, Naho; Takemoto, Ayaka; Kumano, Takayuki; Kawakami, Junji

    2015-03-01

    The purpose of this study was to fabricate a safe and effective doxorubicin (DOX)-delivery system for focal cancer chemotherapy. A novel biodegradable injectable gel was developed through self-assembly of poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymer micelles, clay nanodisks (CNDs), and DOX. We discovered that DOX loaded in the hybrid gels acts as an anticancer drug and as a building block to organize new gel networks. Accordingly, long-term sustained release of DOX from hybrid injectable gels without initial burst release was achieved. Moreover, it was revealed that the DOX incorporated into gel networks controls its own release profile. This hybrid injectable gel is a self-controlled drug release system, which is a novel concept in controlled drug release. Importantly, a single injection of PLGA-PEG-PLGA/CND/DOX hybrid gel provides long-term sustained antitumor activity in vivo against human xenograft tumors in mice, suggesting the potential of hybrid gels as a valuable local DOX-delivery platform for cancer focal therapy. PMID:25645815

  12. Effects of formation of mini-bands in two-dimensional array of silicon nanodisks with SiC interlayer for quantum dot solar cells

    International Nuclear Information System (INIS)

    A sub-10 nm, high-density, periodic silicon nanodisk (Si-ND) array with a SiC interlayer has been fabricated using a new top-down process that involves a 2D array of a bio-template etching mask and damage-free neutral beam etching. Optical and electrical measurements were carried out to clarify the formation of mini-bands due to wavefunction coupling. We found that the SiC interlayer could enhance the optical absorption coefficient in the layer of Si-NDs due to the stronger coupling of wavefunctions. Theoretical simulation also indicated that wavefunction coupling was effectively enhanced in Si-NDs with a SiC interlayer, which precisely matched the experimental results. Furthermore, the I–V properties of a 2D array of Si-NDs with a SiC interlayer were studied through conductive AFM measurements, which indicated conductivity in the structure was enhanced by strong lateral electronic coupling between neighboring Si-NDs. We confirmed carrier generation and less current degradation in the structure due to high photon absorption and conductivity by inserting the Si-NDs into p–i–n solar cells. (paper)

  13. Low-Temperature Facile Synthesis of Sb-Doped p-Type ZnO Nanodisks and Its Application in Homojunction Light-Emitting Diode.

    Science.gov (United States)

    Baek, Sung-Doo; Biswas, Pranab; Kim, Jong-Woo; Kim, Yun Cheol; Lee, Tae Il; Myoung, Jae-Min

    2016-05-25

    This study explores low-temperature solution-process-based seed-layer-free ZnO p-n homojunction light-emitting diode (LED). In order to obtain p-type ZnO nanodisks (NDs), antimony (Sb) was doped into ZnO by using a facile chemical route at 120 °C. The X-ray photoelectron spectra indicated the presence of (SbZn-2VZn) acceptor complex in the Sb-doped ZnO NDs. Using these NDs as freestanding templates, undoped n-type ZnO nanorods (NRs) were epitaxially grown at 95 °C to form ZnO p-n homojunction. The homojunction with a turn-on voltage of 2.5 V was found to be significantly stable up to 100 s under a constant voltage stress of 5 V. A strong orange-red emission was observed by the naked eye under a forward bias of 5 V. The electroluminescence spectra revealed three major peaks at 400, 612, and 742 nm which were attributed to the transitions from Zni to VBM, from Zni to Oi, and from VO to VBM, respectively. The presence of these deep-level defects was confirmed by the photoluminescence of ZnO NRs. This study paves the way for future applications of ZnO homojunction LEDs using low-temperature and low-cost solution processes with the controlled use of native defects. PMID:27160161

  14. Hyperglycemia-induced hyperinsulinemia acutely lowers plasma apolipoprotein B but not lipoprotein (a) in man

    NARCIS (Netherlands)

    Riemens, SC; Ligtenberg, JJM; Dullaart, RPF

    1997-01-01

    Acute hyperinsulinemia lowers plasma apolipoprotein B (apo B) and triglycerides by suppressing hepatic lipoprotein secretion and probably by enhancing catabolism of triglyceride-rich lipoproteins, but the effect of acute hyperinsulinemia on the plasma lipoprotein(a) (Lp(a)) level is unclear. We meas

  15. Trimerization of apolipoprotein A-I retards plasma clearance and preserves antiatherosclerotic properties

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Laurberg, Jacob Marsvin; Andersen, Mikkel Holmen;

    2008-01-01

    An increased plasma level of the major high-density lipoprotein (HDL) component, apolipoprotein A-I (apoA-I) is the aim of several therapeutic strategies for combating atherosclerotic disease. HDL therapy by direct intravenous administration of apoA-I is a plausible way; however, a fast renal...

  16. Mutation in apolipoprotein B associated with hypobetalipoproteinemia despite decreased binding to the low density lipoprotein receptor

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan Skov;

    2005-01-01

    Mutations in apolipoprotein B (APOB) may reduce binding of low density lipoprotein (LDL) to the LDL receptor and cause hypercholesterolemia. We showed that heterozygotes for a new mutation in APOB have hypobetalipoproteinemia, despite a reduced binding of LDL to the LDL receptor. APOB R3480P...

  17. Apolipoprotein D is associated with long-term outcome in patients with schizophrenia

    DEFF Research Database (Denmark)

    Hansen, T; Hemmingsen, R P; Wang, A G;

    2006-01-01

    Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second, gene...

  18. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Bentzen, Joan; Poulsen, Pernille; Vaag, Allan; Fenger, Mogens

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI R...... five polymorphisms was seen in the dizygotic twins. The effect of the polymorphisms on lipid and glucose parameters could be mediated through linkage to genes with known effect on glucose metabolism or through free fatty acids exerting their effect on glucose metabolism.......The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco......RI RFLP) were established using polymerase chain reaction and restriction enzyme digests. The effect of genotypes on lipid levels and on glucose, insulin, and HOMA (i.e., calculated parameters of beta-cell function and insulin resistance) was assessed by multivariate analyses of variance correcting for...

  19. The Apolipoprotein E/CI/CII Gene Cluster and Late-Onset Alzheimer Disease

    OpenAIRE

    Yu, Chang-En; Payami, Haydeh; Olson, Jane M.; Boehnke, Michael; Wijsman, Ellen M; Orr, Harry T.; Kukull, Walter A.; Goddard, Katrina A B; Nemens, Ellen; White, June A.; Alonso, M. Elisa; Taylor, Todd D.; Ball, Melvyn J.; Kaye, Jeffrey; Morris, John

    1994-01-01

    The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset

  20. Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

    International Nuclear Information System (INIS)

    Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

  1. Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice

    Czech Academy of Sciences Publication Activity Database

    Dolejší, Eva; Liraz, O.; Rudajev, Vladimír; Zimčík, Pavel; Doležal, Vladimír; Michaelson, D. M.

    Roč. 136, č. 3 ( 2016 ), s. 503-509. ISSN 0022-3042 R&D Projects: GA MŠk(CZ) LH13269 Institutional support: RVO:67985823 Keywords : acetylcholine release * Alzheimer's disease (AD) * apolipoprotein E4 (apoE4) * hippocampus Subject RIV: FH - Neurology Impact factor: 4.281, year: 2014

  2. Plasma apolipoprotein M responses to statin and fibrate administration in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Kappelle, Paul J. W. H.; Ahnstrom, Josefin; Dikkeschei, Bert D.; de Vries, Rindert; Sluiter, Wim J.; Wolffenbuttel, Bruce H. R.; van Tol, Arie; Nielsen, Lars Bo; Dahlback, Bjorn; Dullaart, Robin P. F.

    2010-01-01

    Purpose: Plasma apolipoprotein M (apoM) is potentially anti-atherogenic, and has been found to be associated positively with plasma total, LDL and HDL cholesterol in humans. ApoM may, therefore, be intricately related to cholesterol metabolism. Here, we determined whether plasma apoM is affected by

  3. Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Gorm Boje;

    2007-01-01

    Apolipoprotein B (apoB) levels predict fatal myocardial infarction. Whether apoB also predicts nonfatal ischemic cardiovascular events is unclear. We tested the following hypotheses: apoB predicts ischemic cardiovascular events, and apoB is a better predictor of ischemic cardiovascular events tha...

  4. PLASMA-LIPOPROTEINS AND RENAL APOLIPOPROTEINS IN RATS WITH CHRONIC ADRIAMYCIN NEPHROSIS

    NARCIS (Netherlands)

    JOLES, JA; VANTOL, A; JANSEN, EHJM; KOOMANS, HA; RABELINK, TJ; VANGOOR, H

    1993-01-01

    The relation between plasma lipoprotein composition and renal apolipoprotein deposition was studied in nephrotic rats in which stable renal function had been monitored for 7 months after a single low dose of adriamycin (ADR, 3 mg/kg). Proteinuria was observed 3 weeks after ADR and increased progress

  5. Apolipoprotein B genetic variants modify the response to fenofibrate: a GOLDN study

    Science.gov (United States)

    Hypertriglyceridemia, defined as a triglyceride measurement > 150 mg/dl, occurs in up to 34% of adults. Fenofibrate is a commonly used drug to treat hypertriglyceridemia, but response to fenofibrate varies considerably among individuals. We sought to determine if genetic variation in apolipoprotein...

  6. Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

    Energy Technology Data Exchange (ETDEWEB)

    Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-10-01

    Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

  7. APOLIPOPROTEIN E GENE POLYMORPHISMS ARE NOT ASSOCIATED WITH DIABETIC RETINOPATHY: THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY

    Science.gov (United States)

    PURPOSE: Polymorphism of the apolipoprotein E (APOE) gene has been associated with dyslipidemia and cardiovascular disease. This study examines the association of APOE polymorphisms and diabetic retinopathy. DESIGN: Population-based cross-sectional study. METHODS: We studied 1,398 people aged 49 to ...

  8. Effect of apolipoprotein a-I complex with tetrahydrocortisone on protein biosynthesis and glucose absorption by rat hepatocytes.

    Science.gov (United States)

    Sumenkova, D V; Knyazev, R A; Guschya, R S; Polyakov, L M; Panin, L E

    2009-08-01

    We studied the effect of apolipoprotein A-I-tetrahydrocortisone complex on (14)C glucose absorption and lactate accumulation and on the rate of protein biosynthesis in isolated rat hepatocytes. The presence of apolipoprotein A-I-tetrahydrocortisone complex in the incubation medium increased absorption of labeled glucose by hepatocytes by 52%, while lactate content in the conditioning medium increased 4-fold. The rate of protein biosynthesis increased by 80% in comparison with control cells. It is hypothesized that the increase in protein biosynthesis rate in hepatocytes under the effect of apolipoprotein A-I-tetrahydrocortisone complex is due to stimulation of energy metabolism, specifically, of its glycolytic component. PMID:20027330

  9. Construction of a biotinylated cameloid-like antibody for lable-free detection of apolipoprotein B-100.

    Science.gov (United States)

    Li, Henan; Yan, Junrong; Ou, Weijun; Liu, Hong; Liu, Songqin; Wan, Yakun

    2015-02-15

    Nanobodies (Nbs), also known as the variable domain of the heavy-chain-only antibody (VHH), are single-domain antigen-binding fragments derived from heavy-chain antibodies that occur naturally in sera of camelids. Due to their unique properties of small size (15 kD), intrinsic stability, high affinity and specificity, Nbs are suitable for detecting clinical relevant antigens. Apolipoprotein B-100 (ApoB-100) is a highly predictive marker for coronary artery disease (CAD), which is frequently detected in clinical diagnosis. Herein, we successfully obtained anti-ApoB-100 Nbs for the first time and further fabricated a label-free and sensitive immunosensor for ApoB-100 based on isolated anti-ApoB-100 nanobody (Nb) using the electrochemical impedance spectroscopy (EIS) technique. We have generated an immunized phage display library against ApoB-100 and isolated four anti-ApoB-100 Nbs with high affinity and stability. The Nb with the highest affinity was biotinylated based on in vivo BirA system. Further, we developed a label-free electrochemical impedance immunosensor for ApoB-100 using this anti-ApoB-100 Nb. The attachment of ApoB-100 onto the anti-ApoB-100 Nb-immobilized sensing layer led to the increased electron-transfer resistance, which was proportional to ApoB-100 concentration in the range from 0.05 to 5 ng mL(-1) with a detection limit of 0.03 ng mL(-1). This proposed immunosensor revealed high specificity to detect ApoB-100, acceptable intra-assay precision and good stability, functioning as a feasible technique for CAD diagnosis. PMID:25203942

  10. Plasma proteome changes in cardiovascular disease patients: novel isoforms of apolipoprotein A1

    Directory of Open Access Journals (Sweden)

    Oravec Milan

    2011-06-01

    Full Text Available Abstract Background The aim of this proteomic study was to look for changes taking place in plasma proteomes of patients with acute myocardial infarction (AMI, unstable angina pectoris (UAP, and stable angina pectoris (SAP. Methods Depleted plasma proteins were separated by 2D SDS-PAGE (pI 4-7, and proteomes were compared using Progenesis SameSpots statistical software. Proteins were identified by nanoLC-MS/MS. Proteins were quantified using commercial kits. Apolipoprotein A1 was studied using 1D and 2D SDS-PAGE, together with western blotting. Results Reciprocal comparison revealed 46 unique, significantly different spots; proteins in 34 spots were successfully identified and corresponded to 38 different proteins. Discrete comparisons of patient groups showed 45, 41, and 8 significantly different spots when AMI, UAP, and SAP were compared with the control group. On the basis of our proteomic data, plasma levels of two of them, alpha-1 microglobulin and vitamin D-binding protein, were determined. The data, however, failed to prove the proteins to be suitable markers or risk factors in the studied groups. The plasma level and isoform representation of apolipoprotein A1 were also estimated. Using 1D and 2D SDS-PAGE, together with western blotting, we observed extra high-molecular weight apolipoprotein A1 fractions presented only in the patient groups, indicating that the novel high-molecular weight isoforms of apolipoprotein A1 may be potential new markers or possible risk factors of cardiovascular disease. Conclusion The reported data show plasma proteome changes in patients with AMI, UAP, and SAP. We propose some apolipoprotein A1 fractions as a possible new disease-associated marker of cardiovascular disorders.

  11. Metabolism and Modification of Apolipoprotein B-Containing Lipoproteins Involved in Dyslipidemia and Atherosclerosis.

    Science.gov (United States)

    Morita, Shin-ya

    2016-01-01

    Increased levels of apolipoprotein B (apoB)-containing lipoproteins, such as low density lipoproteins (LDL) and chylomicron remnants, are associated with the development of atherosclerosis. Chylomicrons containing apoB-48 are secreted from the intestine during the postprandial state, whereas very low density lipoproteins (VLDL) containing apoB-100 are constitutively formed in the liver. Chylomicron remnants and VLDL remnants are produced by the lipoprotein lipase-mediated lipolysis of triglycerides, which is activated by apolipoprotein C-II bound on the particle surfaces. The hepatic uptake of these remnants is facilitated by apolipoprotein E (apoE), but is inhibited by apolipoproteins C-I, C-II and C-III. In the plasma, VLDL remnants are further converted into LDL by the hydrolysis of triglycerides. ApoB-100 is responsible for the hepatic uptake of LDL. LDL receptor, LDL receptor-related protein and heparan sulfate proteoglycans are involved in the hepatic clearance of lipoproteins containing apoB-100 and/or apoE. The subendothelial retention and modification of apoB-containing lipoproteins are crucial events in the initiation of atherosclerosis. In the subendothelium, the uptake of modified lipoproteins by macrophages leads to the formation of foam cells storing excess amounts of cholesteryl esters and subsequently to apoptosis. This review describes the current knowledge about the metabolism and modification of apoB-containing lipoproteins involved in dyslipidemia and atherogenesis. In particular, I focus on the effects of apolipoproteins, lipid composition and particle size on lipoprotein metabolism and on the roles of cholesterol, sphingomyelinase and apoB denaturation in macrophage foam cell formation and apoptosis. A detailed understanding of these mechanisms will help to develop new therapeutic strategies. PMID:26725424

  12. Biophysical analysis of apolipoprotein E3 variants linked with development of type III hyperlipoproteinemia.

    Directory of Open Access Journals (Sweden)

    Dimitra Georgiadou

    Full Text Available BACKGROUND: Apolipoprotein E (apoE is a major protein of the lipoprotein transport system that plays important roles in lipid homeostasis and protection from atherosclerosis. ApoE is characterized by structural plasticity and thermodynamic instability and can undergo significant structural rearrangements as part of its biological function. Mutations in the 136-150 region of the N-terminal domain of apoE, reduce its low density lipoprotein (LDL receptor binding capacity and have been linked with lipoprotein disorders, such as type III hyperlipoproteinemia (HLP in humans. However, the LDL-receptor binding defects for these apoE variants do not correlate well with the severity of dyslipidemia, indicating that these variants may carry additional properties that contribute to their pathogenic potential. METHODOLOGY/PRINCIPAL FINDINGS: In this study we examined whether three type III HLP predisposing apoE3 variants, namely R136S, R145C and K146E affect the biophysical properties of the protein. Circular dichroism (CD spectroscopy revealed that these mutations do not significantly alter the secondary structure of the protein. Thermal and chemical unfolding analysis revealed small thermodynamic alterations in each variant compared to wild-type apoE3, as well as effects in the reversibility of the unfolding transition. All variants were able to remodel multillamelar 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC vesicles, but R136S and R145C had reduced kinetics. Dynamic light scattering analysis indicated that the variant R136S exists in a higher-order oligomerization state in solution. Finally, 1-anilinonaphthalene-8-sulfonic acid (ANS binding suggested that the variant R145C exposes a larger amount of hydrophobic surface to the solvent. CONCLUSIONS/SIGNIFICANCE: Overall, our findings suggest that single amino acid changes in the functionally important region 136-150 of apoE3 can affect the molecule's stability and conformation in solution and may

  13. Sex differences in apolipoprotein A1 and nevirapine-induced toxicity

    Directory of Open Access Journals (Sweden)

    Aline Marinho

    2014-11-01

    Full Text Available Nevirapine (NVP is associated with severe liver and skin toxicity through sulfotransferase (SULT bioactivation of the phase I metabolite 12-hydroxy-NVP [1–3]. The female sex, a well-known risk factor for NVP-induced toxicity, is associated with higher SULT expression (4 and lower plasma levels of 12-hydroxy-NVP [3]. Interestingly, apolipoprotein A1 (ApoA1 increases SULT2B1 activity and ApoA1 synthesis is increased by NVP [5, 6]. Herein, we explore the effect of ApoA1 levels on NVP metabolism and liver function. The study protocol was firstly approved by the hospitals’ Ethics Committees. All included individuals were HIV-infected patients treated with NVP for at least one month. The plasma concentrations of NVP and its phase I metabolites were quantified by HPLC [7]. ApoA1 levels were assessed by an immunoturbidimetric assay. Forty-nine HIV-infected patients on NVP were included (53% men, 59% Caucasian. NVP plasma levels were correlated with HDL-cholesterol (Spearman r=0.2631; p=0.0441 and ApoA1 (Spearman r=0.3907; p=0.0115. Women had higher ApoA1 levels than men (Student's t Test; p=0.0051. In both sexes, 12-hydroxy-NVP levels were negatively correlated with ApoA1 (male: Spearman r=−0.3810; p=0.0499 female: Spearman r=−0.5944; p=0.0415. In men, ApoA1 was positively correlated with aspartate aminotransferase (AST, Spearman r=0.5507; p=0.0413, while in women ApoA1 was associated (Spearman r=0.6408; p=0.0056 with alanine aminotransferase (ALT. These results show sex differences in NVP-induced ApoA1 synthesis. The higher ApoA1 levels in women might stabilize SULT2B1 [6]. This would explain the lower levels of 12-hydroxy-NVP [3] and the higher hepatotoxicity found in women, due to increased sulfonation of this metabolite. These data support a role for ApoA1 in the sex dimorphic mechanism leading to NVP-induced toxicity.

  14. Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Lundegaard, Christiane; Tybjærg-Hansen, Anne; Grande, Peer;

    2010-01-01

    Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD).......Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD)....

  15. Overexpression of LolCDE Allows Deletion of the Escherichia coli Gene Encoding Apolipoprotein N-Acyltransferase ▿

    OpenAIRE

    Narita, Shin-ichiro; Tokuda, Hajime

    2011-01-01

    Bacterial lipoproteins represent a subset of membrane-associated proteins that are covalently modified with lipids at the N-terminal cysteine. The final step of lipoprotein modification, N-acylation of apolipoproteins, is mediated by apolipoprotein N-acyltransferase (Lnt). Examinations with reconstituted proteoliposomes and a conditional mutant previously indicated that N-acylation of lipoproteins is required for their efficient release from the inner membrane catalyzed by LolA and LolCDE, th...

  16. Apolipoprotein E ε4 allele and malondialdehyde level are independent risk factors for Alzheimer’s disease

    OpenAIRE

    López-Riquelme, Natividad; Alom-Poveda, Jordi; Viciano-Morote, Nuria; Llinares-Ibor, Isabel; Tormo-Díaz, Consuelo

    2016-01-01

    Background: The ε4 allele of Apolipoprotein E is involved in lipid metabolism. Oxidative stress produces an increase in lipid peroxidation that has been implicated in the pathogenic cascade in Alzheimer’s disease. This study estimated the effect of the ε4 allele, malondialdehyde and lipid levels on the risk for Alzheimer’s disease. Methods: A total of 41 control subjects and 73 patients with Alzheimer’s disease were recruited. The Apolipoprotein E genotype was determined by amplification of e...

  17. Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil

    OpenAIRE

    Sumeet S Mitter; Oriá, Reinaldo B.; Kvalsund, Michelle P.; Paula Pamplona; Emanuella Silva Joventino; Rosa M. S. Mota; Davi C Gonçalves; Patrick, Peter D.; Guerrant, Richard L.; Lima, Aldo A. M.

    2012-01-01

    OBJECTIVE: Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, thereby improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children. METHODS: A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ) received 200,000 IU of retinol (every four months), zinc (40 mg twice we...

  18. Structural and electronic properties of GaN nanowires with embedded In{sub x}Ga{sub 1−x}N nanodisks

    Energy Technology Data Exchange (ETDEWEB)

    Kioseoglou, J., E-mail: sifisl@auth.gr; Pavloudis, Th.; Kehagias, Th.; Komninou, Ph.; Karakostas, Th. [Department of Physics, Aristotle University of Thessaloniki, GR-54124 Thessaloniki (Greece); Latham, C. D.; Rayson, M. J. [Department of Chemistry, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom); Briddon, P. R. [School of Electrical and Electronic Engineering, Newcastle University, Newcastle upon Tyne NE1 7RU (United Kingdom); Eickhoff, M. [Institute of Experimental Physics I, Justus-Liebig-University Giessen, D-35392 Giessen (Germany)

    2015-07-21

    In the present study, the effects of various types of strain and indium concentration on the total energy and optoelectronic properties of GaN nanowires (NWs) with embedded In{sub x}Ga{sub 1−x}N nanodisks (NDs) are examined. In particular, the bi-axial, hydrostatic, and uniaxial strain states of the embedded In{sub x}Ga{sub 1−x}N NDs are investigated for multiple In concentrations. Density functional theory is employed to calculate the band structure of the NWs. The theoretical analysis finds that the supercell-size-dependent characteristics calculated for our 972-atom NW models are very close to the infinite supercell-size limit. It is established that the embedded In{sub x}Ga{sub 1−x}N NDs do not induce deep states in the band gap of the NWs. A bowing parameter of 1.82 eV is derived from our analysis in the quadratic Vegard's formula for the band gaps at the various In concentrations of the investigated In{sub x}Ga{sub 1−x}N NDs in GaN NW structures. It is concluded that up to ∼10% of In, the hydrostatic strain state is competitive with the bi-axial due to the radial absorption of the strain on the surfaces. Above this value, the dominant strain state is the bi-axial one. Thus, hydrostatic and bi-axial strain components coexist in the embedded NDs, and they are of different physical origin. The bi-axial strain comes from growth on lattice mismatched substrates, while the hydrostatic strain originates from the lateral relaxation of the surfaces.

  19. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Bentzen, Joan; Poulsen, Pernille; Vaag, Allan;

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco...... on the insulin-to-glucose ratio (p = 0.04), and E4154K (EcoRI RFLP) influenced HOMAbeta (p = 0.04). Significant interactions were observed between genotype in T71I (ApaLI RFLP), A591V (AluI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI RFLP) and glucose tolerance on lipid-related parameters (0.03 < p...

  20. Endothelial surface layer degradation by chronic hyaluronidase infusion induces proteinuria in apolipoprotein e-deficient mice

    OpenAIRE

    Meuwese, Marijn C.; Broekhuizen, Lysette N.; Mayella Kuikhoven; Sylvia Heeneman; Esther Lutgens; Marion J J Gijbels; Max Nieuwdorp; Peutz, Carine J; Stroes, Erik S.G.; Hans Vink; van den Berg, Bernard M.

    2010-01-01

    OBJECTIVE: Functional studies show that disruption of endothelial surface layer (ESL) is accompanied by enhanced sensitivity of the vasculature towards atherogenic stimuli. However, relevance of ESL disruption as causal mechanism for vascular dysfunction remains to be demonstrated. We examined if loss of ESL through enzymatic degradation would affect vascular barrier properties in an atherogenic model. METHODS: Eight week old male apolipoprotein E deficient mice on Western-type diet for 10 we...

  1. Expression analysis of apolipoprotein E and its associated genes in gastric cancer

    OpenAIRE

    Shi, Xiumin; Xu, Jianting; Wang, Jihan; CUI, MEIZI; Gao, Yushun; Niu, Haitao; Jin, Haofan

    2015-01-01

    Gastric cancer is a common type of cancer worldwide, and has a poor prognosis, in part due to the low rates of early diagnosis and the limited treatment methods available. Apolipoprotein E (ApoE) is involved in exogenous cholesterol transport and may be important in enabling tumor cells to fulfill their high cholesterol requirements. A number of reports have indicated that ApoE affects the development and prognosis of gastric cancer. Therefore, the aim of the present study was to investigate ...

  2. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway

    OpenAIRE

    Lawn, Richard M.; Wade, David P.; Garvin, Michael R.; Wang, Xingbo; Schwartz, Karen; Porter, J. Gordon; Seilhamer, Jeffrey J.; Ashley M Vaughan; Oram, John F.

    1999-01-01

    The ABC1 transporter was identified as the defect in Tangier disease by a combined strategy of gene expression microarray analysis, genetic mapping, and biochemical studies. Patients with Tangier disease have a defect in cellular cholesterol removal, which results in near zero plasma levels of HDL and in massive tissue deposition of cholesteryl esters. Blocking the expression or activity of ABC1 reduces apolipoprotein-mediated lipid efflux from cultured cells, and increasing expression of ABC...

  3. Apolipoprotein E gene polymorphism influences aggressive behavior in prostate cancer cells by deregulating cholesterol homeostasis

    OpenAIRE

    IFERE, GODWIN O.; Desmond, Renee; Demark-Wahnefried, Wendy; Nagy, Tim R.

    2013-01-01

    High circulating cholesterol and its deregulated homeostasis may facilitate prostate cancer progression. Genetic polymorphism in Apolipoprotein (Apo) E, a key cholesterol regulatory protein may effect changes in systemic cholesterol levels. In this investigation, we determined whether variants of the Apo E gene can trigger defective intracellular cholesterol efflux, which could promote aggressive prostate cancer. ApoE genotypes of weakly (non-aggressive), moderate and highly tumorigenic (aggr...

  4. Apolipoprotein A-I and its mimetics for the treatment of atherosclerosis

    OpenAIRE

    Smith, Jonathan D.

    2010-01-01

    Although statin treatment leads consistently to a reduction in major adverse coronary events and death in clinical trials, approximately 60 to 70% residual risk of these outcomes still remains. One frontier of investigational drug research is treatment to increase HDL, the ‘good cholesterol’ that is associated with a reduced risk of coronary artery disease. HDL and its major protein apolipoprotein A-I (apoAI) are protective against atherosclerosis through several mechanisms, including the abi...

  5. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  6. Mutation in apolipoprotein B associated with hypobetalipoproteinemia despite decreased binding to the low density lipoprotein receptor

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan Skov; Nilausen, Karin Skov; Meinertz, Hans; Tybjaerg-Hansen, Anne

    2005-01-01

    Mutations in apolipoprotein B (APOB) may reduce binding of low density lipoprotein (LDL) to the LDL receptor and cause hypercholesterolemia. We showed that heterozygotes for a new mutation in APOB have hypobetalipoproteinemia, despite a reduced binding of LDL to the LDL receptor. APOB R3480P hete...... in vitro studies with both human in vivo and population-based studies, as in vitro studies often have focused on very limited aspects of complex mechanisms taken out of their natural context....

  7. Apolipoprotein E Polymorphism and Colorectal Neoplasm: Results from a Meta-Analysis

    OpenAIRE

    Tian, Yun; Wang, Jirong; Ye, Ying; Sun, Liqun; Fan, Yingrui; Wang, Li; Juan LI; Wang, Zhaoxia; Wang, Keming

    2014-01-01

    To investigate the relationship of Apolipoprotein E (APOE) gene polymorphism to colorectal neoplasia (CRN), we performed a systematic review and meta-analysis. Eligible studies were identified through a systematic literature review from PubMed, EMBASE, and the Science Citation Index up to February 2014. A combined analysis was performed, followed by a subgroup analyses stratified by the study design. We used data collected from 8 prospective studies involving respectively a total of 9243 part...

  8. Perbedaan Kadar Apolipoprotein-B pada Diabetes Melitus Tipe 2 Terkontrol dan Tidak terkontrol

    OpenAIRE

    Sembiring, Budi Darmanta

    2015-01-01

    Background : Apolipoprotein-B (apo-B) is the major protein component of atherogenic lipoproteins such as VLDL, IDL, LDL. Type 2 DM apo-B act a better indicator of the progression of coronary artery disease compared with other lipids and lipoproteins . Objective : To determine differences in levels of apo-B in patients with type 2 diabetes mellitus controlled and uncontrolled blood sugar levels then for further can estimate the magnitude of the risk of coronary heart disease (CHD) in patien...

  9. The Apolipoprotein E Gene and Taq1A Polymorphisms in Childhood Obesity

    OpenAIRE

    Ergun, Mehmet Ali; Karaoguz, Meral Yirmibes; Koc, Altug; Camurdan, Orhun; Bideci, Aysun; Yazici, A. Canan; Cinaz, Peyami

    2010-01-01

    Obesity is a multifactorial disease that is influenced by genetic and environmental factors. The apolipoprotein E (Apo E) polymorphism has been reported to influence some lipid profile abnormalities associated with obesity in childhood. In this study, the relationship between the Apo E gene and Taq1A polymorphisms with childhood obesity has been studied. Regarding the Apo E genotypes, e3/4 was the most frequent in both the patient and control groups. Further, there was a significance between ...

  10. Apolipoprotein M binds oxidized phospholipids and increases the antioxidant effect of HDL

    DEFF Research Database (Denmark)

    Elsøe, Sara; Ahnström, Josefin; Christoffersen, Christina;

    2012-01-01

    Oxidation of LDL plays a key role in the development of atherosclerosis. HDL may, in part, protect against atherosclerosis by inhibiting LDL oxidation. Overexpression of HDL-associated apolipoprotein M (apoM) protects mice against atherosclerosis through a not yet clarified mechanism. Being a lip...... lipocalin, apoM contains a binding pocket for small lipophilic molecules. Here, we report that apoM likely serves as an antioxidant in HDL by binding oxidized phospholipids, thus enhancing the antioxidant potential of HDL....

  11. Association of hepatic nuclear factor-4 in the apolipoprotein B promoter: a preliminary report

    OpenAIRE

    Nóvak E.M.; Dantas K.C.; Charbel C.E.; Bydlowski S.P.

    1998-01-01

    Previous studies have examined the arrangement of regulatory elements along the apolipoprotein B (apoB) promoter region (-3067 to +940) and a promoter fragment extending from nucleotides -150 to +124 has been demonstrated to be essential for transcriptional activation of the apoB gene in hepatic and intestinal cells. It has also been shown that transcriptional activation of apoB requires a synergistic interaction between hepatic nuclear factor-4 (HNF-4) and CCAAT/enhancer-binding protein a (C...

  12. Guanosine effect on cholesterol efflux and apolipoprotein E expression in astrocytes.

    Science.gov (United States)

    Ballerini, Patrizia; Ciccarelli, Renata; Di Iorio, Patrizia; Buccella, Silvana; D'Alimonte, Iolanda; Giuliani, Patricia; Masciulli, Arianna; Nargi, Eleonora; Beraudi, Alina; Rathbone, Michel P; Caciagli, Francesco

    2006-11-01

    The main source of cholesterol in the central nervous system (CNS) is represented by glial cells, mainly astrocytes, which also synthesise and secrete apolipoproteins, in particular apolipoprotein E (ApoE), the major apolipoprotein in the brain, thus generating cholesterol-rich high density lipoproteins (HDLs). This cholesterol trafficking, even though still poorly known, is considered to play a key role in different aspects of neuronal plasticity and in the stabilisation of synaptic transmission. Moreover, cell cholesterol depletion has recently been linked to a reduction in amyloid beta formation. Here we demonstrate that guanosine, which we previously reported to exert several neuroprotective effects, was able to increase cholesterol efflux from astrocytes and C6 rat glioma cells in the absence of exogenously added acceptors. In this effect the phosphoinositide 3 kinase/extracellular signal-regulated kinase 1/2 (PI3K/ERK1/2) pathway seems to play a pivotal role. Guanosine was also able to increase the expression of ApoE in astrocytes, whereas it did not modify the levels of ATP-binding cassette protein A1 (ABCA1), considered the main cholesterol transporter in the CNS. Given the emerging role of cholesterol balance in neuronal repair, these effects provide evidence for a role of guanosine as a potential pharmacological tool in the modulation of cholesterol homeostasis in the brain. PMID:18404467

  13. Altered plasma apolipoprotein modifications in patients with pancreatic cancer: protein characterization and multi-institutional validation.

    Directory of Open Access Journals (Sweden)

    Kazufumi Honda

    Full Text Available BACKGROUND: Among the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection. METHODS: We compared the plasma protein profiles of 112 pancreatic cancer patients with those of 103 sex- and age-matched healthy controls (Cohort 1 using a newly developed matrix-assisted laser desorption/ionization (oMALDI QqTOF (quadrupole time-of-flight mass spectrometry (MS system. RESULTS: We found that hemi-truncated apolipoprotein AII dimer (ApoAII-2; 17252 m/z, unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 m/z, and their summed value were significantly decreased in the pancreatic cancer patients [P = 1.36×10(-21, P = 4.35×10(-14, and P = 1.83×10(-24 (Mann-Whitney U-test; area-under-curve values of 0.877, 0.798, and 0.903, respectively]. The significance was further validated in a total of 1099 plasma/serum samples, consisting of 2 retrospective cohorts [Cohort 2 (n = 103 and Cohort 3 (n = 163] and a prospective cohort [Cohort 4 (n = 833] collected from 8 medical institutions in Japan and Germany. CONCLUSIONS: We have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.

  14. Apolipoproteins: Good Markers for Cardiovacular Risk in Patients with Chronic Kidney Disease and Dyslipidemia

    Directory of Open Access Journals (Sweden)

    Tudor Mirela - Nicoleta

    2014-09-01

    Full Text Available Background and aims. Dyslipidemia (DLP is a common complication of chronic kidney disease (CKD and may accelerate its progression. Circulating lipoproteins and their constituent proteins, apolipoproteins, are risk factors for CKD and cardiovascular diseases (CVD. The aim of the study was to determine whether there is a correlation between apolipoproteins and estimated glomerular filtration rate (eGFR or between apolipoproteins and anthropometrical and laboratory parameters or between evaluated cardiovascular risk (CV and dyslipidemia/CKD. Material and methods. We performed a study on 51 subjects from the Nephrology Department of Emergency Clinical County Hospital of Craiova, from November 2011 to July 2013. Results. We found statistically significant correlations between eGFR and Apo A1. Also we found a linear correlation between C-reactive protein (CRP and Apo B. When we evaluated the CV risk using CRP, we found statistically significant differences between the groups (CKD and DLP, only CKD, only DLP and control group, patients with CKD and DLP showing the highest levels of CRP. Conclusions. Elevated levels of Apo A1 are associated with a low rate of CKD. DLP and chronic inflammation play an important role in the progression of CKD. Patients with CKD and DLP had a high cardiovascular risk.

  15. Genetic variation of apolipoproteins, diet and other environmental interactions: an updated review

    Directory of Open Access Journals (Sweden)

    Mercedes Sotos-Prieto

    2013-08-01

    Full Text Available This paper summarizes the recent findings from studies investigating the potential environmental modulation of the genetic variation of apolipoprotein genes on metabolic traits. We reviewed nutrigenetic studies evaluating variations on apolipoproteins-related genes and its associated response to nutrients (mostly dietary fatty acids or any other dietary or environmental component. Most revised research studied single nucleotide polymorphism (SNP and specific nutrients through small intervention studies, and only few interactions have been replicated in large and independent populations (as in the case of -265T > C SNP in APOA2 gene. Although current knowledge shows that variations on apolipoprotein genes may contribute to the different response on metabolic traits due to dietary interventions, evidence is still scarce and results are inconsistent. Success in this area will require going beyond the limitations of current experimental designs and explore the hypotheses within large populations. Some of these limitations are being covered by the rapidly advance in high-throughput technologies and large scale-genome wide association studies.

  16. Amyloid-β colocalizes with apolipoprotein B in absorptive cells of the small intestine

    Directory of Open Access Journals (Sweden)

    Dhaliwal Satvinder S

    2009-10-01

    Full Text Available Abstract Background Amyloid-β is recognized as the major constituent of senile plaque found in subjects with Alzheimer's disease. However, there is increasing evidence that in a physiological context amyloid-β may serve as regulating apolipoprotein, primarily of the triglyceride enriched lipoproteins. To consider this hypothesis further, this study utilized an in vivo immunological approach to explore in lipogenic tissue whether amyloid-β colocalizes with nascent triglyceride-rich lipoproteins. Results In murine absorptive epithelial cells of the small intestine, amyloid-β had remarkable colocalization with chylomicrons (Manders overlap coefficient = 0.73 ± 0.03 (SEM, the latter identified as immunoreactive apolipoprotein B. A diet enriched in saturated fats doubled the abundance of both amyloid-β and apo B and increased the overlap coefficient of the two proteins (0.87 ± 0.02. However, there was no evidence that abundance of the two proteins was interdependent within the enterocytes (Pearson's Coefficient Conclusion The findings of this study are consistent with the possibility that amyloid-β is secreted by enterocytes as an apolipoprotein component of chylomicrons. However, secretion of amyloid-β appears to be independent of chylomicron biogenesis.

  17. Acute effects of moderate exercise on serum lipids, lipoproteins and apolipoproteins in sedentary young women.

    Science.gov (United States)

    Imamura, H; Katagiri, S; Uchid, K; Miyamoto, N; Nakano, H; Shirota, T

    2000-12-01

    1. The aim of the present study was to examine the effects of moderate exercise on serum lipids, lipoproteins and apolipoproteins in seven sedentary young women under controlled conditions. 2. The subjects exercised on separate days for 30 or 60 min at an intensity of 60% of maximal oxygen uptake on a cycle ergometer. Total cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-C), HDL2-C, HDL3-C, low-density lipoprotein-cholesterol, apolipoproteins A-I, A-II and B were measured in the serum at the end of the 60 min rest period before each exercise, immediately after the performance of each exercise and at 30 min and 1, 2 and 24 h after each exercise. 3. The results showed that there were no significant differences between the pre- and postexercise samples for any of the parameters tested. 4. The results of the present study suggest that a single bout of exercise designed to simulate a typical training workout has no noticeable effect on serum lipids, lipoproteins and apolipoproteins in normal sedentary young women who have normal lipid profiles, are in the follicular phase of their menstrual cycle and who consume a relatively low-fat diet. PMID:11117233

  18. Effects of red grape juice consumption on high density lipoprotein-cholesterol, apolipoprotein AI, apolipoprotein B and homocysteine in healthy human volunteers.

    Science.gov (United States)

    Khadem-Ansari, Mohammad H; Rasmi, Yousef; Ramezani, Fatemeh

    2010-01-01

    It has suggested that grape juice consumption has lipid- lowering effect and it is associated with a decreased risk of heart disease. We aimed to evaluate the effects of red grape juice (RGj) consumption on high density lipoprotein-cholesterol (HDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB) and homocysteine (Hcy) levels in healthy human volunteers. Twenty six healthy and nonsmoking males, aged between 25-60 years, who were under no medication asked to consume 150 ml of RGj twice per day for one month. Serum HDL-C, apoAI, apoB and plasma Hcy levels were measured before and after one month RGj consumption. HDL-C levels after RGj consumption were significantly higher than the corresponding levels before the RGj consumption (41.44 ± 4.50 and 44.37 ± 4.30 mg/dl; P0.05). Hcy levels were decreased after RGj consumption (7.70 ± 2.80 and 6.20 ± 2.30 µmol/l; P<0.001). The present study demonstrates that RGj consumption can significantly increase serum HDL-C levels and decrease Hcy levels. These findings may have important implications for the prevention of atherosclerosis in healthy individuals. PMID:21633724

  19. 17β-estradiol potentiates endothelium-dependent nitric oxide- and hyperpolarization-mediated relaxations in blood vessels of male but not female apolipoprotein-E deficient mice.

    Science.gov (United States)

    Kong, Billy W C; Vanhoutte, Paul M; Man, Ricky Y K; Leung, Susan W S

    2015-08-01

    The present study investigated the influence of gender on the changes underlying endothelial dysfunction in hyperlipidemia during aging. Isometric tension in rings (with endothelium) of the aortae and superior mesenteric arteries from apolipoprotein-E deficient mice was determined in wire myographs. Nitric oxide (NO)- and endothelium-dependent hyperpolarization (EDH)-mediated relaxations were smaller in the aortae and mesenteric arteries of 32weeks old males than eight weeks old males. In females, NO- and EDH-mediated relaxations were impaired only at 84weeks of age. The levels of reactive oxygen species were elevated in the blood vessels of 32weeks old males, but not females. Acute in vitro treatment with 17β-estradiol and apocynin improved NO- and EDH-mediated relaxations in 32weeks old males but not in 84weeks old males. Relaxations to SKA-31, activator of intermediate (IKCa) and small (SKCa) conductance calcium-activated potassium channels, were attenuated in the mesenteric arteries of 32weeks old males. Such impairment was restored by acute treatment with apocynin. These findings suggest that male hyperlipidemic mice develop endothelial dysfunction at an earlier age than females. This endothelial dysfunction is associated with impaired NO bioavailability and reduced IKCa and SKCa activity. Apocynin and 17β-estradiol restore the endothelial function only in younger male animals but not in older male or female animals. PMID:25869512

  20. Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

    Directory of Open Access Journals (Sweden)

    García-Arias Carlota

    2009-06-01

    Full Text Available Abstract Background Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. Methods Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases and 31 patients with severe hypertriglyceridaemia (controls were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. Results Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS. Conclusion Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood.

  1. Kan apolipoprotein-nivåer målt fra opptinte blodprøver etter 12-14 års nedfrysing brukes for epidemiologiske formål? En pilotanalyse av HUNT 2-data

    Directory of Open Access Journals (Sweden)

    Ingar Holme

    2011-03-01

    kan imidlertid først oppnås når slike opptinte prøver blir analysert.Can frozen and thawed blood samples stored for 12-14 years be used to measure levels of apolipoproteins? Analysis from HUNT 2 data.            English Summary: In Norway, large numbers of frozen blood samples from health surveys are stored in freezers at –70 to –80 ºC. An assumption has been that levels of lipoproteins (total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol (HDL-C and triglycerides (TG have been kept at constant levels during long-term storage. The stability of long-term storage of apolipoproteins is weakly documented. The Health Survey of Nord-Trøndelag in 1995-97 (HUNT 2 provides the possibility to analyse relationships between levels of lipoproteins and incident cardiovascular disease. A project group consisting of the present authors questioned whether use of apolipoproteins as risk markers may give at least as good predictive value as the traditional lipoproteins and whether the frozen samples in HUNT 2 can be used for this purpose. To investigate this issue a pilot study based on 300 thawed blood samples from HUNT 2 was performed. For these subjects lipoprotein levels measured at screening in 1995-97 were available as well as the same levels from the thawed samples including also apolipoprotein B (apoB and apolipoprotein A-1 (apoA-1. For special reasons these samples had only been frozen down to –40 ºC.

  2. Apolipoprotein A-II influences apolipoprotein E-linked cardiovascular disease risk in women with high levels of HDL cholesterol and C-reactive protein.

    Directory of Open Access Journals (Sweden)

    James P Corsetti

    Full Text Available BACKGROUND: In a previous report by our group, high levels of apolipoprotein E (apoE were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP in the setting of both low (designated as HR1 subjects and high (designated as HR2 subjects levels of high-density lipoprotein cholesterol (HDL-C. To assess whether apolipoprotein A-II (apoA-II plays a role in apoE-associated risk in the two female groups. METHODOLOGY/PRINCIPAL: Outcome event mapping, a graphical data exploratory tool; Cox proportional hazards multivariable regression; and curve-fitting modeling were used to examine apoA-II influence on apoE-associated risk focusing on HDL particles with apolipoprotein A-I (apoA-I without apoA-II (LpA-I and HDL particles with both apoA-I and apoA-II (LpA-I:A-II. Results of outcome mappings as a function of apoE levels and the ratio of apoA-II to apoA-I revealed within each of the two populations, a high-risk subgroup characterized in each situation by high levels of apoE and additionally: in HR1, by a low value of the apoA-II/apoA-I ratio; and in HR2, by a moderate value of the apoA-II/apoA-I ratio. Furthermore, derived estimates of LpA-I and LpA-I:A-II levels revealed for high-risk versus remaining subjects: in HR1, higher levels of LpA-I and lower levels of LpA-I:A-II; and in HR2 the reverse, lower levels of LpA-I and higher levels of LpA-I:A-II. Results of multivariable risk modeling as a function of LpA-I and LpA-I:A-II (dichotomized as highest quartile versus combined three lower quartiles revealed association of risk only for high levels of LpA-I:A-II in the HR2 subgroup (hazard ratio 5.31, 95% CI 1.12-25.17, p = 0.036. Furthermore, high LpA-I:A-II levels interacted with high apoE levels in establishing subgroup risk. CONCLUSIONS/SIGNIFICANCE: We conclude that apoA-II plays a significant role in apoE-associated risk of incident CVD in women with high levels of HDL-C and CRP.

  3. Polymorphism of apolipoprotein E gene and post-stroke vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Xinjing Lin; Changlin Hu; Yunlan Xie; Xin Zhang; Xiangping Liu; Ge Yan

    2006-01-01

    BACKGROUND: Studies have indicated that the more certain etiological factors of vascular dementia are the sites, size and number of cerebrovascular lesions, but there are arguments all the time in the relationship of genetic factors, especially apolipoprotein E gene, with the occurrence and development of vascular dementia. OBJECTIVE: To analyze the relationship between the polymorphism of apolipoprotein E gene and vascular dementia in stroke patients. DESIGN: A non-randomized grouped comparative observation at the same time. SETTING: The Laboratory of Neurology, the Second Affiliated Hospital of Chongqing University of Medical Sciences.PARTICIPANTS: Totally 121 inpatients with stroke were selected from the Department of Neurology, the Second Affiliated Hospital of Chongqing University of Medical Sciences from January 2000 to December 2001. All the patients were accorded with the diagnostic standards for cerebrovascular diseases set by the Second National Academic Meeting for Cerebrovascular Disease, and confirmed by cranial CT or MRI. According to with vascular dementia or not, they were divided into vascular dementia group (n =58) and non-vascular dementia group (n =63). In the vascular dementia group, there were 37 males and 21 females, the average age was (59±8) years. They were all in accordance with the standard of the third edition of Diagnostic and Statistical Manual of Mental Disorders (DMS-Ⅲ), without conscious disturbance and language disorder; hospitalized within 3 days after the attack of cerebrovascular disease. In the non-vascular dementia group, there were 37 males and 26 females, the average age was (59±9.5) years. They all had no intellectual disturbance within 3 months after the attack of cerebrovascular disease. All the subjects agreed to supply blood samples for the experiment. METHODS: ①Fasting venous blood (2 mL) was drawn from each patient in the morning to extract DNA. The frequencies of apolipoprotein E genotypes and alleles were

  4. Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.

    Directory of Open Access Journals (Sweden)

    Makoto Shimizu

    Full Text Available Quercetin is one of the most abundant polyphenolic flavonoids found in fruits and vegetables and has anti-oxidative and anti-obesity effects. Because the small intestine is a major absorptive organ of dietary nutrients, it is likely that highly concentrated food constituents, including polyphenols, are present in the small intestinal epithelial cells, suggesting that food factors may have a profound effect in this tissue. To identify novel targets of quercetin in the intestinal enterocytes, mRNA profiling using human intestinal epithelial Caco-2 cells was performed. We found that mRNA levels of some apolipoproteins, particularly apolipoprotein B (apoB, are downregulated in the presence of quercetin. On the exposure of Caco-2 cells to quercetin, both mRNA and protein levels of apoB were decreased. Promoter analysis of the human apoB revealed that quercetin response element is localized at the 5'-proximal promoter region, which contains a conserved CCAAT enhancer-binding protein (C/EBP-response element. We found that quercetin reduces the promoter activity of apoB, driven by the enforced expression of C/EBPβ. Quercetin had no effect on either mRNA or protein levels of C/EBPβ. In contrast, we found that quercetin inhibits the transcriptional activity of C/EBPβ but not its recruitment to the apoB promoter. On the exposure of Caco-2 cells to quercetin 3-O-glucuronide, which is in a cell-impermeable form, no notable change in apoB mRNA was observed, suggesting an intracellular action of quercetin. In vitro interaction experiments using quercetin-conjugated beads revealed that quercetin binds to C/EBPβ. Our results describe a novel regulatory mechanism of transcription of apolipoprotein genes by quercetin in the intestinal enterocytes.

  5. Immunolocalization of an Amino-Terminal Fragment of Apolipoprotein E in the Pick's Disease Brain

    OpenAIRE

    Rohn, Troy T.; Day, Ryan J; Catlin, Lindsey W; Brown, Raquel J.; Rajic, Alexander J.; Poon, Wayne W.

    2013-01-01

    Although the risk factor for apolipoprotein E (apoE) polymorphism in Alzheimer's disease (AD) has been well described, the role that apoE plays in other neurodegenerative diseases, including Pick's disease, is not well established. To examine a possible role of apoE in Pick's disease, an immunohistochemical analysis was performed utilizing a novel site-directed antibody that is specific for an amino-terminal fragment of apoE. Application of this antibody, termed the amino-terminal apoE cleava...

  6. Bioenergetic programming of macrophages by the apolipoprotein A-I mimetic peptide 4F

    OpenAIRE

    Datta, Geeta; Kramer, Philip A.; Johnson, Michelle S.; Sawada, Hirotaka; Smythies, Lesley E.; Crossman, David K.; Chacko, Balu; Ballinger, Scott W.; Westbrook, David G.; Mayakonda, Palgunachari; Anantharamaiah, G.M.; Darley-Usmar, Victor M.; White, C. Roger

    2015-01-01

    The apoA-I (apolipoprotein A-I) mimetic peptide 4F favours the differentiation of human monocytes to an alternatively activated M2 phenotype. The goal of the present study was to test whether the 4F-mediated differentiation of MDMs (monocyte-derived macrophages) requires the induction of an oxidative metabolic programme. 4F treatment induced several genes in MDMs that play an important role in lipid metabolism, including PPARγ (peroxisome-proliferator-activated receptor γ) and CD36. Addition ...

  7. Angiotensin II-Induced Hypertension in Apolipoprotein E-Deficient Rats

    OpenAIRE

    Gorman, Sydney N; Goergen, Craig J.; Blaize, A Nicole

    2015-01-01

    Abdominal aortic aneurysms (AAAs) are characterized by a weakened vessel wall and a diameter 50% greater than normal. AAA are usually asymptomatic until they are near rupturing, which can be fatal if not treated immediately. Apolipoprotein E-deficient (ApoE) mice are commonly used as a model to study aneurysm growth. Our lab has created a similar model using rats, which are more similar to humans. This study focuses on the analysis of blood pressures collected from ApoE rats for comparison wi...

  8. Abolished synthesis of cholic acid reduces atherosclerotic development in apolipoprotein E knockout mice[S

    OpenAIRE

    Slätis, Katharina; Gåfvels, Mats; Kannisto, Kristina; Ovchinnikova, Olga; Paulsson-Berne, Gabrielle; Parini, Paolo; Jiang, Zhao-Yan; Eggertsen, Gösta

    2010-01-01

    To investigate the effects of abolished cholic acid (CA) synthesis in the ApoE knockout model [apolipoprotein E (apoE) KO],a double-knockout (DKO) mouse model was created by crossbreeding Cyp8b1 knockout mice (Cyp8b1 KO), unable to synthesize the primary bile acid CA, with apoE KO mice. After 5 months of cholesterol feeding, the development of atherosclerotic plaques in the proximal aorta was 50% less in the DKO mice compared with the apoE KO mice. This effect was associated with reduced inte...

  9. Apolipoprotein E4 Domain Interaction Induces Endoplasmic Reticulum Stress and Impairs Astrocyte Function*

    OpenAIRE

    Zhong, Ning; Ramaswamy, Gayathri; Weisgraber, Karl H.

    2009-01-01

    Domain interaction, a structural property of apolipoprotein E4 (apoE4), is predicted to contribute to the association of apoE4 with Alzheimer disease. Arg-61 apoE mice, a gene-targeted mouse model specific for domain interaction, have lower brain apoE levels and synaptic, functional, and cognitive deficits. We hypothesized that domain interaction elicits an endoplasmic reticulum (ER) stress in astrocytes and an unfolded protein response that targets Arg-61 apoE for degradation. Primary Arg-61...

  10. Effect of Biliary Diversion on Rat Mesenteric Lymph Apolipoprotein-I and High Density Lipoprotein

    OpenAIRE

    Bearnot, H. Robert; Glickman, Robert M.; Weinberg, Lee; Green, Peter H.R.; Tall, Alan R.

    1982-01-01

    The effect of biliary diversion on intestinal apolipoprotein (apoA)-I and high density lipoprotein formation was studied in mesenteric lymph fistula rats. Bile diversion was produced by an exteriorized catheter that allowed interruption and reconstitution of the enterohepatic circulation. Bile diversion reduced lymph cholesterol output from 0.47±0.05 μmol/h to 0.17±0.03 μmol/h (P < 0.025), and lymph triglyceride output from 3.6±0.3μmol/h to 0.6±0.05 μmol/h (P < 0.025) after 24 h. This was due...

  11. Apolipoprotein E4 and a change in episodic memory functioning among normal aging Norwegian adults

    OpenAIRE

    2009-01-01

    The e4 allele of the apolipoprotein E (APOE) gene is a known risk factor for Alzheimer’s disease and may also affect cognitive performance in normal aging. The data presented in the current study represent the first two time points of an ongoing longitudinal study examining cognitive changes in genetically at-risk individuals with much emphasis on test of episodic recall as measured by the California Verbal Learning Test. A total of 110 of 139 people who participated in the first phase of the...

  12. The impact of plasma triglyceride and apolipoproteins concentrations on high-density lipoprotein subclasses distribution

    Directory of Open Access Journals (Sweden)

    Liu Yinghui

    2011-01-01

    Full Text Available Abstract Objective To investigate the effect of triglyceride (TG integrates with plasma major components of apolipoproteins in HDL subclasses distribution and further elicited the TG-apolipoproteins (apos interaction in the processes of high density lipoprotein (HDL mature metabolic and atherosclerosis related diseases. Methods Contents of plasma HDL subclasses were quantities by two-dimensional gel electrophoresis associated with immunodetection in 500 Chinese subjects. Results Contents of preβ1-HDL, HDL3a, and apoB-100 level along with apoB-100/A-I ratio were significantly increased, whereas there was a significant reduction in the contents of HDL2, apoA-I level as well as apoC-III/C-II ratio with increased TG concentration. Moreover, preβ1-HDL contents is elevated about 9 mg/L and HDL2b contents can be reduced 21 mg/L for 0.5 mmol/L increment in TG concentration. Moreover, with increase of apoA-I levels, HDL2b contents were marginally elevated in any TG concentration group. Furthermore, despite of in the apoB-100/A-I 1-HDL increased, and those of HDL2b decreased significantly for subjects in both high and very high TG levels compared to that in normal TG levels. Similarly, in the apoB-100/A-I ≥ 0.9 group, the distribution of HDL subclasses also showed abnormality for subjects with normal TG levels. Conclusions The particle size of HDL subclasses tend to small with TG levels increased which indicated that HDL maturation might be impeded and efficiency of reverse cholesterol transport(RCT might be weakened. These data suggest that TG levels were not only significantly associated with but liner with the contents of preβ1-HDL and HDL2b. They also raise the possibility that the TG levels effect on HDL maturation metabolism are subjected to plasma apolipoproteins and apolipoproteins ratios.

  13. Interactions of Apolipoprotein A-I with High-Density Lipoprotein Particles

    OpenAIRE

    Nguyen, David; Nickel, Margaret; Mizuguchi, Chiharu; Saito, Hiroyuki; Lund-Katz, Sissel; Phillips, Michael C.

    2013-01-01

    Although the partitioning of apolipoprotein A-I (apoA-I) molecules in plasma between high-density lipoprotein (HDL)-bound and -unbound states is an integral part of HDL metabolism, the factors that control binding of apoA-I to HDL particles are poorly understood. To address this gap in knowledge, we investigated how the properties of the apoA-I tertiary structure domains and surface characteristics of spherical HDL particles influence apoA-I binding. The abilities of 14C-labeled human and mou...

  14. Surface behavior of apolipoprotein A-I and its deletion mutants at model lipoprotein interfaces

    OpenAIRE

    Wang, Libo; Mei, Xiaohu; Atkinson, David; Small, Donald M.

    2014-01-01

    Apolipoprotein A-I (apoA-I) has a great conformational flexibility to exist in lipid-free, lipid-poor, and lipid-bound states during lipid metabolism. To address the lipid binding and the dynamic desorption behavior of apoA-I at lipoprotein surfaces, apoA-I, Δ(185-243)apoA-I, and Δ(1-59)(185-243)apoA-I were studied at triolein/water and phosphatidylcholine/triolein/water interfaces with special attention to surface pressure. All three proteins are surface active to both interfaces lowering th...

  15. The apolipoprotein A-I gene is actively expressed in the rapidly myelinating avian peripheral nerve

    OpenAIRE

    1989-01-01

    The expression of the apolipoprotein A-I (apo A-I) gene was investigated in the myelinating sciatic nerve. Hybridization analysis with an apo A-I cDNA probe obtained from a cDNA library of mRNA isolated from rapidly myelinating chick sciatic nerve indicated that apo A-I coding transcripts increase during development in the chick sciatic nerve in parallel with the increase of myelin lamellae. Substantial apo A-I-like immunoreactivity in chick sciatic nerve homogenates was detected by Western b...

  16. No severe bottleneck during human evolution: evidence from two apolipoprotein C-II deficiency alleles.

    OpenAIRE

    Xiong, W J; Li, W. H.; Posner, I; Yamamura, T.; Yamamoto, A.; Gotto, A M; Chan, L

    1991-01-01

    The DNA sequences of a Japanese and a Venezuelan apolipoprotein (apo) C-II deficiency allele, of a normal Japanese apo C-II gene, and of a chimpanzee apo C-II gene were amplified by PCR, and their nucleotide sequences were determined on multiple clones of the PCR products. The normal Japanese sequence is identical to--and the chimpanzee sequence differs by only three nucleotides from--a previously published normal Caucasian sequence. In contrast, the two human mutant sequences each differ fro...

  17. Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation

    OpenAIRE

    Borhani, David W.; Rogers, Danise P.; Engler, Jeffrey A.; Brouillette, Christie G

    1997-01-01

    The structure of truncated human apolipoprotein A-I (apo A-I), the major protein component of high density lipoprotein, has been determined at 4-Å resolution. The crystals comprise residues 44–243 (exon 4) of apo A-I, a fragment that binds to lipid similarly to intact apo A-I and that retains the lipid-bound conformation even in the absence of lipid. The molecule consists almost entirely of a pseudo-continuous, amphipathic α-helix that is punctuated by kinks at regularly spaced proline residu...

  18. Human apolipoprotein C-II: complete nucleic acid sequence of preapolipoprotein C-II.

    OpenAIRE

    Fojo, S S; Law, S W; Brewer, H B

    1984-01-01

    Apolipoprotein (apo) C-II is a cofactor for lipoprotein lipase, the enzyme that catalyzes the hydrolysis of triglycerides on plasma triglyceride-rich lipoproteins. The complete coding sequence of apoC-II mRNA has been determined from an apoC-II clone isolated from a human liver cDNA library. A 17-base-long synthetic oligonucleotide based on amino acid residues 5-10 of apoC-II was utilized as a hybridization probe to select recombinant plasmids containing the apoC-II sequence. Two thousand fou...

  19. Erythrocyte-bound apolipoprotein B in relation to atherosclerosis, serum lipids and ABO blood group.

    Directory of Open Access Journals (Sweden)

    Boudewijn Klop

    Full Text Available INTRODUCTION: Erythrocytes carry apolipoprotein B on their membrane, but the determining factors of erythrocyte-bound apolipoprotein B (ery-apoB are unknown. We aimed to explore the determinants of ery-apoB to gain more insight into potential mechanisms. METHODS: Subjects with and without CVD were included (N = 398. Ery-apoB was measured on fresh whole blood samples using flow cytometry. Subjects with ery-apoB levels ≤ 0.20 a.u. were considered deficient. Carotid intima media thickness (CIMT was determined as a measure of (subclinical atherosclerosis. RESULTS: Mean ery-apoB value was 23.2% lower in subjects with increased CIMT (0.80 ± 0.09 mm, N = 140 compared to subjects with a normal CIMT (0.57 ± 0.08 mm, N = 258 (P = 0.007, adjusted P<0.001. CIMT and ery-apoB were inversely correlated (Spearman's r: -0.116, P = 0.021. A total of 55 subjects (13.6% were considered ery-apoB deficient, which was associated with a medical history of CVD (OR: 1.86, 95% CI 1.04-3.33; adjusted OR: 1.55; 95% CI 0.85-2.82. Discontinuation of statins in 54 subjects did not influence ery-apoB values despite a 58.4% increase in serum apolipoprotein B. Subjects with blood group O had significantly higher ery-apoB values (1.56 ± 0.94 a.u. when compared to subjects with blood group A (0.89 ± 1.15 a.u, blood group B (0.73 ± 0.1.12 a.u. or blood group AB (0.69 ± 0.69 a.u. (P-ANOVA = 0.002. CONCLUSION: Absence or very low values of ery-apoB are associated with clinical and subclinical atherosclerosis. While serum apolipoprotein B is not associated with ery-apoB, the ABO blood group seems to be a significant determinant.

  20. Inhibition of Endoplasmic Reticulum Stress and Atherosclerosis by 2-Aminopurine in Apolipoprotein E-Deficient Mice

    OpenAIRE

    Emmanuel Okoro; Zhong Mao Guo; Dong Fang Wu; Dezhi Yang; Lichun Zhou; Hong Yang

    2013-01-01

    We previously reported that the apolipoprotein (apo) B48-carrying lipoproteins obtained from apoE knockout (apoE −/− ) mice, so called E−/B48 lipoproteins, transformed mouse macrophages into foam cells and enhanced the phosphorylation of eukaryotic translation initiation factor 2 α (eIF-2 α ). Furthermore, the eIF-2 α phosphorylation inhibitor, 2-aminopurine (2-AP), attenuated E−/B48 lipoprotein-induced foam cell formation. The present report studied the effect of 2-AP on atherosclerosis in a...

  1. Apolipoprotein E gene and age-related macular degeneration in a Chinese population

    OpenAIRE

    Sun, Erdan; Lim, Apiradee; Liu, Xipu; Snellingen, Torkel; Wang, Ningli; Liu, Ningpu

    2011-01-01

    Purpose To examine the association between apolipoprotein E (APOE) polymorphisms and age-related macular degeneration (AMD) in a Chinese population. Methods The study consisted of 712 subjects, including 201 controls, 363 cases with early AMD, and 148 cases with exudative AMD. Genomic DNA was extracted from venous blood leukocytes. Common allelic variants of APOE (ε2, ε3, and ε4) were analyzed by PCR and direct sequencing. Results APOE ε3ε3 was the most frequent genotype, with a frequency of ...

  2. Apolipoprotein E genotypes do not influence the age of onset in Huntington's disease

    OpenAIRE

    Saft, C.; Andrich, J; Brune, N; Gencik, M; Kraus, P; Przuntek, H; Epplen, J

    2004-01-01

    Objective: The ε4 allele of the apolipoprotein E (ApoE) gene has been defined as a critical factor for early onset neurodegeneration in Pick's, Parkinson's, and Alzheimer's disease. Unexpectedly, the ε4 allele appeared to delay the age of onset in Huntington's disease (HD) patients. Furthermore, sex specific effects were reported on earlier age of onset due to the ApoE ε2ε3 genotype in males with HD. The age of onset of HD is known to be negatively correlated with increasing lengths of pathog...

  3. Apolipoprotein E allele-dependent pathogenesis: A model for age-related retinal degeneration

    OpenAIRE

    Malek, G; Johnson, L V; Mace, B E; Saloupis, P.; Schmechel, D E; Rickman, D. W.; Toth, C. A.; Sullivan, P. M.; Rickman, C. Bowes

    2005-01-01

    Age-related macular degeneration (AMD) is a late-onset, multifactorial, neurodegenerative disease of the retina and the leading cause of irreversible vision loss in the elderly in the Western world. We describe here a murine model that combines three known AMD risk factors: advanced age, high fat cholesterol-rich (HF-C) diet, and apolipoprotein E (apoE) genotype. Eyes of aged, targeted replacement mice expressing human apoE2, apoE3, or apoE4 and maintained on a HF-C diet show apoE isoform-dep...

  4. The allelic modulation of apolipoprotein E expression by oestrogen: potential relevance for Alzheimer's disease

    OpenAIRE

    Lambert, J; Coyle, N; Lendon, C

    2004-01-01

    Background: The ε4 allele of the apolipoprotein E (APOE) gene is a major genetic risk factor for Alzheimer's disease but appears to be associated with greater risk in women than in men. Some studies suggest that the level of APOE may of its own modulate the risk for Alzheimer's disease. Sex differences and an apparent benefit of oestrogen therapy suggest a role for oestrogen. APOE expression is influenced by oestrogen and oestrogen therapy may not benefit women bearing an APOE ε4 allele. Thes...

  5. Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil

    Directory of Open Access Journals (Sweden)

    Sumeet S Mitter

    2012-01-01

    Full Text Available OBJECTIVE: Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children. METHODS: A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ received 200,000 IU of retinol (every four months, zinc (40 mg twice weekly, or both for one year, with half of each group receiving glutamine supplementation for 10 days. Height-for-age z-scores, weight-for-age z-scores, weight-forheight z-scores, and lactulose:mannitol ratios were assessed during the initial four months of treatment. An average of four years (range 1.4-6.6 later, the children underwent cognitive testing to evaluate non-verbal intelligence, coding, verbal fluency, verbal learning, and delayed verbal learning. Apolipoprotein E4 carriage was determined by PCR analysis for 144 children. RESULTS: Thirty-seven children were apolipoprotein E4(+, with an allele frequency of 13.9%. Significant associations were found for vitamin A and glutamine with intestinal barrier function. Apolipoprotein E4(+ children receiving glutamine presented significant positive Pearson correlations between the change in height-for-age z-scores over four months and delayed verbal learning, along with correlated changes over the same period in weight-for-age z-scores and weight-for-height z-scores associated with non-verbal intelligence quotients. There was a significant correlation between vitamin A supplementation of apolipoprotein E4(+ children and improved delta lactulose/mannitol. Apolipoprotein E4(- children, regardless of intervention, exhibited negative Pearson correlations between the change in lactulose-to-mannitol ratio over four months and verbal learning and non-verbal intelligence. CONCLUSIONS: During development, apolipoprotein E4 may

  6. Plasma Apolipoprotein-M (ApoM Response to a Circuit Resistance Training Program

    Directory of Open Access Journals (Sweden)

    Abbass Ghanbari-Niaki

    2013-12-01

    Full Text Available Apolipoprotein M (Apo-M is a human novel protein of apolipoprotein classes and highly expressed in liver and kidney tissues. ApoM is mainly associated with high-density lipoprotein (HDL, and act as a chaperone for sphingosine-1-phosphate (S1P, promotes mobilization of cellular cholesterol, formation of larger-size of pre β-HDL, and a new biomarker in sepsis. The level of apoM in plasma/serum is affected by several factors such as pregnancy, hyperglycemia, plasma leptin concentration, obesity, diabetes, insulin concentration and physical exercise. It has been shown that the level of plasma ApoM was significantly lower in strenuous exercise group when compared with the non-exercise group. In the present study a reduction was observed after the 4 weeks of circuit resistance training program. This reduction might be due to a decrease in ApoM expression in liver and kidney or an increase in ApoM clearance, degradation and excretion in urine.

  7. Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding

    International Nuclear Information System (INIS)

    Previous in vivo turnover studies suggested that retarded clearance of low density lipoproteins (LDL) from the plasma of some hypercholesterolemic patients is due to LDL with defective receptor binding. The present study examined this postulate directly by receptor binding experiments. The LDL from a hypercholesterolemic patient (G.R.) displayed a reduced ability to bind to the LDL receptors on normal human fibroblasts. The G.R. LDL possessed 32% of normal receptor binding activity. Likewise, the G.R. LDL were much less effective than normal LDL in competing with 125I-labeled normal LDL for cellular uptake and degradation and in stimulating intracellular cholesteryl ester synthesis. The defect in LDL binding appears to be due to a genetic abnormality of apolipoprotein B-100: two brothers of the proband possess LDL defective in receptor binding, whereas a third brother and the proband's son have normally binding LDL. Further, the defect in receptor binding does not appear to be associated wit an abnormal lipid composition or structure of the LDL. Normal and abnormal LDL subpopulations were partially separated from plasma of two subjects by density-gradient ultracentrifugation, a finding consistent with the presence of a normal and a mutant allele. The affected family members appear to be heterozygous for this disorder, which has been designated familial defective apolipoprotein B-100. These studies indicate that the defective receptor binding results in inefficient clearance of LDL and the hypercholesterolemia observed in these patients

  8. Rapid radioimmunoassay of human apolipoproteins C-II and C-III

    Energy Technology Data Exchange (ETDEWEB)

    Gustafson, S.; Oestlund-Lindqvist, A.M.; Vessby, B. (Uppsala Univ. (Sweden))

    1984-06-01

    Apolipoprotein (apo) C-II is an activator of lipoprotein lipase, while apo C-III has the ability to inhibit apo C-II activated lipolysis. In order to study further the relationship between lipoprotein lipase mediated hydrolysis and the serum concentrations of apo C-II and apo C-III radioimmunoassays for these apolipoproteins have been developed. Formalin-treated Staphylococcus aureus Cowan I was used for immunoprecipitation and were shown to give rapid uptake of immune complexes that could easily be harvested by centrifugation. The assays were shown to be sensitive (10 ..mu..g/1), specific, precise (inter- and intra-assay coefficients of variation below 10%), rapid (completed in less than 6 h) and simple to perform. Delipidation of serum and lipoproteins had no effect on the results, indicating that the immunologically active sites of apo C-II and apo C-III are exposed to the aqueous environment under assay conditions. Serum apo C-II and apo C-III levels of normolipidaemic subjects were approximately 25 mg/1 and 110 mg/1, respectively. Highly significant positive correlations were found between VLDL apo C-II and VLDL apo C-III, respectively, and VLDL triglycerides, VLDL cholesterol and total serum TG. There was also a highly significant correlation between the HDL cholesterol concentration and the HDL apo C-III concentration.

  9. The apolipoprotein A-I mimetic peptide, ETC-642, reduces chronic vascular inflammation in the rabbit

    Science.gov (United States)

    2011-01-01

    Background High-density lipoproteins (HDL) and their main apolipoprotein, apoA-I, exhibit anti-inflammatory properties. The development of peptides that mimic HDL apolipoproteins offers a promising strategy to reduce inflammatory disease. This study aimed to compare the anti-inflammatory effects of ETC-642, an apoA-I mimetic peptide, with that of discoidal reconstituted HDL (rHDL), consisting of full-length apoA-I complexed with phosphatidylcholine, in rabbits with chronic vascular inflammation. Results New Zealand White rabbits (n = 10/group) were placed on chow supplemented with 0.2% (w/w) cholesterol for 6-weeks. The animals received two infusions of saline, rHDL (8 mg/kg apoA-I) or ETC-642 (30 mg/kg peptide) on the third and fifth days of the final week. The infusions of rHDL and ETC-642 were able to significantly reduce cholesterol-induced expression of intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the thoracic aorta (p ETC-642 treated rabbits were more effective at inhibiting the TNF-α-induced increase in ICAM-1, VCAM-1 and p65 than HDL isolated from saline treated rabbits (p ETC-642 causes anti-inflammatory effects that are comparable to rHDL in an animal model of chronic vascular inflammation and highlights that apoA-I mimetic peptides present a viable strategy for the treatment of inflammatory disease. PMID:22128776

  10. Association of apolipoprotein E polymorphism in late-onset Alzheimer's disease and vascular dementia in Brazilians

    Directory of Open Access Journals (Sweden)

    D.R.S. Souza

    2003-07-01

    Full Text Available The genetic basis for dementias is complex. A common polymorphism in the apolipoprotein E (APOE gene is considered to be the major risk factor in families with sporadic and late-onset Alzheimer's disease as well as in the general population. The distribution of alleles and genotypes of the APOE gene in late-onset Alzheimer's disease (N = 68, other late-life dementias (N = 39, and in cognitively normal controls (N = 58 was determined, as also was the risk for Alzheimer's disease associated with the epsilon4 allele. Peripheral blood samples were obtained from a total of 165 individuals living in Brazil aged 65-82 years. Genomic DNA was amplified by the polymerase chain reaction and the products were digested with HhaI restriction enzyme. APOE epsilon2 frequency was considerably lower in the Alzheimer's disease group (1%, and the epsilon3 allele and epsilon3/epsilon3 genotype frequencies were higher in the controls (84 and 72%, respectively as were the epsilon4 allele and epsilon3/epsilon4 genotype frequencies in Alzheimer's disease (25 and 41%, respectively. The higher frequency of the epsilon4 allele in Alzheimer's disease confirmed its role as a risk factor, while epsilon2 provided a weak protection against development of the disease. However, in view of the unexpectedly low frequency of the epsilon4 allele, additional analyses in a more varied Brazilian sample are needed to clarify the real contribution of apolipoprotein E to the development of Alzheimer's disease in this population.

  11. The concentration of apolipoprotein A-I decreases during experimentally induced acute-phase processes in pigs

    DEFF Research Database (Denmark)

    Carpintero, R.; Pineiro, M.; Andres, M.;

    2005-01-01

    In this work, apolipoprotein A-I (ApoA-I) was purified from pig sera. The responses of this protein after sterile inflammation and in animals infected with Actinobacillus pleuropneumoniae or Streptococcus suis were investigated. Decreases in the concentrations of ApoA-I, two to five times lower...

  12. 9-CIS-RETINOIC ACID REPRESSES ESTROGEN-INDUCED EXPRESSION OF THE VERY-LOW-DENSITY APOLIPOPROTEIN-II GENE

    NARCIS (Netherlands)

    SCHIPPERS, IJ; KLOPPENBURG, M; SNIPPE, L; AB, G

    1994-01-01

    The chicken very low density apolipoprotein II (apoVLDLII) gene is estrogen-inducible and specifically expressed in liver. We examined the possible involvement of the retinoid X receptor (RXR) and its ligand 9-cis-retinoic acid (9-cis-RA) in the activation of the apoVLDLII promoter. We first concent

  13. Apolipoprotein E genotype status affects habitual human blood mononuclear cell gene expression and its response to fish oil intervention

    NARCIS (Netherlands)

    Matualatupauw, J.C.; Radonjic, M.; Nieuwerth-van de Rest, O.; Groot, de C.P.G.M.; Geleijnse, J.M.; Müller, M.R.; Afman, L.A.

    2016-01-01

    Scope
    People who carry the apolipoprotein E4 (APOE4) single nucleotide polymorphism have an increased risk of cardiovascular disease (CVD). Fish-oil supplementation may help in the prevention of CVD, though interindividual differences in the response to n-3 PUFAs have been observed. We aimed to

  14. Apolipoprotein E-mimetics inhibit neurodegeneration and restore cognitive functions in a transgenic Drosophila model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Svetlana Sarantseva

    Full Text Available BACKGROUND: Mutations of the amyloid precursor protein gene (APP are found in familial forms of Alzheimer's disease (AD and some lead to the elevated production of amyloid-beta-protein (Abeta. While Abeta has been implicated in the causation of AD, the exact role played by Abeta and its APP precursor are still unclear. PRINCIPAL FINDINGS: In our study, Drosophila melanogaster transgenics were established as a model to analyze AD-like pathology caused by APP overexpression. We demonstrated that age related changes in the levels and pattern of synaptic proteins accompanied progressive neurodegeneration and impairment of cognitive functions in APP transgenic flies, but that these changes may be independent from the generation of Abeta. Using novel peptide mimetics of Apolipoprotein-E, COG112 or COG133 proved to be neuroprotective and significantly improved the learning and memory of APP transgenic flies. CONCLUSIONS: The development of neurodegeneration and cognitive deficits was corrected by injections of COG112 or COG133, novel mimetics of apolipoprotein-E (apoE with neuroprotective activities.

  15. Effect of Mediterranean diet with and without weight loss on apolipoprotein B100 metabolism in men with metabolic syndrome

    Science.gov (United States)

    The objective of this study was to assess the effect of a Mediterranean diet (MedDiet) with and without weight loss (WL) on apolipoprotein B100 (apoB100) metabolism in men with metabolic syndrome. The diet of 19 men with metabolic syndrome (age, 24–62 years) was first standardized to a North America...

  16. The apolipoprotein E epsilon4-allele and antihypertensive treatment are associated with increased risk of cerebral MRI white matter hyperintensities

    DEFF Research Database (Denmark)

    Høgh, P; Garde, Ellen; Mortensen, Erik Lykke;

    2007-01-01

    OBJECTIVE: Apolipoprotein E-epsilon4 (APOE-epsilon4) is a potential risk factor for cerebral vascular disease. The aim of the present study was to examine the relative importance of APOE-epsilon4 and other relevant risk factors for the extent of cerebral white matter hyperintensity (WMH) in a...

  17. The intravenous injection of oxidized LDL- or Apolipoprotein B100 – Coupled splenocytes promotes Th1 polarization in wildtype and Apolipoprotein E – Deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Steinmetz, Martin, E-mail: martin.steinmetz@ukb.uni-bonn.de [INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris (France); Internal Medicine II, University Hospital Bonn, 53105 Bonn (Germany); Ponnuswamy, Padmapriya; Laurans, Ludivine; Esposito, Bruno; Tedgui, Alain [INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris (France); Mallat, Ziad [INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris (France); Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke' s Hospital, Cambridge, CB2 2QQ (United Kingdom)

    2015-08-14

    Background: Th1 responses in atherosclerosis are mainly associated with the aggravation of atherosclerotic plaques, whereas Th2 responses lead to a less pronounced disease in mouse models. The fixation of antigens on cells by means of ethylene carbodiimide (ECDI), and subsequent injection of these antigen-coupled splenocytes (Ag-SP) to induce tolerance against the attached antigens, has been successfully used to treat murine type 1 diabetes or encephalomyelitis in. We analyzed this approach in a mouse model for atherosclerosis. Methods and results: OTII-transgenic mice that were treated with a single dose of 5 × 10{sup 7} OVA-coupled splenocytes (OVA-SP), had decreased splenocyte proliferation, and lower IFNγ production in vitro upon antigen recall. However, in vivo CD4 cell activation was increased. To try lipoprotein-derived, “atherosclerosis-associated” antigens, we first tested human oxidized LDL. In wild type mice, an increase of IFNγ production upon in vitro recall was detected in the oxLDL-SP group. In Apolipoprotein E − deficient (ApoE−/−) mice that received oxLDL-SP every 5 weeks for 20 weeks, we did not find any difference of atherosclerotic plaque burden, but again increased IFNγ production. To overcome xenogenous limitations, we then examined the effects of mouse Apolipoprotein B100 peptides P3 and P6. ApoB100-SP treatment again promoted a more IFNγ pronounced response upon in vitro recall. Flow cytometry analysis of cytokine secreting spleen cells revealed CD4 positive T cells to be mainly the source for IFNγ. In ApoE−/− mice that were administered ApoB100-SP during 20 weeks, the atherosclerotic plaque burden in aortic roots as well as total aorta was unchanged compared to PBS treated controls. Splenocyte proliferation upon antigen recall was not significantly altered in ApoB100-SP treated ApoE−/− mice. Conclusion: Although we did not observe a relevant anti-atherosclerotic benefit, the treatment with antigen

  18. The intravenous injection of oxidized LDL- or Apolipoprotein B100 – Coupled splenocytes promotes Th1 polarization in wildtype and Apolipoprotein E – Deficient mice

    International Nuclear Information System (INIS)

    Background: Th1 responses in atherosclerosis are mainly associated with the aggravation of atherosclerotic plaques, whereas Th2 responses lead to a less pronounced disease in mouse models. The fixation of antigens on cells by means of ethylene carbodiimide (ECDI), and subsequent injection of these antigen-coupled splenocytes (Ag-SP) to induce tolerance against the attached antigens, has been successfully used to treat murine type 1 diabetes or encephalomyelitis in. We analyzed this approach in a mouse model for atherosclerosis. Methods and results: OTII-transgenic mice that were treated with a single dose of 5 × 107 OVA-coupled splenocytes (OVA-SP), had decreased splenocyte proliferation, and lower IFNγ production in vitro upon antigen recall. However, in vivo CD4 cell activation was increased. To try lipoprotein-derived, “atherosclerosis-associated” antigens, we first tested human oxidized LDL. In wild type mice, an increase of IFNγ production upon in vitro recall was detected in the oxLDL-SP group. In Apolipoprotein E − deficient (ApoE−/−) mice that received oxLDL-SP every 5 weeks for 20 weeks, we did not find any difference of atherosclerotic plaque burden, but again increased IFNγ production. To overcome xenogenous limitations, we then examined the effects of mouse Apolipoprotein B100 peptides P3 and P6. ApoB100-SP treatment again promoted a more IFNγ pronounced response upon in vitro recall. Flow cytometry analysis of cytokine secreting spleen cells revealed CD4 positive T cells to be mainly the source for IFNγ. In ApoE−/− mice that were administered ApoB100-SP during 20 weeks, the atherosclerotic plaque burden in aortic roots as well as total aorta was unchanged compared to PBS treated controls. Splenocyte proliferation upon antigen recall was not significantly altered in ApoB100-SP treated ApoE−/− mice. Conclusion: Although we did not observe a relevant anti-atherosclerotic benefit, the treatment with antigen-coupled splenocytes

  19. Metabolism of apolipoproteins C-II, C-III, and B in hypertriglyceridemic men. Changes after heparin-induced lipolysis

    International Nuclear Information System (INIS)

    The C apolipoproteins are normally transferred to high density lipoproteins (HDL) after lipolysis of very low density lipoprotein (VLDL) triglyceride. In previous studies, a loss of plasma C apolipoproteins was documented after heparin-induced lipolysis in hypertriglyceridemic subjects. The present studies were designed to determine if this decline in plasma C apolipoproteins was due to their clearance with VLDL remnants. Five Type IV hypertriglyceridemic and two normal subjects were injected with 125I-VLDL and 131I-low density lipoproteins (LDL) to document kinetically an excess of VLDL apolipoprotein (apo) B flux relative to LDL apo B flux in the Type IV subjects. A mean of 46% VLDL apo B was cleared from the circulation, without conversion to intermediate density lipoprotein (IDL) or LDL. Heparin was then infused (9000 IU over 4 hours) to generate an excess of VLDL remnants that were not converted to IDL or LDL. VLDL triglyceride, apo B, and apo C concentrations fell at a similar rate. VLDL apo B declined by 42% (p less than 0.01). However, no increases were observed in IDL or LDL apo B in the Type IV subjects. This resulted in a 14% (p less than 0.01) decline in plasma apo B concentrations, indicating a clearance of VLDL remnants. VLDL apo C-II and C-III concentrations fell by 42% (p less than 0.025) and 52% (p less than 0.01), respectively. During the first 2.5 hours of infusion, they were almost quantitatively recovered in HDL. Thereafter, the C apolipoproteins declined in HDL during which time VLDL apo C concentrations continued to decline

  20. Metabolism of apolipoproteins C-II, C-III, and B in hypertriglyceridemic men. Changes after heparin-induced lipolysis

    Energy Technology Data Exchange (ETDEWEB)

    Huff, M.W.; Breckenridge, W.C.; Strong, W.L.; Wolfe, B.M.

    1988-09-01

    The C apolipoproteins are normally transferred to high density lipoproteins (HDL) after lipolysis of very low density lipoprotein (VLDL) triglyceride. In previous studies, a loss of plasma C apolipoproteins was documented after heparin-induced lipolysis in hypertriglyceridemic subjects. The present studies were designed to determine if this decline in plasma C apolipoproteins was due to their clearance with VLDL remnants. Five Type IV hypertriglyceridemic and two normal subjects were injected with 125I-VLDL and 131I-low density lipoproteins (LDL) to document kinetically an excess of VLDL apolipoprotein (apo) B flux relative to LDL apo B flux in the Type IV subjects. A mean of 46% VLDL apo B was cleared from the circulation, without conversion to intermediate density lipoprotein (IDL) or LDL. Heparin was then infused (9000 IU over 4 hours) to generate an excess of VLDL remnants that were not converted to IDL or LDL. VLDL triglyceride, apo B, and apo C concentrations fell at a similar rate. VLDL apo B declined by 42% (p less than 0.01). However, no increases were observed in IDL or LDL apo B in the Type IV subjects. This resulted in a 14% (p less than 0.01) decline in plasma apo B concentrations, indicating a clearance of VLDL remnants. VLDL apo C-II and C-III concentrations fell by 42% (p less than 0.025) and 52% (p less than 0.01), respectively. During the first 2.5 hours of infusion, they were almost quantitatively recovered in HDL. Thereafter, the C apolipoproteins declined in HDL during which time VLDL apo C concentrations continued to decline.

  1. Apolipoprotein B-100 Hopkins (arginine4019 → tryptophan): A new apolipoprotein B-100 variant in a family with premature atherosclerosis and hyperapobetalipoproteinemia

    International Nuclear Information System (INIS)

    A 43-year-old woman with severe coronary artery disease and hyperapobetalipoproteinemia was heterozygous for an abnormal Msp I apolipoprotein B (APOB) gene fragment because of the absence of the Msp I site around codon 4046 in exon 29 of the APOB gene. Using the polymerase chain reaction technique, 134 base pairs containing the mutant Msp I site were amplified, cloned, and sequenced. The mutation was a C to T transition, substituting tryptophan for arginine at amino acid position 4019 of the mature ApoB-100 protein. Seven relatives of the proband has the same mutation, which has been called ApoB-100 Hopkins. Only three of seven relatives with the mutation had hyperapobetalipoproteinemia. Mutant low-density lipoprotein (LDL) was bound and degraded to a greater extent than normal LDL in cultured human fibroblasts. In conclusion, a new mutation, ApoB-100 Hopkins, was not linked to the hyperapobetalipoproteinemia phenotype, which also was segregating in this family. The increased affinity of this mutant LDL for the LDL receptor may be due to a specific effect of ApoB-100 Hopkins or to altered LDL size and composition

  2. Apolipoprotein B-100 Hopkins (arginine sub 4019 yields tryptophan): A new apolipoprotein B-100 variant in a family with premature atherosclerosis and hyperapobetalipoproteinemia

    Energy Technology Data Exchange (ETDEWEB)

    Ladias, J.A.A.; Kwiterovich, P.O. Jr.; Smith, H.H.; Miller, M.; Bachorik, P.S.; Antonarakis, S.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA)); Forte, T. (Univ. of California, Los Angeles (USA)); Lusis, A.J. (Donner Laboratory, Berkeley, CA (USA))

    1989-10-13

    A 43-year-old woman with severe coronary artery disease and hyperapobetalipoproteinemia was heterozygous for an abnormal Msp I apolipoprotein B (APOB) gene fragment because of the absence of the Msp I site around codon 4046 in exon 29 of the APOB gene. Using the polymerase chain reaction technique, 134 base pairs containing the mutant Msp I site were amplified, cloned, and sequenced. The mutation was a C to T transition, substituting tryptophan for arginine at amino acid position 4019 of the mature ApoB-100 protein. Seven relatives of the proband has the same mutation, which has been called ApoB-100 Hopkins. Only three of seven relatives with the mutation had hyperapobetalipoproteinemia. Mutant low-density lipoprotein (LDL) was bound and degraded to a greater extent than normal LDL in cultured human fibroblasts. In conclusion, a new mutation, ApoB-100 Hopkins, was not linked to the hyperapobetalipoproteinemia phenotype, which also was segregating in this family. The increased affinity of this mutant LDL for the LDL receptor may be due to a specific effect of ApoB-100 Hopkins or to altered LDL size and composition.

  3. Selective oxidation of methionine residues in apolipoprotein A-I and its potential biological consequences

    International Nuclear Information System (INIS)

    The earliest stages of HDL oxidation are accompanied by the oxidation of specific Met residues in apolipoprotein AI and AII and the formation of Met sulfoxides (Met(O)) has been proposed to play a significant role in the reduction and hence detoxification of lipid hydroperoxides associated with HDL. Oxidation of HDL may generally decrease the anti-atherogenic properties of this lipoprotein, although both, the inhibition and the enhancement of cholesterol removal from cells has been reported for different types of oxidation. In light of these findings we have investigated the secondary structure, lipid affinity, LCAT activation and cholesterol-efflux promoting properties of native and selectively oxidized apo A-I(apo A-I+32, containing Met(O) at Metl12 and Metl48) in purified or reconstituted forms. Data obtained by circular dichroism revealed that selective oxidation of Met residues 112 and 148 does not alter alpha helicity of the protein in solution, indicating that this oxidation is not sufficient to influence significantly this type of secondary structure of apo A-I in its 'lipid-free' form. The lipid affinity of native apo A-I and apo A-I+32 was determined as the rate of clearance of DMPC multilamellar to small unilamellar vesicles. Compared with the native protein, apo A-I+32 induced a 2-3 fold faster rate of clearance, suggesting that the increased hydrophilicity due Met(O) increased the rate for protein-lipid interactions. Met residues 112 and 148 reside in the hydrophobic faces of helices 5 and 7, and both these regions have been suggested to be important for both, LCAT activation and cholesterol efflux. Kinetic experiments have revealed that the affinity for LCAT is comparable for HDL reconstituted with either apo A-I or apo A-I+32. Efflux of [3H]-cholesterol from lipid-laden human monocytederived macrophages to isolated apolipoproteins was enhanced for apo A-I+32 compared with apo A-I, consistent with the DMPC clearance data. Together these findings

  4. Meta-analysis for the Association of Apolipoprotein E ε2/ε3/ε4 Polymorphism with Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    Yong Zhang; Hai-Qin Tang; Wen-Jia Peng; Bing-Bing Zhang; Ming Liu

    2015-01-01

    Background:Coronary heart disease (CHD) is a multifactorial disease and is thought to have a polygenic basis.Apolipoprotein E (APOE) gene is one such candidate with its common ε2/ε3/ε4 polymorphism in CHD.In recent years,numerous case-control studies have investigated the relationship ofAPOE polymorphism with CHD risk.However,the results are confusing.Methods:To clarify this point,we undertook a meta-analysis based on 14 published studies including 5746 CHD cases and 19,120 controls.Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for association using a random-effects or fixed-effects model using STATA version 10 (StataCorp LP,College Station,TX,USA).Results:Overall,the analysis showed that carriers of APOE ε2 allele decreased risk for CHD (ε2 allele vs.ε3 allele:OR =0.82,95% CI:0.75-0.90,P < 0.001;ε2 carriers vs.ε3 carriers:OR =0.81,95% CI:0.73-0.89,P < 0.001),compared with those carrying ε3 allele,especially in Caucasian population.However,those with ε4 allele had a significant increased risk for CHD (ε4 allele vs.ε3 allele:OR =1.34,95% CI:1.15-1.57,P < 0.001),especially in Mongoloid population.Potential publication bias was observed in the genetic model of ε4 versus ε3,but the results might not be affected deeply by the publication bias.When we accounted for publication bias using the trim and fill method,the results were not materially alerted,suggesting the stability of our results.Conclusions:Taken together,our meta-analysis supported a genetic association between APOE gene and CHD.ε4 increased the risk of CHD,whereas ε2 decreased the risk of CHD.

  5. Cable Stability

    CERN Document Server

    Bottura, L

    2014-01-01

    Superconductor stability is at the core of the design of any successful cable and magnet application. This chapter reviews the initial understanding of the stability mechanism, and reviews matters of importance for stability such as the nature and magnitude of the perturbation spectrum and the cooling mechanisms. Various stability strategies are studied, providing criteria that depend on the desired design and operating conditions.

  6. Apolipoprotein M

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2013-01-01

    chaperone for S1P. S1P is a bioactive lipid with effects on angiogenesis, lymphocyte trafficking, endothelial cell migration, and inflammation. A drug targeting the S1P-system (fingolimod) is now used for treatment of multiple sclerosis. It improves the blood–brain barrier and inhibits migration of...

  7. Association of Serum Apolipoprotein B with the Increased Risk of Diabetes in Korean Men

    Science.gov (United States)

    Lim, Hyo Hee

    2016-01-01

    This study aimed to investigate the association of Apolipoprotein B (ApoB) with the risk of diabetes in Koreans. Korean men (n = 790, 40-79 years) who had been never diagnosed for diabetes before participating were enrolled. Subjects were categorized into normal fasting glucose (NFG, n = 519), impaired fasting glucose (IFG, n = 188) and newly-onset diabetes (n = 83) according to fasting glucose levels. Age was not significantly different among the subgroups. Mean values of BMI, waist circumference, Blood pressure(BP), triglyceride, non-HDL cholesterol were significantly higher in IFG or newly-onset diabetic subjects compared to NFG subjects. The levels of glucose, insulin, free fatty acid, insulin resistance and ApoB were highest in diabetic patients and lowest in NFG subjects. According to ApoB level, subjects were divided into two groups (high-ApoB group: ≥ 87.0 mg/dL vs. low-ApoB group: Korean men.

  8. Study on relationship of apolipoprotein E gene polymorphism and genetic susceptibility of stress urinary incontinence

    Institute of Scientific and Technical Information of China (English)

    Tong Jia-li; Lang Jing-he; Zhu lan

    2010-01-01

    Objective: To explore the relationship between apolipoprotein E (ApoE) gene polymorphism and susceptibility of stress urinary incontinence (SUI).Methods: ApoE genotypes were examined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) technique in 99 patients with SUI and 101 asymptomatic controls. Results: The frequency of allele e3 of ApoE was slightly lower in patients with anatomic SUI than that in controls (79.44% vs. 81.68%), while the frequency of allele e4 of ApoE was slightly higher in patients with anatomic SUI than that in controls (10.00% vs. 9.90%). No significant difference was found in frequency of allele e3 or e4 between SUI patients and controls (χ2=0.523, P=0.770).Conclusion: The gene polymorphism of ApoE is not independently involved in the development of SUI.

  9. Production and Analysis of Biological Properties of Recombinant Human Apolipoprotein A-I.

    Science.gov (United States)

    Ryabchenko, A V; Kotova, M V; Tverdohleb, N V; Knyazev, R A; Polyakov, L M

    2015-11-01

    Production of recombinant human apolipoprotein A-I (apoA-I) in E. coli cells is described and its biological properties are compared with those of natural protein. Recombinant apoA-I was isolated as a chimeric polypeptide and then processed to a mature form apoA-I (rapo-I). We studied the ability of the resulting protein to penetrate into hepatocyte nuclei and regulate the rate of DNA biosynthesis in complex with estriol. Penetration of rapoA-I conjugated with FITC into hepatocyte nuclei was demonstrated. rapoA-I-estriol and apoA-I-estriol complexes induced similar increase in DNA biosynthesis rate in isolated hepatocytes, which confi rms functional similarity of the obtained recombinant mature protein (rapoA-I) and native human apoA-I. PMID:26612626

  10. Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation

    Science.gov (United States)

    Borhani, David W.; Rogers, Danise P.; Engler, Jeffrey A.; Brouillette, Christie G.

    1997-01-01

    The structure of truncated human apolipoprotein A-I (apo A-I), the major protein component of high density lipoprotein, has been determined at 4-Å resolution. The crystals comprise residues 44–243 (exon 4) of apo A-I, a fragment that binds to lipid similarly to intact apo A-I and that retains the lipid-bound conformation even in the absence of lipid. The molecule consists almost entirely of a pseudo-continuous, amphipathic α-helix that is punctuated by kinks at regularly spaced proline residues; it adopts a shape similar to a horseshoe of dimensions 125 × 80 × 40 Å. Four molecules in the asymmetric unit associate via their hydrophobic faces to form an antiparallel four-helix bundle with an elliptical ring shape. Based on this structure, we propose a model for the structure of apo A-I bound to high density lipoprotein. PMID:9356442

  11. Sex, but not Apolipoprotein E Polymorphism, Differences in Spatial Performance in Young Adults.

    Science.gov (United States)

    Yasen, Alia L; Raber, Jacob; Miller, Jeremy K; Piper, Brian J

    2015-11-01

    The purpose of this study was to examine how sex and apolipoprotein E (APOE) genotype contribute to individual differences in spatial learning and memory. The associations of APOE genotype with neurocognitive function have been well studied among the elderly but less is known at earlier ages. Young adults (n = 169, 88 females) completed three neurocognitive tasks: mental rotation, spatial span, and Memory Island, a spatial navigation test. Males outperformed females on all three tasks: finding the hidden targets more quickly on Memory Island (Cohen's d = 0.62) and obtaining higher scores on mental rotation (d = 0.54) and spatial span (d = 0.37). In contrast, no significant effects of APOE were observed. The identified sex differences elaborate upon past literature documenting sexually dimorphic performance on specific neurobehavioral tasks. PMID:25750133

  12. Identification of liver receptor homolog-1 as a novel regulator of apolipoprotein AI gene transcription.

    Science.gov (United States)

    Delerive, Philippe; Galardi, Cristin M; Bisi, John E; Nicodeme, Edwige; Goodwin, Bryan

    2004-10-01

    The orphan nuclear receptor liver receptor homolog-1 (LRH-1) has been reported to play a role in bile acid biosynthesis and reverse cholesterol transport. In this study, we examined the role of LRH-1 in the regulation of the apolipoprotein AI (APOAI) gene. Using RNA interference and adenovirus-mediated overexpression, we show that LRH-1 directly regulates APOAI gene transcription. Transient transfection experiments and EMSAs revealed that LRH-1 directly regulates APOAI transcription by binding to an LRH-1 response element located in the proximal APOAI promoter region. Chromatin immunoprecipitation experiments revealed that LRH-1 binds to the human APO AI promoter in vivo. Finally, we show that the transcriptional repressor SHP (small heterodimer partner) suppressed APOAI gene expression by inhibiting LRH-1 transcriptional activity. Taken together, our results demonstrate that LRH-1 is a novel regulator of APOAI transcription and underscore the role of this receptor in cholesterol homeostasis. PMID:15218078

  13. Impact of psychological stress on the associations between apolipoprotein E variants and metabolic traits: findings in an American sample of caregivers and controls

    DEFF Research Database (Denmark)

    Kring, Sofia Iqbal; Brummett, Beverly H; Barefoot, John;

    2010-01-01

    To examine the association between apolipoprotein E (APOE) gene variants and waist circumference, fasting plasma glucose, serum insulin, serum high-density lipoprotein cholesterol, and serum triglycerides, all metabolic traits known as cardiovascular disease (CVD) endophenotypes, in a population ...

  14. A strategy for solubilizing delipidated apolipoprotein with lysophosphatidylcholine and reconstitution with phosphatidylcholine

    International Nuclear Information System (INIS)

    The apolipoproteins of insect lipophorin were dissociated in guanidinium chloride and isolated by gel permeation chromatography. Over 98% of the total lipid in lipophorin was associated with apolipophorin I (apoLp-I), thus suggesting this apolipoprotein to be the lipid binding component of the particle. ApoLp-I was delipidated with ethanol/ether and solubilized in buffer that contained radioactive lysophosphatidylcholine ([3H]LPC) above the critical micellar concentration. Sonic irradiation of radioactive phosphatidylcholine ([14C]PC) with [3H]LPC-solubilized apoLp-I at a molar ratio of 318 resulted in reconstituted lipophorin I (RLp-I). [3H]LPC was bound to fatty acid free bovine serum albumin and was separated from RLp-I by density gradient ultracentrifugation and gel permeation chromatography. Negatively stained RLp-I particles were quasispherical with an average radius of 55 angstrom, and their overall morphology and secondary structure were similar to those of native hemolymph lipophorin. The RLp-I particle had a ρ = 1.137 g/mL, a Mr ∼ 5.2 x 105, and a [14C]PC:apoLp-I molar ratio of 308. From the compositional analysis, molecular size, trypsinization, and lipolysis with phospholipase A2, the authors concluded that each RLp-I particle contained one molecule of apoLp-I and a monomolecular layer of [14C]PC. When injected into the hemolymph of adult moths in vivo, RLp-I was loaded with lipid, as judged by a decrease in its density both in the presence and in the absence of adipokinetic hormone. The similarities in morphology and immunology of RLp-I and native lipophorin, together with the ability of RLp-I to load lipid, suggest that reconstituted lipophorins may serve as models to probe lipophorin structure and function

  15. A strategy for solubilizing delipidated apolipoprotein with lysophosphatidylcholine and reconstitution with phosphatidylcholine

    Energy Technology Data Exchange (ETDEWEB)

    Kawooya, J.K.; Wells, M.A.; Law, J.H. (Univ. of Arizona, Tucson (USA))

    1989-08-08

    The apolipoproteins of insect lipophorin were dissociated in guanidinium chloride and isolated by gel permeation chromatography. Over 98% of the total lipid in lipophorin was associated with apolipophorin I (apoLp-I), thus suggesting this apolipoprotein to be the lipid binding component of the particle. ApoLp-I was delipidated with ethanol/ether and solubilized in buffer that contained radioactive lysophosphatidylcholine (({sup 3}H)LPC) above the critical micellar concentration. Sonic irradiation of radioactive phosphatidylcholine (({sup 14}C)PC) with ({sup 3}H)LPC-solubilized apoLp-I at a molar ratio of 318 resulted in reconstituted lipophorin I (RLp-I). ({sup 3}H)LPC was bound to fatty acid free bovine serum albumin and was separated from RLp-I by density gradient ultracentrifugation and gel permeation chromatography. Negatively stained RLp-I particles were quasispherical with an average radius of 55{angstrom}, and their overall morphology and secondary structure were similar to those of native hemolymph lipophorin. The RLp-I particle had a {rho} = 1.137 g/mL, a M{sub r} {approx} 5.2 x 10{sup 5}, and a ({sup 14}C)PC:apoLp-I molar ratio of 308. From the compositional analysis, molecular size, trypsinization, and lipolysis with phospholipase A{sub 2}, the authors concluded that each RLp-I particle contained one molecule of apoLp-I and a monomolecular layer of ({sup 14}C)PC. When injected into the hemolymph of adult moths in vivo, RLp-I was loaded with lipid, as judged by a decrease in its density both in the presence and in the absence of adipokinetic hormone. The similarities in morphology and immunology of RLp-I and native lipophorin, together with the ability of RLp-I to load lipid, suggest that reconstituted lipophorins may serve as models to probe lipophorin structure and function.

  16. Elevated hepatic apolipoprotein A-I transcription is associated with diet-induced hyperalphalipoproteinemia in rabbits.

    Science.gov (United States)

    Schwab, D A; Rea, T J; Hanselman, J C; Bisgaier, C L; Krause, B R; Pape, M E

    2000-03-24

    Past studies have shown that a high saturated fatty acid diet containing coconut oil elevates plasma HDL cholesterol and apolipoprotein A-I (apoA-1) in rabbits through a mechanism involving increased synthesis. We have extended those studies by investigating expression of the hepatic apolipoprotein A-I gene and other lipid related genes in that model. Rabbits fed a diet containing 14% coconut oil for 4 weeks showed HDL-C elevations of 170% to 250% over chow-fed controls with peak differences occurring at 1 week. Plasma apoA-I levels were also increased over this time frame (160% to 180%) reflecting the HDL-C changes. After 4 weeks, there were no differences in plasma VLDL-C or LDL-C levels in chow versus coconut oil-fed rabbits. Hepatic levels of apoA-I mRNA in coconut oil-fed animals were elevated 150% after 4 weeks compared to chow-fed controls; hepatic mRNA levels for ten other genes either decreased slightly (apoB, LCAT, hepatic lipase, albumin, ACAT, and HMG CoA reductase) or were unchanged (CETP, apoE, LDL-receptor, and acyl CoA oxidase). Nuclear run-on transcription assays revealed that coconut oil feeding for 4 weeks caused a 220% increase in hepatic apoA-I transcription rate compared to controls; no change was observed for CETP and apoE. Treatment of cultured rabbit liver cells with various saturated fatty acids and sera from chow-fed and coconut oil-fed rabbits did not alter apoA-I mRNA levels as observed in vivo. These data demonstrate that coconut oil elevates plasma HDL-C and apoA-I by increasing hepatic apoA-I transcription while expression of other genes involved in lipid metabolism are reduced or unchanged in response to coconut oil feeding. PMID:10809165

  17. A cDNA-dependent scintillation proximity assay for quantifying apolipoprotein A-I.

    Science.gov (United States)

    Hanselman, J C; Schwab, D A; Rea, T J; Bisgaier, C L; Pape, M E

    1997-11-01

    We have developed a cDNA-dependent scintillation proximity assay (SPA) for rabbit apolipoprotein A-I that follows a classic radioimmunoassay scheme, in that antiserum and radiolabeled ligand are used in a process to quantify a source containing unlabeled ligand. To synthesize radiolabeled ligand we isolated a full-length rabbit apolipoprotein A-I (apoA-I) cDNA, transcribed the corresponding RNA in vitro, and synthesized radiolabeled apoA-I by including tritiated leucine in an in vitro translation reaction. Assay conditions were established which allowed quantification of unlabeled apoA-I over a range of 0.2 to 4 nanograms with intra- and interassay coefficients of variation of 5% and 10%, respectively. Purified rabbit apoA-I, apoA-I in rabbit liver parenchymal cell conditioned media, and apoA-I contained in rabbit plasma all generated parallel titration curves. Quantification of rabbit plasma apoA-I was not affected when sheep anti-rabbit apoA-I serum was mixed with sheep anti-rabbit apoB or apoE serum; thus, the antibody need not be specific to quantify the ligand of interest. To show utility of the assay, apoA-I mass was quantified in in vitro and in vivo models displaying altered apoA-I levels. In each model apoA-I values from the cDNA-dependent SPA and the established methodologies of Western blotting and electroimmunodiffusion were highly correlated. The approach outlined in this report should permit rapid development of scintillation proximity assays for other proteins given the widespread availability of full-length cDNAs. PMID:9392434

  18. Clinical, biopsy, and mass spectrometry characteristics of renal apolipoprotein A-IV amyloidosis.

    Science.gov (United States)

    Dasari, Surendra; Amin, Md Shahrier; Kurtin, Paul J; Vrana, Julie A; Theis, Jason D; Grogg, Karen L; Alexander, Mariam P; Nasr, Samih H; Fervenza, Fernando C; Leung, Nelson; Sethi, Sanjeev

    2016-09-01

    Apolipoprotein A-IV associated amyloidosis (AApoAIV amyloidosis) is a rare cause of amyloidosis with only a single reported case. Here we describe the clinical, biopsy, and mass spectrometry characteristics of 11 cases of renal AApoAIV amyloidosis encompassing 9 men and 2 women with a mean age at diagnosis of 63.5 years. Progressive chronic kidney disease (mean serum creatinine 2.9 mg/dl) was the most common cause for biopsy with proteinuria absent or minimal in all except one. Hematological and serological evaluation was negative in 9 patients, while 2 had a monoclonal gammopathy. The renal biopsy findings were striking and showed large amounts of eosinophilic Congo-red positive amyloid deposits restricted to the renal medulla with sparing of the renal cortex. In 6 cases, peritubular amyloid was noted in addition to the interstitial involvement. Immunofluorescence studies were negative for immunoglobulins. Electron microscopy showed nonbranching fibrils measuring 7 to 10 nm in diameter. Laser microdissection of the amyloid deposits followed by mass spectrometry showed large spectra number (a semiquantitative measure of abundance) for AApoAIV protein ranging from 49 to 169 (average 85), serum amyloid protein (average 19), and apolipoprotein E (average 48). Importantly, no peptides were detected for any other forms of known amyloidogenic precursor proteins. Thus, renal AApoAIV amyloidosis typically presents with progressive chronic kidney disease and histologically exhibits extensive medullary involvement with sparing of the cortex. The diagnosis is best established by mass spectrometry. Hence, a high degree of suspicion and examination of the renal medulla is required to make the diagnosis. PMID:27262366

  19. Enhanced Diabetes Susceptibility in Community Dwelling Han Elders Carrying the Apolipoprotein E 3/3 Genotype.

    Science.gov (United States)

    Ban, Chun-Xia; Zhong, Li; Wang, Tao; Zhu, Min-Jie; Wang, Jing-Hua; Zhang, Zhen-Lian; Wang, Zhe; Su, Ning; Liu, Yuan-Yuan; Shi, Yan-Chen; Xiao, Shi-Fu; Li, Xia

    2016-01-01

    Despite Apolipoprotein E (ApoE) being one of the main apolipoproteins in the blood, the association between its genotype and the high cholesterol or blood glucose levels commonly seen in clinical practice is inconclusive. Such research is also lacking in the Han population. The aim of this study was to investigate the association between APOE genotype, diabetes, and plasma glucose and lipid levels. We included 243 community-dwelling elderly residents in this study. Participant APOE genotypes were assessed and were simultaneously tested for weight, height, blood glucose, triglycerides, cholesterol, and high- and low-density lipoprotein. In addition, gender, age, years of education, cognitive function, and medical history was recorded. Subjects were divided into 3 groups based on APOE genotype: APOE ε2 group (ε2/ε2 and ε2/ε3), APOE ε3 group (ε3/ε3), and APOE ε4 group (ε2/ε4, ε3/ε4 and ε4/ε4). Comparisons between groups were conducted for the incidence of diabetes, high blood pressure, and dementia, as well as for differences in body-mass index, fasting plasma glucose, and blood lipids. The APOE ε3/ε3 genotype exhibited the highest frequency (70.4%) among the subjects. Participants in the APOE ε3 group demonstrated significantly higher levels of fasting plasma glucose than those in the APOE ε2 and APOE ε4 groups (Pfasting plasma glucose values than did the APOE ε2 group (P = 0.065). Furthermore, the APOE3 genotype was significantly correlated with both fasting plasma glucose level and glucose abnormality (P< 0.05) and trended toward statistically significant correlation with diabetes (P = 0.082). The correlation between APOE2 and low low-density lipoprotein levels also approached statistical significance (P = 0.052). Thus, elderly community dwelling residents of Han ethnicity carrying the APOE ε3/ε3 genotype might have higher plasma glucose levels and a higher occurrence of diabetes. PMID:26998902

  20. Characterization of the apolipoprotein AI and CIII genes in the domestic pig

    Energy Technology Data Exchange (ETDEWEB)

    Birchbauer, A.; Knipping, G.; Juritsch, B.; Zechner, R. (Univ. of Graz (Austria)); Aschauer, H. (Sandoz-Forschungs Institut Ges.m.b.H., Vienna (Austria))

    1993-03-01

    The apolipoproteins (apo) AI and CIII are important constituents of triglyceride-rich lipoproteins and high-density lipoproteins. In humans, apo AI is believed to play an important protective role in the pathogenesis of arteriosclerosis, whereas apo CIII might be involved in the development of hypertriglyceridemia. Both human genes are located within a gene cluster on chromosome 11. Although the domestic pig has been widely used as an animal model in arteriosclerosis and lipid research, the porcine apolipoproteins genes are poorly characterized. In this report, the complete nucleotide sequences of the porcine apo AI and CIII genes are presented and the authors demonstrate, for the first time, apo CIII expression in the pig. Both genes are composed of four exons and three introns and resemble closely their human counterparts with regard to the transcriptional start sites, exon sizes, intron sizes, exon-intron borders, and the size of the intergenic region. The predicted pig apo AI is a protein of 241 amino acids, which is 2 amino acids shorter than human apo AI. The protein sequence was found to be very homologous to apo AI sequences in other mammalian species. Apo AI expression was detected on the mRNA level in porcine liver and intestine. The apo CIII gene encodes a protein with 73 amino acids, which is 6 amino acids shorter than human apo CIII. In contrast to the three isoforms of apo CIII found in humans, only one major isoform was detected in the pig. Presumably this isoform is unglycosylated. In addition to apo CIII expression in the liver and the intestine, a truncated form of apo CIII mRNA was also found in porcine kidney. The studies demonstrate the presence of an apo CIII gene, an apo CIII mRNA, and an apo CIII protein in the pig and, therefore, exclude a hypothesized apo CIII deficiency in these animals. 53 refs., 5 figs.

  1. FTY720 Attenuates Acute Pancreatitis in Hypertriglyceridemic Apolipoprotein CIII Transgenic Mice.

    Science.gov (United States)

    Liu, Jinjiao; Xu, Pengfei; Zhang, Ling; Kayoumu, Abudurexiti; Wang, Yunan; Wang, Mengyu; Gao, Mingming; Zhang, Xiaohong; Wang, Yuhui; Liu, George

    2015-09-01

    Hypertriglyceridemic pancreatitis (HTGP) is often encountered clinically as a common form of recurrent acute pancreatitis (AP). It is important to evaluate the management of severe hypertriglyceridemia (HTG) or anti-inflammation in the prophylaxis of HTGP in the clinic. FTY720 (2-amino-2[2-(4-octylphenyl) ethyl]-1, 3-propanediol) is a new anti-inflammatory agent with low toxicity and reported to ameliorate lung injury with pancreatitis in rat. We evaluated its protective affection on AP induced by seven hourly intraperitoneal injection of cerulein in apolipoprotein CIII transgenic mice with severe HTG. FTY720 at 1.5 mg/kg was administered by gastric lavage daily for 3 days before induction of AP. The effects of FTY720 to protect against HTGP were assessed by serum amylase, pancreatic pathological scores, immunostaining, and the expression of inflammatory cytokine genes. As a result, injection of cerulein resulted in more severe pathological changes of AP and higher monocyte chemoattractant protein 1 expression in the pancreas in transgenic than in nontransgenic mice. FTY720 pretreatment improved the pathological severity of AP and decreased the expression of monocyte chemoattractant protein 1 in the pancreas significantly, especially near fourfold reduction in transgenic mice. However, FTY720 did not affect plasma triglyceride levels, and other inflammatory factors and plasma amylase were not correlated with the extent of pancreatic damage in AP with or without FTY720 administration. In summary, our study in a new model, apolipoprotein CIII transgenic mice, demonstrated that HTG mice are susceptible to induction of AP. Prophylactic treatment of FTY720 can significantly attenuate cerulein-induced AP and hence warrant further investigation of sphingosine-1-phosphate receptors agonist for potential clinical application in recurrent attacks of HTGP. PMID:25944794

  2. Serum apolipoproteins in relation to intakes of fish in population of Arkhangelsk County

    Directory of Open Access Journals (Sweden)

    Petrenya Natalia

    2012-06-01

    Full Text Available Abstract Background Diets rich in omega-3 fatty acids and low in saturated fat were found beneficially associated with blood lipids and cardio-vascular health. Lean reindeer meet and local cold water white-fish species high in omega-3 are among the main sources of nutrients in the rural area of the Nenets Autonomous Okrug (NAO in Russia and are not normally consumed by the urban population from the same region. The aims of the study were firstly, to compare serum lipid profiles of residents of urban (Arkhangelsk city and rural (NAO regions of Arkhangelsk County, and secondly, to investigate the effects of fish consumption on the predictor of cardiovascular events apolipoprotein (Apo B/ApoA-I ratio in these populations. Methods A cross-sectional study conducted in Arkhangelsk County, Russia. Sample size of 249 adults: 132 subjects from Arkhangelsk city, aged 21–70 and 117 subject (87% Ethnic Nenets from NAO, aged 18–69. Results We observed more favorable lipid levels in NAO compared to Arkhangelsk participants. Age-adjusted geometric means of ApoB/ApoA-I ratio were 1.02 and 0.98 in men and women from Arkhangelsk; 0.84 and 0.91 in men and women from NAO respectively. Age and consumption of animal fat were positively associated with ApoB/ApoA-I ratio in women (pooled samples from Arkhangelsk and NAO. Body mass index and low levels of physical activity were positively associated with ApoB/ApoA-I ratio in men (pooled samples from Arkhangelsk and NAO. Reported oily fish consumption was not significantly correlated with ApoB/ApoA-I ratio. Conclusion The population sample from rural NAO, consisting largely of the indigenous Arctic population Nenets with healthier dietary sources, had a relatively less atherogenic lipid profile compared to the urban Arkhangelsk group. Fish consumption had no effect on apolipoproteins profile.

  3. Apolipoprotein C3 polymorphisms, cognitive function and diabetes in Caribbean origin Hispanics.

    Directory of Open Access Journals (Sweden)

    Caren E Smith

    Full Text Available Apolipoprotein C3 (APOC3 modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3 gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention.We examined whether APOC3 single nucleotide polymorphisms (SNPs m482 (rs2854117 and 3u386 (rs5128 were related to cognitive measures, whether the associations between cognitive differences and genotype were related to metabolic differences, and how diabetes status affected these associations. Study subjects were Hispanics of Caribbean origin (n = 991, aged 45-74 living in the Boston metropolitan area.Cognitive and metabolic measures differed substantially by type II diabetes status. In multivariate regression models, APOC3 m482 AA subjects with diabetes exhibited lower executive function (P = 0.009, Stroop color naming score (P = 0.014 and Stroop color-word score (P = 0.022 compared to AG/GG subjects. APOC3 m482 AA subjects with diabetes exhibited significantly higher glucose (P = 0.032 and total cholesterol (P = 0.028 compared to AG/GG subjects. APOC3 3u386 GC/GG subjects with diabetes exhibited significantly higher triglyceride (P = 0.004, total cholesterol (P = 0.003 and glucose (P = 0.016 compared to CC subjects.In summary, we identified significant associations between APOC3 polymorphisms, impaired cognition and metabolic dysregulation in Caribbean Hispanics with diabetes. Further research investigating these relationships in other populations is warranted.

  4. Apolipoprotein J: A New Predictor and Therapeutic Target in Cardiovascular Disease?

    Directory of Open Access Journals (Sweden)

    Ning Yang

    2015-01-01

    Full Text Available Objective: To review the functional mechanism of apolipoprotein J (apoJ in the process of atherosclerosis and the feasibility of apoJ as a therapeutic endpoint. Data Sources: Relevant articles published in English from 1983 to present were selected from PubMed. The terms of "atherosclerosis, apolipoprotein J, clusterin (CLU, oxidative stress, and inflammation" were used for searching. Study Selection: Articles studying the role of apoJ with atherosclerosis and restenosis after injury were reviewed. Articles focusing on the intrinsic determinants of atherosclerosis were selected. The exclusion criteria of articles were that the studies on immunologic vasculitis. Results: ApoJ, involved in numerous physiological process important for lipid transportation and vascular smooth muscle cell differentiation, including apoptotic cell death, cell-cycle regulation, cell adhesion, tissue remodeling, immune system regulation, and oxidative stress, plays a role in the development of clinical atherosclerosis. In the process of relieving atherosclerosis, apoJ can promote cholesterol and phospholipid export from macrophage-foam cells, and exhibit cytoprotective and anti-inflammatory actions by interacting with lots of known inflammatory proteins which may predict the onset of clinical cardiovascular events and may actually play a causal role in mediating atherosclerotic disease such as C-reactive protein, paraoxonase, and leptin. As known as CLU, apoJ has been identified to play central roles in the process of vascular smooth cells migration, adhesion, and proliferation, which can contribute significantly to restenosis after vascular injury. Conclusions: Intense effort and substantial progress have been made to identify the apoJ that relieves atherosclerosis and vascular restenosis after percutaneous coronary intervention. More work is needed to elucidate the exact mechanisms of and the interrelationship between the actions of apoJ and to successfully achieve

  5. Rapid and safe determination of human apolipoprotein E genotypes by miniaturised SDS-PAGE in non-insulin dependent diabetes mellitus.

    OpenAIRE

    C Clavel; Durlach, A.; Durlach, V; Birembaut, P

    1995-01-01

    AIMS--To present a non-isotopic procedure for the analysis of the different apolipoprotein E genotypes in normal subjects and patients with non-insulin dependent diabetes mellitus. METHODS--Apolipoprotein E genotypes were detected following polymerase chain reaction and miniaturised sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) (PhastSystem Pharmacia). RESULTS--The time taken from extraction of DNA from 6 microliters whole blood to the final result was eight hours. The...

  6. Carotid intima-media thickness and apolipoproteins in patients of ischemic stroke in a rural hospital setting in central India: A cross-sectional study

    OpenAIRE

    Jyoti Jain; Tejal Lathia; Om Prakash Gupta; Vishakha Jain

    2012-01-01

    Context: Carotid intima-media thickness (CIMT) and apolipoproteins have been found as a risk factor for ischemic stroke . Objective: The objective was to study the carotid intima-media thickness, apolipoproteins, and their relation in patients of ischemic stroke in central rural India. Settings and Design: A cross-sectional study was performed in a rural hospital in central India. Materials and Methods: In all patients of ischemic stroke proven by computerized tomography (CT), CIMT, apolipopr...

  7. Appreciation of concentration of lipoproteins and apolipoproteins in serum of male rats under the influence of diet change composition and its supplementation with group B vitamins

    OpenAIRE

    Zuzanna Goluch-Koniuszy; Aldona Wierzbicka

    2011-01-01

      Background. This study was aimed at exploring, on animal model, how the diet changes, which results in exceeding 5 times the amount of deficit of group B vitamins after diet change, which up to a certain extent imitates supplementation method in people, influences the concentration of apolipoprotein A-I and apolipoprotein B – the components of lipoprotein HDL-C and LDL-C. Material and methods. The research was conducted on 24 WISTAR male rats, aged ca 5 mo...

  8. Stability Scores: Measuring Coalitional Stability

    OpenAIRE

    Feldman, Michal; Meir, Reshef; Tennenholtz, Moshe

    2011-01-01

    We introduce a measure for the level of stability against coalitional deviations, called \\emph{stability scores}, which generalizes widely used notions of stability in non-cooperative games. We use the proposed measure to compare various Nash equilibria in congestion games, and to quantify the effect of game parameters on coalitional stability. For our main results, we apply stability scores to analyze and compare the Generalized Second Price (GSP) and Vickrey-Clarke-Groves (VCG) ad auctions....

  9. Förster resonance energy transfer measurements are consistent with a helical bundle model for lipid-free apolipoprotein A-I.

    Science.gov (United States)

    Brouillette, Christie G; Dong, Wen-Ji; Yang, Zhengrong W; Ray, Marjorie J; Protasevich, Irina I; Cheung, Herbert C; Engler, Jeffrey A

    2005-12-20

    Apolipoprotein (apo) A-I mutants were constructed for FRET studies to distinguish between two possible lipid-free conformers, a globular helix bundle and an elongated helical hairpin. Mutants containing a single Trp at position 50 were prepared by replacing Trps at positions 8, 72, and 108 with Phe (W@50). Two mutants were constructed from W@50 by incorporating Cys at Arg83 (W@50R83C) or Arg173 (W@50R173C) for attachment of the fluorescent probe AEDANS. Secondary structure of the mutants is very similar to wild type (wt) apo A-I, and fluorescence emission indicates that W50 is protected from solvent. Thermal stabilities of the AEDANS-labeled mutants are also similar to wt. These results indicate that no discernible changes occur in structure or stability as a result of mutations or labeling. The FRET data from W@50 to AEDANS are well-represented by a single distance distribution function with a distance of approximately 22 A for W@50R83C and approximately 19 A for W@50R173C. These distances are consistent with theoretical values calculated from a helical bundle model but not from a helical hairpin. A probability distance distribution function yields significantly small half-width values of 5.6 and 3.7 A, respectively, suggesting low conformational dynamics in both mutants. Differential scanning calorimetry (DSC) was performed on wt and a C-terminal deletion mutant, Delta(187-243), to obtain information on domain architecture. Contrary to expectations, both proteins unfold cooperatively. The results are consistent with the presence of a single folded domain within residues 1-186. These results support the presence of a discrete globular bundle conformation for lipid-free apo A-I. PMID:16342934

  10. Apolipoprotein AIF gene variant S347 is associated with increased risk of coronary heart disease and lower apolipoprotein AIV plasma concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Wai-man R.; Hawe, Emma; Li, Lai K.; Miller, George J.; Nicaud, Viviane; Pennacchio, Len A.; Humphries, Steve E.; Talmud, Philippa J.

    2003-01-30

    The impact of common variants in the apolipoprotein gene cluster (APOC3-A4-A5) on prospective CHD risk was examined in healthy UK men. Of the 2808 men followed over nine years, 187 had a clinically defined CHD event. Examination of 9 single nucleotide polymorphisms (SNPs) in this group revealed that homozygotes for APOA4 S347 had significantly increased risk of CHD [Hazard ratio (HR) of 2.07 (95%CI 1.04-4.12)] while men homozygous for APOC3 1100T were protected (HR 0.28 (95%CI 0.09-0.87)). In stepwise multiple regression analysis, after entering all the variants and adjusting for established risk factors APOA4 T347S alone remained in the model. Using nine-SNP haplotype analysis, highest risk-estimate haplotypes carried APOA4 S347 and rare alleles of the two flanking intergenic markers. The protective effect of APOC31100T could be explained by negative linkage disequilibrium with these alleles. To determine the association of APOA4 T347S with apoAIVlevels, the relationship was examined in over 1600 healthy young European men and women. S347 homozygotes had significantly lower apoAIV plasma levels (13.48 + 0.6mg/dl) compared to carriers of the T347 allele (14.85 + 0.12 mg/dl) (p=0.025). These results demonstrate that genetic variation in and around APOA4, independent of effects of TG, is associated with risk of CHD and apoAIV levels, supporting an anti-atherogenic role for apoAIV.

  11. Expression of the very low-density lipoprotein receptor (VLDL-r), an apolipoprotein-E receptor, in the central nervous system and in Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Christie, R.H.; Chung, Haeyong; Rebeck, G.W.; Hyman, B.T. [Massachusetts General Hospital, Boston, MA (United States)] [and others

    1996-04-01

    The very low density lipoprotein receptor (VLDL-r) is a cell-surface molecule specialized for the internalization of multiple diverse ligands, including apolipoprotein E (apoE)-containing lipoprotein particles, via clathrin-coated pits. Its structure is similar to the low-density lipoprotein receptor (LDL-r), although the two have substantially different systemic distributions and regulatory pathways. The present work examines the distribution of VLDL-r in the central nervous system (CNS) and in relation to senile plaques in Alzheimer disease (AD). VLDL-r is present on resting and activated microglia, particularly those associated with senile plaques (SPs). VLDL-r immunoreactivity is also found in cortical neurons. Two exons of VLDL-r mRNA are differentially spliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycosylation domain near the transmembrane portion of the molecule. The other set of splice forms appears to be brain-specific, and is responsible for the presence or absence of one of the cysteine-rich repeat regions in the binding region of the molecule. Ratios of the receptor variants generated from these splice forms do not differ substantially across different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A{beta} complexes in the brain. Further characterization of apoE receptors in Alzheimer brain may help lay the groundwork for understanding the role of apoE in the CNS and in the pathophysiology of AD. 43 refs., 5 figs.

  12. Ideal Stabilization

    CERN Document Server

    Nesterenko, Mikhail

    2009-01-01

    We define and explore the concept of ideal stabilization. The program is ideally stabilizing if its every state is legitimate. Ideal stabilization allows the specification designer to prescribe with arbitrary degree of precision not only the fault-free program behavior but also its recovery operation. Specifications may or may not mention all possible states. We identify approaches to designing ideal stabilization to both kinds of specifications. For the first kind, we state the necessary condition for an ideally stabilizing solution. On the basis of this condition we prove that there is no ideally stabilizing solution to the leader election problem. We illustrate the utility of the concept by providing examples of well-known programs and proving them ideally stabilizing. Specifically, we prove ideal stabilization of the conflict manager, the alternator, the propagation of information with feedback and the alternating bit protocol.

  13. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Langsted, A.; Freiberg, J.J.; Nordestgaard, Børge

    2008-01-01

    BACKGROUND: Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events. METHODS AND RESULTS: We cross-sectionally studied 33 391 individuals 20 to 95...... HDL cholesterol, and ratio of apolipoprotein B to apolipoprotein A1 did not change in response to normal food intake. The maximum changes after normal food and fluid intake from fasting levels were -0.2 mmol/L for total cholesterol, -0.2 mmol/L for low-density lipoprotein cholesterol, -0.1 mmol/L for...... years of age from the Copenhagen General Population Study. We also studied 9319 individuals 20 to 93 years of age from the Copenhagen City Heart Study, 1166 of whom developed cardiovascular events during 14 years of follow-up. Compared with fasting levels, total cholesterol, low-density lipoprotein...

  14. High-temperature redistribution of cation vacancies and irreversible magnetic transitions in the Fe1−xS nanodisks observed by the Mössbauer spectroscopy and magnetic measurements

    International Nuclear Information System (INIS)

    The hexagonal pyrrhotite Fe1−xS nanodisks with the NiAs-type structure were synthesized by thermal decomposition of ferrous chloride and thiourea in oleylamine. The Mössbauer spectroscopy and magnetic measurements data indicate that a mixture of antiferromagnetic (AFM) and ferrimagnetic (FRM) phases with the NC (N ≥ 3) and 2C-type superstructures is present in the Fe1−xS compound at temperatures between 80 K and Néel temperature TN. At T 370 K, a redistribution of iron vacancies takes place, and the vacancy ordering transforms from the NC (N ≥ 3) to 2C-type which essentially increases the magnetization with maximum value at 470 K. Heating the sample above the Néel temperature 565 K leads to a random distribution of vacancies, and this state is quenched upon subsequent cooling of the sample to 300 K. This gives rise to a pure AFM structure with a zero magnetic moment due to a total compensation of the moments in neighboring iron layers. Thus, the high-temperature redistribution of cation vacancies leads to irreversible magnetic transformations in the Fe1−xS nanoparticles.

  15. TO901317 regulating apolipoprotein M expression mediates via the farnesoid X receptor pathway in Caco-2 cells

    OpenAIRE

    Berggren-Söderlund Maria; Shi Yuanping; Wei Jiang; Wang Zongchun; Luo Guanghua; Zhang Xiaoying; Di Dongmei; Zhu Chunhua; Nilsson-Ehle Peter; Xu Ning

    2011-01-01

    Abstract Background Apolipoprotein M (apoM) may have potential antiatherosclerotic properties. It has been reported that apoM expression could be regulated by many intracellar and extracellar factors. In the present study we further investigated regulation of apoM expression in Caco-2 cells stimulated by a liver X receptor (LXR) agonist, TO901317. Materials and methods Caco-2 cells were cultured in the presence of either TO901317, farnesoid X receptor (FXR) antagonist guggulsterone or TO90131...

  16. The influence of the polymorphism in apolipoprotein B codon 2488 on insulin and lipid levels in a Danish twin population

    DEFF Research Database (Denmark)

    Bentzen, J; Poulsen, P; Vaag, A; Beck-Nielsen, H; Fenger, M

    2002-01-01

    parameters associated with the insulin resistance syndrome in Danish twins. METHODS: The effect of the polymorphism on lipid, glucose and insulin measures was studied in 548 same sex twins aged 55-74 years. RESULTS: The codon 2488 polymorphism influenced fasting triglyceride levels, as well as insulin, as....... As the polymorphism is silent, these effects must be mediated through linkage to other polymorphisms in apolipoprotein B or other genes on chromosome 2....

  17. Effects of Bread with Nigella Sativa on Lipid Profiles, Apolipoproteins and Inflammatory Factor in Metabolic Syndrome Patients.

    Science.gov (United States)

    Mohtashami, Alireaz; Mahaki, Behzad; Azadbakht, Leila; Entezari, Mohammad Hasan

    2016-04-01

    Nigella sativa (N.sativa) has been used in traditional medicine and many studies have been performed in different communities in order to reveal the effects of it on medical disorders and chronic diseases. The aim of this study was to investigate the effects of bread with N. Sativa on lipid profiles, apolipoproteins, and inflammatory factors in metabolic syndrome (MetS) patients. A randomized, double-blind, cross-over and clinical trial was conducted in 51 MetS patients of both sexes with age group of 20-65 years old in Chaloos, north of Iran. Patients were randomly divided in two groups. In phase 1, intervention group (A, n = 27) received daily a bread with N. sativa and wheat bran and control group (B, n = 24) received the same bread without N. sativa for 2 months. After 2 weeks of wash out period, phase 2 was started with switch the intervention between two groups. Measuring of lipid profiles, apolipoproteins and inflammatory factor was performed for all patients before and after two phases. In this study, treatment, sequence and time effects of intervention were evaluated and revealed that consumption of bread with N. sativa has no significant treatment and time effects on triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein (APO)-A, APO-B and high-sensitivity C-reactive protein (p > 0.05). Sequence effect was significant on CHOL, LDL, APO-A, and APO-B (p 0.05). Consumption of bread with N. sativa has no a significant effect on lipid profiles, apolipoproteins and inflammatory factor in MetS patients. PMID:27152298

  18. Biological Monitoring of Hexavalent Chromium and Serum Levels of the Senescence Biomarker Apolipoprotein J/Clusterin in Welders

    OpenAIRE

    Vassilios Makropoulos; Gonos, Efstathios S.; Magda Lourda; Trougakos, Ioannis P.; Xenophon Cominos; Alexopoulos, Evangelos C.

    2008-01-01

    Welding fumes contain metals and other toxic substances known or strongly suspected to be related with oxidative stress and premature cellular senescence. Apolipoprotein J/Clusterin (ApoJ/CLU) is a glycoprotein that is differentially regulated in various physiological and disease states including ageing and age-related diseases. In vitro data showed that exposure of human diploid fibroblasts to hexavalent chromium (Cr(VI)) resulted in premature senescence and significant upregulation of the A...

  19. Endothelial Dysfunction in the Apolipoprotein E-deficient Mouse: insights into the influence of diet, gender and aging

    OpenAIRE

    Meyrelles Silvana S; Peotta Veronica A; Pereira Thiago MC; Vasquez Elisardo C

    2011-01-01

    Abstract Since the early 1990s, several strains of genetically modified mice have been developed as models for experimental atherosclerosis. Among the available models, the apolipoprotein E-deficient (apoE-/-) mouse is of particular relevance because of its propensity to spontaneously develop hypercholesterolemia and atherosclerotic lesions that are similar to those found in humans, even when the mice are fed a chow diet. The main purpose of this review is to highlight the key achievements th...

  20. The influence of parental history of Alzheimer's disease and apolipoprotein E ε4 on the BOLD signal during recognition memory

    OpenAIRE

    Xu, Guofan; McLaren, Donald G.; Ries, Michele L.; Fitzgerald, Michele E.; Barbara B. Bendlin; Howard A. Rowley; Sager, Mark A.; Atwood, Craig; Asthana, Sanjay; Johnson, Sterling C.

    2008-01-01

    First-degree family history (FH) of sporadic Alzheimer's disease and the apolipoprotein E ε4 allele (APOE4) are risk factors for Alzheimer's disease that may affect brain function prior to onset of clinical symptoms. In this functional MRI (fMRI) study, we used an episodic recognition task that required discrimination of previously viewed (PV) and novel (NV) faces to examine differences in blood oxygen level dependent (BOLD) signal due to risk factors in 74 middle-aged cognitively normal indi...

  1. Effects of Bread with Nigella Sativa on Lipid Profiles, Apolipoproteins and Inflammatory Factor in Metabolic Syndrome Patients

    Science.gov (United States)

    2016-01-01

    Nigella sativa (N.sativa) has been used in traditional medicine and many studies have been performed in different communities in order to reveal the effects of it on medical disorders and chronic diseases. The aim of this study was to investigate the effects of bread with N. Sativa on lipid profiles, apolipoproteins, and inflammatory factors in metabolic syndrome (MetS) patients. A randomized, double-blind, cross-over and clinical trial was conducted in 51 MetS patients of both sexes with age group of 20-65 years old in Chaloos, north of Iran. Patients were randomly divided in two groups. In phase 1, intervention group (A, n = 27) received daily a bread with N. sativa and wheat bran and control group (B, n = 24) received the same bread without N. sativa for 2 months. After 2 weeks of wash out period, phase 2 was started with switch the intervention between two groups. Measuring of lipid profiles, apolipoproteins and inflammatory factor was performed for all patients before and after two phases. In this study, treatment, sequence and time effects of intervention were evaluated and revealed that consumption of bread with N. sativa has no significant treatment and time effects on triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein (APO)-A, APO-B and high-sensitivity C-reactive protein (p > 0.05). Sequence effect was significant on CHOL, LDL, APO-A, and APO-B (p 0.05). Consumption of bread with N. sativa has no a significant effect on lipid profiles, apolipoproteins and inflammatory factor in MetS patients. PMID:27152298

  2. Vitamin D Deficiency and Exogenous Vitamin D Excess Similarly Increase Diffuse Atherosclerotic Calcification in Apolipoprotein E Knockout Mice

    OpenAIRE

    Ellam, Timothy; Hameed, Abdul; ul Haque, Risat; Muthana, Munitta; Wilkie, Martin; Francis, Sheila E.; Chico, Timothy J. A.

    2014-01-01

    Background Observational data associate lower levels of serum vitamin D with coronary artery calcification, cardiovascular events and mortality. However, there is little interventional evidence demonstrating that moderate vitamin D deficiency plays a causative role in cardiovascular disease. This study examined the cardiovascular effects of dietary vitamin D deficiency and of vitamin D receptor agonist (paricalcitol) administration in apolipoprotein E knockout mice. Methods Mice were fed athe...

  3. Role of apolipoprotein E4 in protecting children against early childhood diarrhea outcomes and implications for later development

    OpenAIRE

    Oriá, Reinaldo B.; Patrick, Peter D.; Blackman, James A.; Lima, Aldo A.M.; Guerrant, Richard L.

    2006-01-01

    Our group and others have reported a series of studies showing that heavy burdens of diarrheal diseases in the formative first two years of life in children in urban shantytowns have profound consequences of impaired physical and cognitive development lasting into later childhood and schooling. Based on these previous studies showing that apolipoprotein E4 (APOE4) is relatively common in favela children, we review recent data suggesting a protective role for the APOE4 allele in the cognitive ...

  4. Frequency of the apolipoprotein E epsilon 4 allele in a case-control study of early onset Parkinson's disease.

    OpenAIRE

    Whitehead, A S; Bertrandy, S.; Finnan, F; Butler, A; G. D. Smith(Edinburgh University); Ben-Shlomo, Y.

    1996-01-01

    OBJECTIVES: It has been suggested that Parkinson's disease and Alzheimer's disease may share a common or at least overlapping aetiology. The prevalence of dementia among cases of Parkinson's disease is known to be greater than expected in the general population. The frequency of the apolipoprotein epsilon 4 allele in a large case-control study of early onset Parkinson's disease has been examined. METHODS: 215 patients and 212 population based controls were recruited from the Republic of Irela...

  5. Apolipoprotein E4 Genotype and Depressive Symptoms as Risk Factors for Dementia in an Older Korean Population

    OpenAIRE

    Kim, Jae-Min; Kim, Seon-Young; Bae, Kyung-Yeol; Kim, Sung-Wan; Shin, Il-Seon; Yang, Su-Jin; Song, Young-Heon; Yoon, Jin-Sang

    2010-01-01

    Objective Growing evidence suggests the separate associations of apolipoprotein E e4 allele (apo E4) and depression with incident dementia. This study investigated the separate and combined effects of apo E4 and depression on the incidence of dementia in both men and women. Methods Of 625 elderly without dementia at baseline, 518 (83%) were followed over a 2.4-year period and were assessed clinically for incident dementia. The apo E polymorphism was ascertained, and depression was identified ...

  6. Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E

    Science.gov (United States)

    Rute Neves, Ana; Fontes Queiroz, Joana; Weksler, Babette; Romero, Ignacio A.; Couraud, Pierre-Olivier; Reis, Salette

    2015-12-01

    Nanotechnology can be an important tool to improve the permeability of some drugs for the blood-brain barrier. In this work we created a new system to enter the brain by functionalizing solid lipid nanoparticles with apolipoprotein E, aiming to enhance their binding to low-density lipoprotein receptors on the blood-brain barrier endothelial cells. Solid lipid nanoparticles were successfully functionalized with apolipoprotein E using two distinct strategies that took advantage of the strong interaction between biotin and avidin. Transmission electron microscopy images revealed spherical nanoparticles, and dynamic light scattering gave a Z-average under 200 nm, a polydispersity index below 0.2, and a zeta potential between -10 mV and -15 mV. The functionalization of solid lipid nanoparticles with apolipoprotein E was demonstrated by infrared spectroscopy and fluorimetric assays. In vitro cytotoxic effects were evaluated by MTT and LDH assays in the human cerebral microvascular endothelial cells (hCMEC/D3) cell line, a human blood-brain barrier model, and revealed no toxicity up to 1.5 mg ml-1 over 4 h of incubation. The brain permeability was evaluated in transwell devices with hCMEC/D3 monolayers, and a 1.5-fold increment in barrier transit was verified for functionalized nanoparticles when compared with non-functionalized ones. The results suggested that these novel apolipoprotein E-functionalized nanoparticles resulted in dynamic stable systems capable of being used for an improved and specialized brain delivery of drugs through the blood-brain barrier.

  7. Estimation of plasma apolipoprotein B concentration using routinely measured lipid biochemical tests in apparently healthy Asian adults

    Directory of Open Access Journals (Sweden)

    Cho Dong-Sik

    2012-05-01

    Full Text Available Abstract Background Increased low-density lipoprotein cholesterol (LDL concentration is associated with increased risk of coronary heart disease (CHD but a substantial risk of cardiovascular disease often remains after LDL concentrations have been treated to target. Apolipoprotein B (apo B is the major apolipoprotein contained within atherogenic lipoproteins such as LDL, and apo B is a more reliable indicator of cardiovascular risk than LDL concentration. Aim and methods Our aim was to develop a formula for calculating apo B using lipid biochemistry measurements that are commonly available in clinical practice. We examined the clinical and laboratory data from 73,047 Koreans who underwent a medical health check that included apolipoprotein B concentration. The study sample was randomly divided into a training set for prediction model building and a validation set of equal size. Multivariable linear regression analysis was used to develop a prediction model equation for estimating apo B and to validate the developed model. Results The best results for estimating apo B were derived from an equation utilising LDL and triglyceride (TG concentrations [ApoB = −33.12 + 0.675*LDL + 11.95*ln(tg]. This equation predicted the apo B result with a concordance correlation coefficient (CCC and 95%CIs = 0.936 (0.935,0.937. Conclusion Our equation for predicting apo B concentrations from routine analytical lipid biochemistry provides a simple method for obtaining precise information about an important cardiovascular risk marker.

  8. Apolipoprotein A-I localization and dipalmitoylphosphatidylcholine dynamics in reconstituted high density lipoproteins.

    Science.gov (United States)

    Dergunov, A D; Dobretsov, G E

    2000-02-01

    The structure and molecular dynamics of recombinant high density lipoproteins (rHDL) were studied by non-radiative energy transfer (NRET), fluorescence anisotropy and intensity measurements. The rHDL particles contained human plasma apolipoprotein (apo) A-I and dipalmitoylphosphatidylcholine (DPPC). Fluorescent cis- and trans-parinaric acids were used both as probes of molecular motion in the particle lipid phase and as acceptors in the Forster's energy transfer from apo A-I tryptophan residues to determine particle dimensions, apolipoprotein localization and lipid dynamics. The probes are sensitive to thermal wobbling (macromobility) and conformational deformations (micromobility) of phospholipid acyl chains. The experimental data fitted to various models of the particle structure are compatible with the following: (a) at T DPPC molecules in rHDL were more rapid due to a significant disorder of the boundary lipid molecules close to the apo A-I molecule. This disorder led to the increase of the specific surface area per one lipid molecule, S(o). The lipid phase can be divided into three regions: (i) zone I of the most tightly packed lipid (0-1.7 nm from the disc axis) with a S(o) value small as 0.5 nm2; (ii) intermediate zone II (from 1.7 to 4.0 nm); and (iii) boundary lipid zone III (4-5 nm) of significantly disordered lipid with a S(o) value large as 0.65 nm2. (b) at T> Tt the S(o) heterogeneity disappeared, the radius of the lipid phase did not increase significantly, not exceeding 5.2-5.4 nm, but protein-induced immobilization of lipid molecules which affected about half or more of the total lipid, became remarkable. The overall effect was the suppression of the transition amplitude in rHDL compared to liposomes. The structural inhomogeneity might underlie the function of the native plasma HDL as the key component of the transport and metabolism of plasma lipids. PMID:10669308

  9. Enhanced Diabetes Susceptibility in Community Dwelling Han Elders Carrying the Apolipoprotein E 3/3 Genotype.

    Directory of Open Access Journals (Sweden)

    Chun-Xia Ban

    Full Text Available Despite Apolipoprotein E (ApoE being one of the main apolipoproteins in the blood, the association between its genotype and the high cholesterol or blood glucose levels commonly seen in clinical practice is inconclusive. Such research is also lacking in the Han population. The aim of this study was to investigate the association between APOE genotype, diabetes, and plasma glucose and lipid levels. We included 243 community-dwelling elderly residents in this study. Participant APOE genotypes were assessed and were simultaneously tested for weight, height, blood glucose, triglycerides, cholesterol, and high- and low-density lipoprotein. In addition, gender, age, years of education, cognitive function, and medical history was recorded. Subjects were divided into 3 groups based on APOE genotype: APOE ε2 group (ε2/ε2 and ε2/ε3, APOE ε3 group (ε3/ε3, and APOE ε4 group (ε2/ε4, ε3/ε4 and ε4/ε4. Comparisons between groups were conducted for the incidence of diabetes, high blood pressure, and dementia, as well as for differences in body-mass index, fasting plasma glucose, and blood lipids. The APOE ε3/ε3 genotype exhibited the highest frequency (70.4% among the subjects. Participants in the APOE ε3 group demonstrated significantly higher levels of fasting plasma glucose than those in the APOE ε2 and APOE ε4 groups (P<0.05. The APOE ε3 group had slightly higher abnormal fasting plasma glucose values than did the APOE ε2 group (P = 0.065. Furthermore, the APOE3 genotype was significantly correlated with both fasting plasma glucose level and glucose abnormality (P< 0.05 and trended toward statistically significant correlation with diabetes (P = 0.082. The correlation between APOE2 and low low-density lipoprotein levels also approached statistical significance (P = 0.052. Thus, elderly community dwelling residents of Han ethnicity carrying the APOE ε3/ε3 genotype might have higher plasma glucose levels and a higher occurrence of

  10. ApolipoproteinE ε4 allelic variant, cognitive decline and psychosis in Alzheimer disease: a review of the literature and suggestions for upcoming studies

    Directory of Open Access Journals (Sweden)

    Ilaria Spoletini

    2006-06-01

    Full Text Available Apolipoprotein E (ApoE ε4 allele represents a well known vascular risk factor for developing Alzheimer disease (AD and differences in ApoE genotypes may explain a part of the variability in AD phenotypes. In fact, ApoE ε4 allele possession seems to be associated with a more precocious age of onset, greater episodic memory impairment, and psychotic symptoms. The first question we discuss regards the role of ApoE ε4 on cognitive progression of AD. In fact, while a general agreement exists about the role played by ApoE ε4 on the precocious onset of AD, cognitive decline has been differently associated with ApoE ε4 allele possession in AD patients in a continuum of faster decline, no effect, and slower decline. An attemptable interpretation is that the biological processes leading to the onset of AD are different from those involved in determining its clinical course. The second question regards the possible relationship between the presence of the degenerative pathological hallmarks of the disease in specific cerebral areas and different cognitive or behavioural symptoms. In fact, there is evidence that degenerative pathology in hippocampal formation and frontal cortex reflects the progression of cognitive deficits in brain aging and AD and that hypometabolism in right frontal lobe and greater frontal neuropsychological deficits occur in AD patients with psychosis in comparison to those without. The third question regards, specifically, the relationship between ApoE ε4 variant and behavioural symptoms. In fact, there is evidence supporting the link between being carriers of ApoE ε4 allele and severity of delusions, mostly at the early stage of the illness. In an interpretative challenge, we suggest that the link between being carriers of ApoE ε4 allele and suffering from delusions in AD may be explained by frontal lobe dysfunctions. Finally, we hypothesize that the most precocious onset of AD illness, described in carriers of ApoE ε4

  11. Expression of the human apolipoprotein E gene suppresses steroidogenesis in mouse Y1 adrenal cells

    International Nuclear Information System (INIS)

    The lipid transport protein, apolipoprotein E (apoE), is expressed in many peripheral tissues in vivo including the adrenal gland and testes. To investigate the role of apoE in adrenal cholesterol homeostasis, the authors have expressed a human apoE genomic clone in the Y1 mouse adrenocortical cell line. Y1 cells do not express endogenous apoE mRNA or protein. Expression of apoE in Y1 cells resulted in a dramatic decrease in basal steroidogenesis; secretion of fluorogenic steroid was reduced 7- to >100-fold relative to Y1 parent cells. Addition of 5-cholesten-3β,25-idol failed to overcome the suppression of steroidogenesis in these cells. Cholesterol esterification under basal conditions, as measured by the production of cholesteryl [14C]oleate, was similar in the Y1 parent and the apoE-transfected cell lines. Upon incubation with adrenocorticotropin or dibutyryl cAMP, production of cholesteryl [14C]oleate decreased 5-fold in the Y1 parent cells but was unchanged in the apoE-transfected cell lines. These results suggest that apoE may be an important modulator of cholesterol utilization and steroidogenesis in adrenal cells

  12. Association of apolipoprotein E polymorphism with plasma lipids and Alzheimer's disease in a Southern Brazilian population

    Directory of Open Access Journals (Sweden)

    de-Andrade F.M.

    2000-01-01

    Full Text Available Apolipoprotein E (protein: apo E; gene: APOE plays an important role in the multifactorial etiology of both Alzheimer's disease (AD and lipid level concentrations. The polymerase chain reaction (PCR was used to investigate the APOE gene polymorphism in 446 unrelated Caucasians, among them 23 AD patients, and 100 Afro-Brazilians living in Porto Alegre, Brazil. The frequencies of the APOE*2, APOE*3 and APOE*4 alleles were 0.075, 0.810 and 0.115 in Caucasians and 0.075, 0.700 and 0.225 in Afro-Brazilians, respectively (c2 = 8.72, P = 0.013. A highly significant association was observed between the APOE*4 allele and AD in this population-based sample. The APOE*4 frequency in AD patients (39% was about four times higher than in the general Caucasian population (11.5%. The influence of each of the three common APOE alleles on lipid traits was evaluated by the use of the average excess statistic. The E*2 allele is associated with lower levels of triglycerides and of total and non-HDL cholesterol in both men and women. Conversely, the E*4 allele is associated with higher levels of these traits in women only. The effect of APOE alleles was of greater magnitude in women.

  13. Apolipoprotein E Gene Polymorphisms in Saudi Patients with Systemic Lupus Erythematosus

    Science.gov (United States)

    Al-Rayes, Hannan; Huraib, Ghaleb; Julkhuf, Saeed; Arfin, Misbahul; Tariq, Mohammad; Al-Asmari, Abdulrahman

    2016-01-01

    Apolipoprotein E (APOE) is a glycosylated protein with multiple biological properties. APOE gene polymorphism plays a central role in lipid metabolism and has recently been suggested to regulate inflammation. Our objective is to evaluate whether APOE polymorphism affects susceptibility to SLE. APOE genotyping was performed using ApoE StripAssay™ kit. Results indicated significantly higher frequencies of allele ε4 and genotype ε3/ε4 and lower frequencies of allele ε3 and genotype ε3/ε3 in SLE patients than controls. APOE ε2 allele was found in three patients, whereas it was absent in controls. The frequencies of allele ε4 and genotype ε3/ε4 were significantly higher in SLE patients with renal involvement and those of alleles ε2, ε4 and genotypes ε2/ε3, ε3/ε4 were higher in patients with neuropsychiatric symptoms. It is concluded that APOE allele ε4 is associated with susceptibility risk/clinical manifestations of SLE and ε2 may increase its severity while ε3 is protective for SLE in Saudis. PMID:27257397

  14. Apolipoprotein E-specific innate immune response in astrocytes from targeted replacement mice

    Directory of Open Access Journals (Sweden)

    Montine Thomas J

    2006-04-01

    Full Text Available Abstract Background Inheritance of the three different alleles of the human apolipoprotein (apo E gene (APOE are associated with varying risk or clinical outcome from a variety of neurologic diseases. ApoE isoform-specific modulation of several pathogenic processes, in addition to amyloid β metabolism in Alzheimer's disease, have been proposed: one of these is innate immune response by glia. Previously we have shown that primary microglia cultures from targeted replacement (TR APOE mice have apoE isoform-dependent innate immune activation and paracrine damage to neurons that is greatest with TR by the ε4 allele (TR APOE4 and that derives from p38 mitogen-activated protein kinase (p38MAPK activity. Methods Primary cultures of TR APOE2, TR APOE3 and TR APOE4 astrocytes were stimulated with lipopolysaccharide (LPS. ApoE secretion, cytokine production, and nuclear factor-kappa B (NF-κB subunit activity were measured and compared. Results Here we showed that activation of primary astrocytes from TR APOE mice with LPS led to TR APOE-dependent differences in cytokine secretion that were greatest in TR APOE2 and that were associated with differences in NF-κB subunit activity. Conclusion Our results suggest that LPS activation of innate immune response in TR APOE glia results in opposing outcomes from microglia and astrocytes as a result of TR APOE-dependent activation of p38MAPK or NF-κB signaling in these two cell types.

  15. Apolipoprotein E isotype-dependent modulation of microRNA-146a in plasma and brain.

    Science.gov (United States)

    Teter, Bruce; LaDu, Mary Jo; Sullivan, Patrick M; Frautschy, Sally A; Cole, Greg M

    2016-08-01

    The Apolipoprotein E (ApoE) isotype ApoE4 is a prevalent genetic risk factor for Alzheimer's disease (AD) that can modulate systemic and central inflammation, independent of amyloid accumulation. Although disruption of innate immune toll receptor signaling is modulated by ApoE and observed in AD, ApoE isotype-specific effects remain poorly understood. Therefore, we examined the effect of the ApoE isotype on the brain levels of major regulators of TLR signaling including miR146a, a microRNA enriched in the brain. We used 6-month-old ApoE3 or ApoE4 targeted replacement mice with and without mutant familial AD transgenes. ApoE4 reduced the levels of miR146a compared with ApoE3, both in the brain (29%; Pimmune stimuli (including Aβ) in ApoE4 carriers. Thus, ApoE4 causes early dysregulation of a central controller of the innate immune system both centrally and systemically. This defect persists with familial AD pathology and may be relevant to ApoE4 AD risk. PMID:27281274

  16. Mechanism of lipid lowering in mice expressing human apolipoprotein A5

    Energy Technology Data Exchange (ETDEWEB)

    Fruchart-Najib, Jamila; Bauge, Eric; Niculescu, Loredan-Stefan; Pham, Tatiana; Thomas, Benoit; Rommens, Corinne; Majd, Zouher; Brewer, Bryan; Rubin, Edward M.; Pennacchio, Len A.; Fruchart, Jean-Charles

    2004-01-15

    Recently, we reported that apoAV plays key role in triglycerides lowering. Here, we attempted to determine the mechanism underlying this hypotriglyceridemic effect. We showed that triglyceride turnover is faster in hAPOA5 transgenic compared to wild type mice. Moreover, both apoB and apoCIII are decreased and LPL activity is increased in postheparin plasma of hAPOA5 transgenic mice. These data suggest a decrease in size and number of VLDL. To further investigate the mechanism of hAPOA5 in hyperlipidemic background, we intercrossed hAPOA5 and hAPOC3 transgenic mice. The effect resulted in a marked decreased of VLDL triglyceride, cholesterol, apolipoproteins B and CIII. In postprandial state, the triglyceride response is abolished in hAPOA5 transgenic mice. We demonstrated that in response to the fat load in hAPOA5XhAPOC3 mice, apoAV shifted from HDL to VLDL, probably to limit the elevation of triglycerides. In vitro, apoAV activates lipoprotein lipase. However, apoAV does not interact with LPL but interacts physically with apoCIII. This interaction does not seem to displace apoCIII from VLDL but may induce conformational change in apoCIII and consequently change in its function leading the activation of lipoprotein lipase.

  17. Screening for the familial defective apolipoprotein B-100 R3500W by mutagenic primers PCR

    Institute of Scientific and Technical Information of China (English)

    冯纪安; 冯铮

    2002-01-01

    Objective A method combining the mutagenic primers PCR and restriction enzyme digestion was designed to facilitate the detection of gene mutation in familial defective apolipoprotein B-1O0 R3500W. Methods A pair of primer was designed and a mismatch nucleotide was introduced in its upstream primer. A segment of target DNA including the possibly mutated nucleotide was amplified by PCR and the products were digested by restriction enzyme Nco 1. To overcome the potential false negative results due to improper digestion conditions, a segment of DNA with Ncol cut size was added as reference.Results The target sequence was successfully amplified by PCR, producing a 144 bp DNA fragment as expected. When incubated with Ncol, the enzyme could digest the DNA, producing a 114 bp segment,only if it was amplified from the mutated gene, but not from the normal allele. This difference in length of DNA could be separated by electrophoresis on a 2 %agarose gel. Thus we successfully detected two carriers of heterozygous FDB R3500W in 162 hypercholesterolemic patients. Conclusions Mutagenic primers PCR can be used to detect the gene mutation of apo B-100 R3500W, two cases were detected among 162patients with hypercholesterolemia. It suggests that this mutation is not rare in mainland China.

  18. Correlation between haplotype of apolipoprotein B gene and natural longevity persons in Uygur Nationality

    Institute of Scientific and Technical Information of China (English)

    JIANG WenXi; QIU ChangChun; CHENG ZuHeng; ZHOU WenYu; GU MingLiang; XU Qun; FANG MingWu; NIU WenQuan

    2007-01-01

    This paper investigated the correlation between polymorphisms and haplotypes in the apolipoprotein B (apoB) gene (SP-I/D, XbaI-RFLP, VNTR) and natural longevity persons among the Uygur people in Xinjiang. For this purpose, 191 healthy Uygur individuals aged above 90 from Hetian area of Xinjiang were recruited, and another 53 persons aged 65-70 from the same nationality, the same region and with the same gender ratio, served as the control group. Genotyping was performed by PCR-SSP, PCR-RFLP and PCR-sequencing methods. Logistic regression analyses revealed that the frequencies of X+X+ genotype, M and L alleles and the genetypes composed of M and L were significantly higher in the longevity group than in the control group. In haplotype analyses, we found that, in the long-lived people, the frequency of haplotypes composed of the X+ and M alleles was significantly higher whereas the frequency of haplotypes composed of the X- and S alleles was significantly lower (both P<0.05) I than those of their controls. These results indicated that the S allele, SS genotype and X+-S, D-S, D-X+-S haplotypes were the possible adverse factors, whereas the M, L alleles, X+X+, MM, ML, LL genotypes and I-X+-M, X+-M haplotypes were the possibe protective factors for the naturally long-lived Uygur people in China.

  19. Correlation between haplotype of apolipoprotein B gene and natural longevity persons in Uygur Nationality

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This paper investigated the correlation between polymorphisms and haplotypes in the apolipoprotein B (apoB) gene (SP-I/D, XbaI-RFLP, VNTR) and natural longevity persons among the Uygur people in Xin-jiang. For this purpose, 191 healthy Uygur individuals aged above 90 from Hetian area of Xinjiang were recruited, and another 53 persons aged 65—70 from the same nationality, the same region and with the same gender ratio, served as the control group. Genotyping was performed by PCR-SSP, PCR-RFLP and PCR-sequencing methods. Logistic regression analyses revealed that the frequencies of X+X+ genotype, M and L alleles and the genetypes composed of M and L were significantly higher in the longevity group than in the control group. In haplotype analyses, we found that, in the long-lived people, the frequency of haplotypes composed of the X+ and M alleles was significantly higher whereas the frequency of haplotypes composed of the X- and S alleles was significantly lower (both P<0.05) I than those of their controls. These results indicated that the S allele, SS genotype and X+-S, D-S, D-X+-S haplotypes were the possible adverse factors, whereas the M, L alleles, X+X+, MM, ML, LL genotypes and I-X+-M, X+-M haplotypes were the possibe protective factors for the naturally long-lived Uygur people in China.

  20. Longitudinal Trajectories of Cholesterol from Midlife through Late Life according to Apolipoprotein E Allele Status

    Directory of Open Access Journals (Sweden)

    Brian Downer

    2014-10-01

    Full Text Available Background: Previous research indicates that total cholesterol levels increase with age during young adulthood and middle age and decline with age later in life. This is attributed to changes in diet, body composition, medication use, physical activity, and hormone levels. In the current study we utilized data from the Framingham Heart Study Original Cohort to determine if variations in apolipoprotein E (APOE, a gene involved in regulating cholesterol homeostasis, influence trajectories of total cholesterol, HDL cholesterol, and total: HDL cholesterol ratio from midlife through late life. Methods: Cholesterol trajectories from midlife through late life were modeled using generalized additive mixed models and mixed-effects regression models. Results: APOE e2+ subjects had lower total cholesterol levels, higher HDL cholesterol levels, and lower total: HDL cholesterol ratios from midlife to late life compared to APOE e3 and APOE e4+ subjects. Statistically significant differences in life span cholesterol trajectories according to gender and use of cholesterol-lowering medications were also detected. Conclusion: The findings from this research provide evidence that variations in APOE modify trajectories of serum cholesterol from midlife to late life. In order to efficiently modify cholesterol through the life span, it is important to take into account APOE allele status.

  1. Taurine reduces the secretion of apolipoprotein B100 and lipids in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Nagao Koji

    2008-10-01

    Full Text Available Abstract Background Higher concentrations of serum lipids and apolipoprotein B100 (apoB are major individual risk factors of atherosclerosis and coronary heart disease. Therefore ameliorative effects of food components against the diseases are being paid attention in the affluent countries. The present study was undertaken to investigate the effect of taurine on apoB secretion and lipid metabolism in human liver model HepG2 cells. Results The results demonstrated that an addition of taurine to the culture media reduces triacylglycerol (TG-mass in the cells and the medium. Similarly, cellular cholesterol-mass was decreased. Taurine inhibited the incorporation of [14C] oleate into cellular and medium TG, suggesting the inhibition of TG synthesis. In addition, taurine reduced the synthesis of cellular cholesterol ester and its secretion, suggesting the inhibition of acyl-coenzyme A:cholesterol acyltransferase activity. Furthermore, taurine reduced the secretion of apoB, which is a major protein component of very low-density lipoprotein. Conclusion This is a first report to demonstrate that taurine inhibits the secretion of apoB from HepG2 cells.

  2. Apolipoprotein E in the genetics and epidemiology of Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, J. [Univ. of South Florida, Tampa, FL (United States)

    1995-10-09

    The role of apolipoprotein E (ApoE) alleles and isoforms in the etiology and pathogenesis of Alzheimer`s disease is discussed. The possibility that ApoE itself is not involved in the disease pathogenesis but is merely in genetic disequilibrium with the real locus is discussed and dismissed. The data showing that the {epsilon}4 allele is associated with an increased risk of developing the disease and with an earlier onset age are reviewed. The data showing that, at least in some circumstances, the {epsilon}2 allele is associated with a decrease in the risk of developing the disease, and with a later onset age are also reviewed. Data from the genetic analysis of other disorders are reviewed and presented, and it is suggested that the genetic data support the notion that the role of ApoE in the etiology of the disease directly relates to {beta}-amyloid deposition and plaque formation. This suggestion is in concordance with the most likely mechanism for the role of P-amyloid precursor protein gene mutations as other risk factors for the disease. 68 refs.

  3. Possible role of apolipoprotein A1 in healing and cell death after neuronal injury.

    Science.gov (United States)

    Sengupta, Mohor B; Mukhopadhyay, Debashis

    2016-01-01

    Limited axonal regeneration after traumatic injuries to the CNS presents a challenge in neuroscience. Investigation of CSF from subjects with spinal cord injury (SCI) has found that the lipid catabolism pathway is implicated in the post injury scenario. Sequestration of the CNS by the blood brain barrier ensures a mechanism of cholesterol metabolism and recycling distinct from that in the peripheral tissues. Apolipoprotein A1, the protein component of high density lipoprotein (HDL), is an abundant protein in the mammalian cerebrospinal fluid. Interaction of ApoA1 with its cellular receptor, ABCA1, gives rise to several signaling events, such as the activation of Cdc42 protein leading to actin polymerisation. Emerging evidences suggest that ApoA1 mediates anti-inflammatory effects and conversely, is negatively regulated by inflammatory cytokines. Collating these findings, added to the clinical evidences of using HDL as a therapeutic target for cardio vascular diseases, we hypothesize that ApoA1 could be useful in neurite outgrowth after mechanical injury by 1) mediating polymerisation of actin and 2) restricting inflammatory responses after injury which are deleterious to healing. PMID:27100352

  4. Plasma levels of apolipoprotein E and risk of dementia in the general population

    DEFF Research Database (Denmark)

    Rasmussen, Katrine L; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G; Frikke-Schmidt, Ruth

    2015-01-01

    OBJECTIVE: The apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer disease and dementia. However, it remains unclear whether plasma levels of apoE confer additional risk. We tested this hypothesis. METHODS: Using 75,708 participants from the general population, we tested...... whether low plasma levels of apoE at study enrollment were associated with increased risk of future Alzheimer disease and all dementia, and whether this association was independent of ε2/ε3/ε4 APOE genotype. RESULTS: Multifactorially adjusted hazard ratios (HRs) for Alzheimer disease and all dementia...... increased from the highest to the lowest apoE tertile (p for trends < 1 × 10(-6) ). Multifactorially adjusted HRs for lowest versus highest tertile were 2.68 (95% confidence interval [CI] = 2.04-3.52) and 1.80 (95% CI = 1.52-2.13) for Alzheimer disease and all dementia, respectively. After further...

  5. Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.

    LENUS (Irish Health Repository)

    Trompet, Stella

    2009-12-01

    Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.34, 2.70) and cancer mortality (HR = 2.03, 95% CI: 1.23, 3.34) relative to subjects within the highest third of plasma cholesterol. However, carriers of the ApoE2 genotype (n = 332), who had 9% lower plasma cholesterol levels than carriers of the ApoE4 genotype (n = 635), did not have increased risk of cancer incidence (HR = 0.86, 95% CI: 0.50, 1.47) or cancer mortality (HR = 0.70, 95% CI: 0.30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk.

  6. Mammalian embryonic cerebrospinal fluid proteome has greater apolipoprotein and enzyme pattern complexity than the avian proteome.

    Science.gov (United States)

    Parada, Carolina; Gato, Angel; Bueno, David

    2005-01-01

    During early stages of embryo development, the brain cavity is filled with Embryonic Cerebro-Spinal Fluid, which has an essential role in the survival, proliferation and neurogenesis of the neuroectodermal stem cells. We identified and analyzed the proteome of Embryonic Cerebro-Spinal Fluid from rat embryos (Rattus norvegicus), which includes proteins involved in the regulation of Central Nervous System development. The comparison between mammalian and avian Embryonic Cerebro-Spinal Fluid proteomes reveals great similarity, but also greater complexity in some protein groups. The pattern of apolipoproteins and enzymes in CSF is more complex in the mammals than in birds. This difference may underlie the greater neural complexity and synaptic plasticity found in mammals. Fourteen Embryonic Cerebro-Spinal Fluid gene products were previously identified in adult human Cerebro-Spinal Fluid proteome, and interestingly they are altered in patients with neurodegenerative diseases and/or neurological disorders. Understanding these molecules and the mechanisms they control during embryonic neurogenesis may contribute to our understanding of Central Nervous System development and evolution, and these human diseases. PMID:16335996

  7. Homozygous familial hypobetalipoproteinemia: A Turkish case carrying a missense mutation in apolipoprotein B.

    Science.gov (United States)

    Yilmaz, Berna Seker; Mungan, Neslihan Onenli; Di Leo, Enza; Magnolo, Lucia; Artuso, Lucia; Bernardis, Isabella; Tumgor, Gokhan; Kor, Deniz; Tarugi, Patrizia

    2016-01-15

    The autosomal co-dominant disorder familial hypobetalipoproteinemia (FHBL) may be due to mutations in the APOB gene encoding apolipoprotein B (apoB), the main constituent peptide of chylomicrons, very low and low density lipoproteins. We describe an 11month-old child with failure to thrive, intestinal lipid malabsorption, hepatic steatosis and severe hypobetalipoproteinemia, suggesting the diagnosis of homozygous FHBL, abetalipoproteinemia (ABL) or chylomicron retention disease (CMRD). The analysis of candidate genes showed that patient was homozygous for a variant (c.1594 C>T) in the APOB gene causing arginine to tryptophan conversion at position 505 of mature apoB (Arg505Trp). No mutations were found in a panel of other potential candidate genes for hypobetalipoproteinemia. In vitro studies showed a reduced secretion of mutant apoB-48 with respect to the wild-type apoB-48 in transfected McA-RH7777 cells. The Arg505Trp substitution is located in the βα1 domain of apoB involved in the lipidation of apoB mediated by microsomal triglyceride transfer protein (MTP), the first step in VLDL and chylomicron formation. The patient's condition improved in response to a low fat diet supplemented with fat-soluble vitamins. Homozygosity for a rare missense mutation in the βα1 domain of apoB may be the cause of both severe hypobetalipoproteinemia and intestinal lipid malabsorption. PMID:26612772

  8. Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription

    Directory of Open Access Journals (Sweden)

    Bin Hong

    2012-06-01

    Full Text Available Apolipoprotein A-I (Apo A-I is the principal protein component of high density lipoprotein (HDL, which is generally considered as a potential therapeutic target against atherosclerosis. The understanding of the Apo A-I regulation mechanism has fuelled the development of novel HDL targeted therapeutic approaches. To identify novel agents that can upregulate Apo A-I expression, we performed a cell-based reporter assay to screen 25,600 small molecules. Based on the dataset obtained from screening, a series of novel analogs of substituted benzamides containing azaspiro rings were assessed for their ability to induce the transcription of the Apo A-I gene, and the structure-activity relationship (SAR around these analogs was also proposed. The results indicated that the trifluoromethyl substituted benzamide containing an azaspiro ring is a promising backbone for designing Apo A-I transcriptional upregulator and could be viable leads for development of new drugs to prevent and treat atherosclerosis in the future.

  9. Determination of lipoprotein(a) concentrations and apolipoprotein(a) molecular weights in diabetic patients.

    Science.gov (United States)

    Ribault, A; Durou, M R; Letellier, C; Wojcik, F; Poirier, J Y; Ruelland, A

    2000-04-01

    Lipoprotein(a) (Lp(a)) with atherogenic and thrombotic properties has been frequently studied in diabetes, because a high cardiovascular risk has been reported both in type 1 and type 2 diabetes. Few studies have considered genetic factors, especially the isoforms of apolipoprotein(a). The aim of this work is to determine the distribution of apo(a) phenotypes in the serum of 148 diabetic patients (59 type 1, 89 type 2) with or without vascular complications. Apo(a) phenotypes are determined using 4-15% sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by immunoblotting (PhastSystem - Pharmacia). An inverse relationship is observed between Lp(a) serum concentration and the apparent molecular mass of apo(a) isoforms: type 1 r=- 0.61, p<0.01; type 2 r=- 0.55, p<0.01. The frequency of apo(a) isoforms is significantly different between type 1 and type 2 diabetes mellitus. A higher prevalence of isoforms of low molecular weight was observed in the type 2 diabetic population. PMID:10804324

  10. Apolipoprotein A5: A newly identified gene impacting plasmatriglyceride levels in humans and mice

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Rubin, Edward M.

    2002-09-15

    Apolipoprotein A5 (APOA5) is a newly described member of theapolipoprotein gene family whose initial discovery arose from comparativesequence analysis of the mammalian APOA1/C3/A4 gene cluster. Functionalstudies in mice indicated that alteration in the level of APOA5significantly impacted plasma triglyceride concentrations. Miceover-expressing human APOA5 displayed significantly reducedtriglycerides, while mice lacking apoA5 had a large increase in thislipid parameter. Studies in humans have also suggested an important rolefor APOA5 in determining plasma triglyceride concentrations. In theseexperiments, polymorphisms in the human gene were found to define severalcommon haplotypes that were associated with significant changes intriglyceride concentrations in multiple populations. Several separateclinical studies have provided consistent and strong support for theeffect with 24 percent of Caucasians, 35 percent of African-Americans and53 percent of Hispanics carrying APOA5 haplotypes associated withincreased plasma triglyceride levels. In summary, APOA5 represents anewly discovered gene involved in triglyceride metabolism in both humansand mice whose mechanism of action remains to be deciphered.

  11. Production of a soluble and functional recombinant apolipoproteinD in the Pichia pastoris expression system.

    Science.gov (United States)

    Armanmehr, Shiva; Kalhor, Hamid Reza; Tabarraei, Alijan

    2016-05-01

    ApolipoproteinD (ApoD) is a human glycoprotein from the lipocalin family. ApoD contains a conserved central motif of an 8-stranded antiparallel β-sheet, which forms a beta-barrel that can be used for transport and storage of diverse hydrophobic ligands. Due to hydrophobic nature of ApoD, it has been difficult to generate a recombinant version of this protein. In the present work, we aimed at the production of ApoD in the robust Pichia pastoris expression system. To this end, the ApoD gene sequence was synthesized and subcloned for expression in the yeast host cells. Following integration of the ApoD gene into the yeast genomic region using homologous recombination, the ApoD recombinant protein was induced using methanol, reaching its maximum induction at 96 h. Having purified the ApoD recombinant protein by affinity chromatography, we measured the dissociation constant (KD) using its natural ligands: progesterone and arachidonic acid. Our results provide a viable solution to the production of recombinant ApoD protein in lieu of previous obstacles in generating soluble and functional ApoD protein. PMID:26826316

  12. Psyllium husk. II: Effect on the metabolism of apolipoprotein B in African green monkeys.

    Science.gov (United States)

    McCall, M R; Mehta, T; Leathers, C W; Foster, D M

    1992-08-01

    Dietary psyllium's ability to reduce low-density-lipoprotein (LDL) cholesterol is presumably mediated by increased LDL catabolism and/or reduced LDL synthesis. To distinguish between these possibilities, apolipoprotein B (apo B) metabolism was studied in adult male African green monkeys consuming one of three semipurified diets: low-cholesterol cellulose (LCC), high-cholesterol cellulose (HCC), or high-cholesterol psyllium (HCP). 131I-labeled LDL and 125I-labeled VLDL were injected simultaneously into animals; blood samples were drawn at selected times and apo B specific activity determined in VLDL, IDL, and LDL. Based on a multicompartmental model, LDL apo B pool size and de novo apo B transport were elevated significantly in HCC animals compared with HCP and LCC animals. Differences in LDL transport, although not significant, paralleled differences observed in LDL apo B pool size. Fractional catabolic rates were similar among groups (HCC 0.040 +/- 0.010; HCP 0.042 +/- 0.009, and LCC 0.043 +/- 0.004 pools/h). These data suggest that dietary psyllium reduces plasma cholesterol concentrations by decreasing LDL synthesis. PMID:1322033

  13. Evaluation of Apolipoprotein A5 Polymorphism in Coronary- Heart Disease Patients

    Directory of Open Access Journals (Sweden)

    Somayeh Haqparast

    2012-02-01

    Full Text Available Background and Objectives: Apolipoprotein A5 (APOA5 gene is important in determining plasma triglyceride levels, a major cardiovascular disease risk factor. Mutation in this gene affected plasma triglyceride level. We looked for possible associations of the APOA5 gene polymorphism S19W with coronary heart disease (CHD in a sample of Iranian population. Materials and Methods: A total of 73 CHD patients and 55 controls were genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP for this single nucleotide polymorphism. Serum lipids and Fast Blood Sugar concentrations were measured in all subjects with enzymatic method. Results: Allele frequencies observed in our population were 0.041 for the W allele and 0.959 for the S allele which are similar to other populations (p>0.05. There is no evidence that APOA5 S19W, is a risk factor of CHD in our sample (p>0.05. In addition, we observed no association between the APOA5 W allele and elevated plasma TG levels (p>0.05 in the CHD group. This result was also present in the control group (p>0.05. Conclusion: The APO A5 gene polymorphism in S19W gene has no association with the high susceptibility to CHD.

  14. Capture and concentration of viral and bacterial foodborne pathogens using apolipoprotein H.

    Science.gov (United States)

    Almand, Erin A; Goulter, Rebecca M; Jaykus, Lee-Ann

    2016-09-01

    The need for improved pathogen separation and concentration methods to reduce time-to-detection for foodborne pathogens is well recognized. Apolipoprotein H (ApoH) is an acute phase human plasma protein that has been previously shown to interact with viruses, lipopolysaccharides (LPS) and bacterial proteins. The purpose of this study was to determine if ApoH was capable of binding and efficiently capturing two representative human norovirus strains (GI.1 and GII.4), a cultivable surrogate, and four bacterial pathogens (Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica serovar Enteritidis, and Staphylococcus aureus). Experiments were carried out using an ApoH-conjugated magnetic bead-based capture followed by pathogen detection using nucleic acid amplification. For all three viruses studied, >10% capture efficiency (microflora. A complementary plate-based capture assay showed that ApoH bound to a variety of human norovirus virus-like particles. ApoH has the potential to be a broadly reactive ligand for separating and concentrating representative foodborne pathogens, both bacteria and viruses. PMID:27439140

  15. Effects of Simvastatin on adiponectin and endothelial function in apolipoprotein E-deficient mice

    Institute of Scientific and Technical Information of China (English)

    Meng Liu; Donghua Yin; Ming Gui; Kejiang Cao

    2009-01-01

    0bjective:To investigate the effects of simvastatin,a 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibitor,on adiponectin and markers of endothelial function in apolipoprotein E-deficient mice at an early stage of atherosclerosis.Methods:Twenty-four 6-week old male apoE-deficient mice were randomly divided into two groups:control group(normal saline) and treatment group[simvastatin(5 mg/(kg·d)].Simvastatin was administered to treatment group mice by gavage and the same volume of normal saline was administered to control group mice by the same method for 4 weeks.Total cholesterol(TC),superoxide dismutase(SOD),malondialdehyde (MDA),and nitric oxide(NO) were measured by biochemical analysis,and adiponectin was measured by an ABC-ELISA method.Results:There was no significant difference in serum TC between control and treatment groups.Compared with the control animals,simvastafin-treated animals exhibited a significant increase in serurn levels of adponectin,SOD and NO,and decrease in serum MDA(P <0.01).Conclusion:Simvastatin protects endothelial function by increasing serum adiponectin,which may increase serum SOD and NO,and decrease serum MDA.This study suggests that sirnvastatin has therapeutic advantages,unrelated to its cholesterol-lowering effect,that are mediated by adiponectin.

  16. Molecular cloning and characterization of the promoter region of the porcine apolipoprotein E gene.

    Science.gov (United States)

    Xia, Jihan; Hu, Bingjun; Mu, Yulian; Xin, Leilei; Yang, Shulin; Li, Kui

    2014-05-01

    Apolipoprotein E (APOE), a component of lipoproteins plays an important role in the transport and metabolism of cholesterol, and is associated with hyperlipoproteinemia and Alzheimer's disease. In order to further understand the characterization of APOE gene, the promoter of APOE gene of Landrace pigs was analyzed in the present study. The genomic structure and amino acid sequence in pigs were analyzed and found to share high similarity in those of human but low similarity in promoter region. Real-time PCR revealed the APOE gene expression pattern of pigs in diverse tissues. The highest expression level was observed in liver, relatively low expression in other tissues, especially in stomach and muscle. Furthermore, the promoter expressing in Hepa 1-6 was significantly better at driving luciferase expression compared with C2C12 cell. After analysis of porcine APOE gene promoter regions, potential transcription factor binding sites were predicted and two GC signals, a TATA box were indicated. Results of promoter activity analysis indicated that one of potential regulatory elements was located in the region -669 to -259, which was essential for a high expression of the APOE gene. Promoter mutation and deletion analysis further suggested that the C/EBPA binding site within the APOE promoter was responsible for the regulation of APOE transcription. Electrophoretic mobility shift assays also showed the binding site of the transcription factor C/EBPA. This study advances our knowledge of the promoter of the porcine APOE gene. PMID:24464129

  17. Apolipoprotein E ε4 allele modulates the immediate impact of acute exercise on prefrontal function.

    Science.gov (United States)

    De Marco, Matteo; Clough, Peter J; Dyer, Charlotte E; Vince, Rebecca V; Waby, Jennifer S; Midgley, Adrian W; Venneri, Annalena

    2015-01-01

    The difference between Apolipoprotein E ε4 carriers and non-carriers in response to single exercise sessions was tested. Stroop and Posner tasks were administered to young untrained women immediately after walking sessions or moderately heavy exercise. Exercise had a significantly more profound impact on the Stroop effect than on the Posner effect, suggesting selective involvement of prefrontal function. A significant genotype-by-exercise interaction indicated differences in response to exercise between ε4 carriers and non-carriers. Carriers showed facilitation triggered by exercise. The transient executive down-regulation was construed as due to exercise-dependent hypofrontality. The facilitation observed in carriers was interpreted as better management of prefrontal metabolic resources, and explained within the antagonistic pleiotropy hypothesis framework. The findings have implications for the interpretation of differences between ε4 carriers and non-carriers in the benefits triggered by long-term exercise that might depend, at least partially, on mechanisms of metabolic response to physical activity. PMID:25218559

  18. Apolipoprotein E Genotype Linked to Spatial Gait Characteristics: Predictors of Cognitive Dual Task Gait Change

    Science.gov (United States)

    MacAulay, Rebecca K.; Allaire, Ted; Brouillette, Robert; Foil, Heather; Bruce-Keller, Annadora J.; Keller, Jeffrey N.

    2016-01-01

    Background Developing measures to detect preclinical Alzheimer’s Disease is vital, as prodromal stage interventions may prove more efficacious in altering the disease’s trajectory. Gait changes may serve as a useful clinical heuristic that precedes cognitive decline. This study provides the first systematic investigation of gait characteristics relationship with relevant demographic, physical, genetic (Apolipoprotein E genotype), and health risk factors in non-demented older adults during a cognitive-load dual task walking condition. Methods The GAITRite system provided objective measurement of gait characteristics in APOE-e4 “carriers” (n = 75) and “non-carriers” (n = 224). Analyses examined stride length and step time gait characteristics during simple and dual-task (spelling five-letter words backwards) conditions in relation to demographic, physical, genetic, and health risk factors. Results Slower step time and shorter stride length associated with older age, greater health risk, and worse physical performance (ps attention decrements and structural brain changes in older adults. Our results indicate that stride length is a useful behavioral marker of cognitive change that is associated with genetic risk for AD. Sex disparities in motor decline may be a function of health risk factors. PMID:27486898

  19. Phosphorylation-dependent down-regulation of apolipoprotein A5 by insulin

    Energy Technology Data Exchange (ETDEWEB)

    Nowak, Maxine; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Rommens, Corinne; Martin, Genevieve; Duran-Sandoval, Daniel; Staels, Bart; Rubin, Edward M.; Pennacchio, Len A.; Taskinen, Marja-Riitta; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-02-15

    The apolipoprotein A5 (APOA5) gene has been shown to be important in lowering plasma triglyceride levels. Since several studies have shown that hyperinsulinemia is associated with hypertriglyceridemia, we sought to determine whether APOA5 gene is regulated by insulin. We show here that cell and mouse treatments with insulin down-regulated APOA5 expression in a dose-dependent manner. Furthermore, we determined that insulin decreases APOA5 promoter activity and subsequent deletion analyses revealed an E-box-containing fragment. We showed that Upstream Stimulatory Factors, USF1/USF2, bind to the identified E-box in the APOA5 promoter. Moreover, in cotransfection studies, USF1 stimulates APOA5 promoter activity. The treatment with insulin reduces the binding of USF1/USF2 to APOA5 promoter. The inhibition of PI3K pathway with wortmannin abolished the insulin s effect on APOA5 gene transcription. Using oligoprecipitation method of USF from nuclear extracts, we demonstrated that phosphorylated USF1 failed to bind to APOA5 promoter. This indicates that the APOA5 gene transrepression by insulin involves a phosphorylation of USF through PI3K, that modulate their binding to APOA5 promoter and results in APOA5 down-regulation. The effect of exogenous hyperinsulinemia in healthy men shows a decrease of the plasma ApoAV level. These data suggest a potential mechanism involving APOA5 gene in hypertriglyceridemia associated with hyperinsulinemia.

  20. Intracellular trafficking of recycling apolipoprotein E in Chinese hamster ovary cells.

    Science.gov (United States)

    Braun, Nicole A; Mohler, Peter J; Weisgraber, Karl H; Hasty, Alyssa H; Linton, MacRae F; Yancey, Patricia G; Su, Yan Ru; Fazio, Sergio; Swift, Larry L

    2006-06-01

    We have investigated apolipoprotein E (apoE) recycling in Chinese hamster ovary (CHO) cells, a peripheral cell that does not produce lipoproteins or express apoE. Using a pulse-chase protocol in which cells were pulsed with 125I-apoE-VLDL and chased for different periods, approximately 30% of the apoE internalized during the pulse was resecreted within a 4 h chase in a relatively lipid-free state. The addition of lysosomotropic agents or brefeldin A had no effect on apoE recycling. Unlike previous results with hepatocytes and macrophages, neither apoA-I nor upregulation of ABCA1 stimulated apoE recycling. However, cyclodextrin, which extracts cholesterol from plasma membrane lipid rafts, increased recycling. Confocal studies revealed that apoE, internalized during a 1 h pulse, colocalizes with early endosomal antigen-1, Rab5, Rab11a, and lysobisphosphatidic acid but not with lysosomal-associated membrane protein-1. Colocalization of apoE and Rab11a persisted even after cells had been chased for 1 h, suggesting a pool of apoE within the endosomal recycling compartment (ERC). Our data suggest that apoE recycling in CHO cells is linked to cellular cholesterol removal via the ERC and phospholipid-containing acceptors in a pathway alternative to the ABCA1-apoA-I axis. PMID:16534141

  1. Relationship Between Plasma Insulin Level and Apolipoprotein E Gene Polymorphysm in Alzheimer′s Disease

    Institute of Scientific and Technical Information of China (English)

    Luo Zhuming; Yuan Qiang

    2000-01-01

    Objective: To study relationship between plasma insulin level and apolipoprotein E Gene polymorphysm in Alzheimcr′s Disease. Background: Recent researches have shown that there was a close relationship between ApoE- ε 4 allele and AD. Because of the discovery of hyperinsulineamia in AD patients, the study of insulin on the pathogenesis of AD become a hot point of AD reseearch. Methods: We apply PCR-RFLP to the ApoE genotype study of 45 AD paticnts and 32 normal controls. At the same time, plasma insulin and glucose level was measured in the abovc objects. Results and Discussion: The frequency of ApoE- ε 4 in AD (32.2%) is much higher than in controls (10.9%). On the contrary, the frequency of ApeE- ε 4 is relatively lower in AD than in thc controls. The resistence of hyperinsulineamia in AD. Insulin sensitivity decreased in AD. Conclusion: When gene dose of ApoE- ε 4 increases, the prcvalance of AD increase, while the on-set ages of AD decrease (P<0.05). These findings indicatc that AD patients may have insulin resistance anbd insulin probably play a role in AD pathogenesis. In addition, the s 4 homozygote AD patients seem to have loweer plasma insulin level that the non- ε 4 homozygote AD patients (P<0.05). But this situation need to be replicated in studies of larger sample.

  2. Meta-analysis of peripheral blood apolipoprotein E levels in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Chong Wang

    Full Text Available BACKGROUND: Peripheral blood Apolipoprotein E (ApoE levels have been proposed as biomarkers of Alzheimer's disease (AD, but previous studies on levels of ApoE in blood remain inconsistent. This meta-analysis was designed to re-examine the potential role of peripheral ApoE in AD diagnosis and its potential value as a candidate biomarker. METHODS: We conducted a systematic literature search of MEDLINE, EMBASE, the Cochrane library, and BIOSIS previews for case-control studies measuring ApoE levels in serum or plasma from AD subjects and healthy controls. The pooled weighted mean difference (WMD and 95% confidence interval (CI were used to estimate the association between ApoE levels and AD risk. RESULTS: Eight studies with a total of 2250 controls and 1498 AD cases were identified and analyzed. The pooled WMD from a random-effect model of AD participants compared with the healthy controls was -5.59 mg/l (95% CI: [-8.12, -3.06]. The overall pattern in WMD was not varied by characteristics of study, including age, country, assay method, publication year, and sample type. CONCLUSIONS: Our meta-analysis supports a lowered level of blood ApoE in AD patients, and indicates its potential value as an important risk factor for AD. Further investigation employing standardized assay for ApoE measurement are still warranted to uncover the precise role of ApoE in the pathophysiology of AD.

  3. Folded functional lipid-poor apolipoprotein A-I obtained by heating of high-density lipoproteins: relevance to high-density lipoprotein biogenesis.

    Science.gov (United States)

    Jayaraman, Shobini; Cavigiolio, Giorgio; Gursky, Olga

    2012-03-15

    HDL (high-density lipoproteins) remove cell cholesterol and protect from atherosclerosis. The major HDL protein is apoA-I (apolipoprotein A-I). Most plasma apoA-I circulates in lipoproteins, yet ~5% forms monomeric lipid-poor/free species. This metabolically active species is a primary cholesterol acceptor and is central to HDL biogenesis. Structural properties of lipid-poor apoA-I are unclear due to difficulties in isolating this transient species. We used thermal denaturation of human HDL to produce lipid-poor apoA-I. Analysis of the isolated lipid-poor fraction showed a protein/lipid weight ratio of 3:1, with apoA-I, PC (phosphatidylcholine) and CE (cholesterol ester) at approximate molar ratios of 1:8:1. Compared with lipid-free apoA-I, lipid-poor apoA-I showed slightly altered secondary structure and aromatic packing, reduced thermodynamic stability, lower self-associating propensity, increased adsorption to phospholipid surface and comparable ability to remodel phospholipids and form reconstituted HDL. Lipid-poor apoA-I can be formed by heating of either plasma or reconstituted HDL. We propose the first structural model of lipid-poor apoA-I which corroborates its distinct biophysical properties and postulates the lipid-induced ordering of the labile C-terminal region. In summary, HDL heating produces folded functional monomolecular lipid-poor apoA-I that is distinct from lipid-free apoA-I. Increased adsorption to phospholipid surface and reduced C-terminal disorder may help direct lipid-poor apoA-I towards HDL biogenesis. PMID:22150513

  4. Estrogen-responsive genes encoding egg yolk proteins vitellogenin and apolipoprotein II in chicken are differentially regulated by selective estrogen receptor modulators.

    Science.gov (United States)

    Ratna, Warren N; Bhatt, Vrushank D; Chaudhary, Kawshik; Bin Ariff, Ammar; Bavadekar, Supriya A; Ratna, Haran N

    2016-02-01

    In a hen, large quantities of the egg yolk proteins, apolipoprotein II (apo-II) and vitellogenin (VG), are expressed in the liver and transported to the oviduct during egg production. Estrogenic stimulation of the hepatic expression of apo-II and VG is due to both transcriptional increase and mRNA stabilization. The nucleolytic degradation of apo-II messenger RNA (mRNA) is prevented by estrogen-regulated mRNA-stabilizing factor (E-RmRNASF). Gene-specific effects of a select panel of selective estrogen receptor modulators (SERMs) on the hepatic expression of the estrogen-responsive genes encoding apo-II, VG, and E-RmRNASF in the chicken liver were investigated. In the present study, 6-week-old roosters were treated with the vehicle, estrogen, the SERMs genistein, resveratrol, tamoxifen, pterostilbene, raloxifene, catechin, and clomiphene or a combination of estrogen and a 200-fold excess of each of the SERMs. Results from mRNA stabilization studies conducted to investigate the stimulation of expression of E-RmRNASF in the liver by these agents showed that the expression of E-RmRNASF in the liver was stimulated by estrogen and the SERMs genistein, resveratrol, tamoxifen, pterostilbene, and catechin but not by the vehicle, clomiphene or raloxifene. The expression of apo-II and VG from the aforementioned treatments was determined by Northern blot analysis, RNase protection assays, and Western blot analysis. The transcription and protein expression of both apo-II and VG genes were seen in response to treatment with estrogen but not with the SERMs or combinations of estrogen and each of the SERMs. The SERMs that stimulated the expression of E-RmRNASF antagonized the stimulation of the expression of both apo-II and VG by estrogen, demonstrating a gene-specific, selective regulation of the aforementioned genes in the chicken liver by the SERMs. The above panel of SERMs may likely have adverse effects on egg production. PMID:26452509

  5. Prevalence of the apolipoprotein E Arg145Cys dyslipidemia at-risk polymorphism in African-derived populations.

    Science.gov (United States)

    Abou Ziki, Maen D; Strulovici-Barel, Yael; Hackett, Neil R; Rodriguez-Flores, Juan L; Mezey, Jason G; Salit, Jacqueline; Radisch, Sharon; Hollmann, Charleen; Chouchane, Lotfi; Malek, Joel; Zirie, Mahmoud A; Jayyuosi, Amin; Gotto, Antonio M; Crystal, Ronald G

    2014-01-15

    Apolipoprotein E, a protein component of blood lipid particles, plays an important role in lipid transport. Different mutations in the apolipoprotein E gene have been associated with various clinical phenotypes. In an initiated study of Qataris, we observed that 17% of the African-derived genetic subgroup were heterozygotes for a rare Arg145Cys (R145C) variant that functions as a dominant trait with incomplete penetrance associated with type III hyperlipoproteinemia. On the basis of this observation, we hypothesized that the R145C polymorphism might be common in African-derived populations. The prevalence of the R145C variant was assessed worldwide in the "1000 Genomes Project" and in 1,012 whites and 1,226 African-Americans in New York, New York. The 1000 Genomes Project data demonstrated that the R145C polymorphism is rare in non-African-derived populations but present in 5% to 12% of Sub-Saharan African-derived populations. The R145C polymorphism was also rare in New York whites (1 of 1,012, 0.1%); however, strikingly, 53 of the 1,226 New York African-Americans (4.3%) were R145C heterozygotes. The lipid profiles of the Qatari and New York R145C heterozygotes were compared with those of controls. The Qatari R145C subjects had higher triglyceride levels than the Qatari controls (p worldwide derived from Sub-Saharan Africans are apolipoprotein E R145C. In conclusion, although larger epidemiologic studies are necessary to determine the long-term consequences of this polymorphism, the available evidence suggests it is a common cause of a mild triglyceride dyslipidemia. PMID:24239320

  6. Comparison of deuterated leucine, valine, and lysine in the measurement of human apolipoprotein A-I and B-100 kinetics

    International Nuclear Information System (INIS)

    The production rates of apolipoprotein (apo)B-100 in very low density lipoprotein and in low density lipoprotein and apolipoprotein A-I in high density lipoprotein were determined using a primed-constant infusion of [5,5,5,-2H3]leucine, [4,4,4,-2H3]valine, and [6,6-2H2,1,2-13C2]lysine. The three stable isotope-labeled amino acids were administered simultaneously to determine whether absolute production rates calculated using a stochastic model were independent of the tracer species utilized. Three normolipidemic adult males were studied in the constantly fed state over a 15-h period. The absolute production rates of very low density lipoprotein apoB-100 were 11.4 +/- 5.8 (leucine), 11.2 +/- 6.8 (valine), and 11.1 +/- 5.4 (lysine) mg per kg per day (mean +/- SDM). The absolute production rates for low density lipoprotein apoB-100 were 8.0 +/- 4.7 (leucine), 7.5 +/- 3.8 (valine), and 7.5 +/- 4.2 (lysine) mg per kg per day. The absolute production rates for high density lipoprotein apoA-I were 9.7 +/- 0.2 (leucine), 9.4 +/- 1.7 (valine), and 9.1 +/- 1.3 (lysine) mg per kg per day. There were no statistically significant differences in absolute synthetic rates of the three apolipoproteins when the plateau isotopic enrichment values of very low density lipoprotein apoB-100 were used to define the isotopic enrichment of the intracellular precursor pool. Our data indicate that deuterated leucine, valine, or lysine provided similar results when used for the determination of apoA-I and apoB-100 absolute production rates within plasma lipoproteins as part of a primed-constant infusion protocol

  7. Against Stabilization

    Directory of Open Access Journals (Sweden)

    Roger Mac Ginty

    2012-11-01

    Full Text Available This is a polemic against the concept and practice of stabilization as practiced by leading states from the global north in peace support interventions. It is not an argument against stability. Instead, it depicts stabilization as an essentially conservative doctrine that runs counter to its stated aims of enhancing local participation and legitimacy. It is an agenda of control that privileges notions of assimilation with international (western standards and mainstreams the military into peace-support operations. As a result, the value of peace is undercut.

  8. Relevance of apolipoprotein E4 for the lipid profile of Brazilian patients with coronary artery disease

    Directory of Open Access Journals (Sweden)

    D.R.S. Souza

    2007-02-01

    Full Text Available Apolipoprotein E (apoE - e2, e3, e4 alleles plays a role in the regulation of lipid metabolism, with the e4 considered to be a risk factor for coronary artery disease (CAD. We aimed to evaluate the apoE polymorphisms in Brazilians with CAD and their influence on the lipid profile and other risk factors (hypertension, diabetes mellitus, smoking. Two hundred individuals were examined: 100 patients with atherosclerosis confirmed by coronary angiography and 100 controls. Blood samples were drawn to determine apoE polymorphisms and lipid profile. As expected, the e3 allele was prevalent in the CAD (0.87 and non-CAD groups (0.81; P = 0.099, followed by the e4 allele (0.09 and 0.14, respectively; P = 0.158. The e3/3 (76 and 78% and e3/4 (16 and 23% were the most common genotypes for patients and controls, respectively. The lipid profile was altered in patients compared to controls (P < 0.05, independently of the e4 allele. However, in the controls this allele was prevalent in individuals with elevated LDL-cholesterol levels only (odds ratio = 2.531; 95% CI = 1.028-6.232. The frequency of risk factors was higher in the CAD group (P < 0.05, but their association with the lipid profile was not demonstrable in e4 carriers. In conclusion, the e4 allele is not associated with CAD or lipid profile in patients with atherosclerosis. However, its frequency in the non-CAD group is associated with increased levels of LDL-cholesterol, suggesting an independent effect of the e4 allele on lipid profile when the low frequency of other risk factors in this group is taken into account.

  9. Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not triglyceride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Boerwinkle, E. (Univ. of Texas Health Science Center, Houston, TX (United States)); Brown, S.; Patsch, W. (Methodist Hospital and Baylor College of Medicine, Houston, TX (United States)); Sharrett, A.R. (National Heart, Lung, and Blood Institute, Bethesda, MD (United States)); Heiss, G. (Univ. of North Carolina, Chapel Hill, NC (United States))

    1994-02-01

    To quantify the effect of the apolipoprotein (apo) E polymorphism on the magnitude of postprandial lipemia, the authors have defined its role in determining the response to a single high-fat meal in a large sample of (N = 474) individuals taking part in the biethnic Atherosclerosis Risk in Communities Study. The profile of postprandial response in plasma was monitored over 8 h by triglyceride, triglyceride-rich lipoprotein (TGRL)-triglyceride, apo B-48/apo B-100 ratio, and retinyl palmitate concentrations, and the apo E polymorphism was determined by DNA amplification and digestion. The frequency of the apo E alleles and their effects on fasting lipid levels in this sample with vitamin A was significantly different among apo E genotypes, with delayed clearance in individuals with an [var epsilon]2 allele, compared with [var epsilon]3/3 and [var epsilon]3/4 individuals. In the sample of 397 Caucasians, average retinyl palmitate response was 1,489 [mu]g/dl in [var epsilon]2/3 individuals, compared with 1,037 [mu]g/dl in [var epsilon]3/3 individuals and 1,108 [mu]g/dl in [var epsilon]3/4 individuals. The apo E polymorphism accounted for 7.1% of the interindividual variation in postprandial retinyl palmitate response, a contribution proportionally greater than its well-known effect on fasting LDL-cholesterol. However, despite this effect on postprandial retinyl palmitate, the profile of postprandial triglyceride response was not significantly different among apo E genotypes. The profile of postprandial response was consistent between the sample of Caucasians and a smaller sample of black subjects. While these data indicate that the removal of remnant particles from circulation is delayed in subjects with the [var epsilon]2/3 genotype, there is no reported evidence that the [var epsilon]2 allele predisposes to coronary artery disease (CAD). 82 refs., 6 figs., 4 tabs.

  10. p53 family members regulate the expression of the apolipoprotein D gene.

    Science.gov (United States)

    Sasaki, Yasushi; Negishi, Hideaki; Koyama, Ryota; Anbo, Naoki; Ohori, Kanae; Idogawa, Masashi; Mita, Hiroaki; Toyota, Minoru; Imai, Kohzoh; Shinomura, Yasuhisa; Tokino, Takashi

    2009-01-01

    p73 and p63 are members of the p53 gene family that play an important role in development and homeostasis, mainly by regulating transcription of a variety of genes. We report here that apolipoprotein D (apoD), a member of the lipocalin superfamily of lipid transport proteins, is a direct transcriptional target of the p53 family member genes. We found that the expression of apoD was specifically up-regulated by either TAp73 or TAp63 but not significantly by p53. In addition, apoD transcription is activated in response to cisplatin in a manner dependent on endogenous p73. By using small interference RNA designed to target p73, we demonstrated that silencing endogenous p73 abolishes induction of apoD transcription following cisplatin treatment. We also identified a p73/p63-binding site in the promoter of the apoD gene that is responsive to the p53 family members. The ectopic expression of TAp73 as well as the addition of recombinant human apoD to culture medium induced the osteoblastic differentiation of the human osteosarcoma cell line Saos-2, as assessed by alkaline phosphatase activity. Importantly, apoD knockdown abrogated p73-mediated alkaline phosphatase induction. Moreover, TAp73-mediated apoD expression was able to induce morphological differentiation, as well as expression of neuronal markers, in the human neuroblastoma cell line SH-SY5Y. These results suggest that apoD induction may mediate the activity of p73 in normal development. PMID:19001418

  11. Clusterin/apolipoprotein J attenuates angiotensin II-induced renal fibrosis.

    Directory of Open Access Journals (Sweden)

    Gwon-Soo Jung

    Full Text Available The blockade of angiotensin II (Ang II is a major therapeutic strategy for diabetic nephropathy. The main roles of Ang II in renal disease are mediated via the Ang type 1 receptor (AT1R. Upregulation of clusterin/apolipoprotein J has been reported in nephropathy models, suggesting it has a protective role in nephropathogenesis. Here, we studied how clusterin acts against Ang II-induced renal fibrosis. Levels of AT1R and fibrotic markers in clusterin-/- mice and Ang II infused rats transfected with an adenovirus encoding clusterin were evaluated by immunoblot analysis, real time RT-PCR, and immunohistochemical staining. The effect of clusterin on renal fibrosis was evaluated in NRK-52E cells, a cultured renal tubular epithelial cell line, using immunoblot analysis and real time RT-PCR. Nuclear localization of NF-κB was evaluated using immunofluorecence and co-immunoprecipitation. Renal fibrosis and expression of AT1R was higher in the kidneys of clusterin-/- mice than in those of wild-type mice. Furthermore, loss of clusterin accelerated Ang II-stimulated renal fibrosis and AT1R expression. Overexpression of clusterin in proximal tubular epithelial cells decreased the levels of Ang II-stimulated fibrotic markers and AT1R. Moreover, intrarenal delivery of clusterin attenuated Ang II-mediated expression of fibrotic markers and AT1R in rats. Fluorescence microscopy and co-immunoprecipitation in conjunction with western blot revealed that clusterin inhibited Ang II-stimulated nuclear localization of p-NF-κB via a direct physical interaction and subsequently decreased the AT1R level in proximal tubular epithelial cells. These data suggest that clusterin attenuates Ang II-induced renal fibrosis by inhibition of NF-κB activation and subsequent downregulation of AT1R. This study raises the possibility that clusterin could be used as a therapeutic target for Ang II-induced renal diseases.

  12. Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Hong-Bo, E-mail: xhbzhb@yahoo.com [College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128 (China); Lu, Xiang-Yang; Sun, Zhi-Liang [Hunan Agricultural University, Changsha 410128 (China); Zhang, Heng-Bo [Furong District Red Cross Hospital, Changsha 410126 (China)

    2011-12-15

    Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE{sup -/-}) mice treated or not with kaempferol (50 or 100 mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE{sup -/-} mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. -- Graphical abstract: Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. Highlights: Black-Right-Pointing-Pointer OPN-CD44 pathway plays a critical role in the development of atherosclerosis. Black-Right-Pointing-Pointer We examine lesion area, OPN and CD44 changes after kaempferol treatment. Black-Right-Pointing-Pointer Kaempferol treatment decreased atherosclerotic lesion area in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol treatment decreased aortic OPN and CD44 expressions in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis.

  13. Blue-Green Algae Inhibit the Development of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice.

    Science.gov (United States)

    Ku, Chai Siah; Kim, Bohkyung; Pham, Tho X; Yang, Yue; Wegner, Casey J; Park, Young-Ki; Balunas, Marcy; Lee, Ji-Young

    2015-12-01

    Hyperlipidemia and inflammation contribute to the development of atherosclerotic lesions. Our objective was to determine antiatherogenic effect of edible blue-green algae (BGA) species, that is, Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), in apolipoprotein E knockout (ApoE(-/-)) mice, a well-established mouse model of atherosclerosis. Male ApoE(-/-) mice were fed a high-fat/high-cholesterol (HF/HC, 15% fat and 0.2% cholesterol by wt) control diet or a HF/HC diet supplemented with 5% (w/w) of NO or SP powder for 12 weeks. Plasma total cholesterol (TC) and triglycerides (TG) were measured, and livers were analyzed for histology and gene expression. Morphometric analysis for lesions and immunohistochemical analysis for CD68 were conducted in the aorta and the aortic root. NO supplementation significantly decreased plasma TC and TG, and liver TC, compared to control and SP groups. In the livers of NO-fed mice, less lipid droplets were present with a concomitant decrease in fatty acid synthase protein levels than the other groups. There was a significant increase in hepatic low-density lipoprotein receptor protein levels in SP-supplemented mice than in control and NO groups. Quantification of aortic lesions by en face analysis demonstrated that both NO and SP decreased aortic lesion development to a similar degree compared with control. While lesions in the aortic root were not significantly different between groups, the CD68-stained area in the aortic root was significantly lowered in BGA-fed mice than controls. In conclusion, both NO and SP supplementation decreased the development of atherosclerotic lesions, suggesting that they may be used as a natural product for atheroprotection. PMID:26566121

  14. Apolipoprotein A-I Helsinki promotes intracellular acyl-CoA cholesterol acyltransferase (ACAT) protein accumulation.

    Science.gov (United States)

    Toledo, Juan D; Garda, Horacio A; Cabaleiro, Laura V; Cuellar, Angela; Pellon-Maison, Magali; Gonzalez-Baro, Maria R; Gonzalez, Marina C

    2013-05-01

    Reverse cholesterol transport is a process of high antiatherogenic relevance in which apolipoprotein AI (apoA-I) plays an important role. The interaction of apoA-I with peripheral cells produces through mechanisms that are still poorly understood the mobilization of intracellular cholesterol depots toward plasma membrane. In macrophages, these mechanisms seem to be related to the modulation of the activity of acyl-CoA cholesterol acyltransferase (ACAT), the enzyme responsible for the intracellular cholesterol ester biosynthesis that is stored in lipid droplets. The activation of ACAT and the accumulation of lipid droplets play a key role in the transformation of macrophages into foam cells, leading to the formation of atheroma or atherosclerotic plaque. ApoA-I Helsinki (or ∆K107) is a natural apoA-I variant with a lysine deletion in the central protein region, carriers of which have increased atherosclerosis risk. We herein show that treatment of cultured RAW macrophages or CHOK1 cells with ∆K107, but not with wild-type apoA-I or a variant containing a similar deletion at the C-terminal region (∆K226), lead to a marked increase (more than 10 times) in the intracellular ACAT1 protein level as detected by western blot analysis. However, we could only detect a slight increase in cholesteryl ester produced by ∆K107 mainly when Chol loading was supplied by low-density lipoprotein (LDL). Although a similar choline-phospholipid efflux is evoked by these apoA-I variants, the change in phosphatidylcholine/sphyngomyelin distribution produced by wild-type apoA-I is not observed with either ∆K107 or ∆K226. PMID:23456478

  15. Apolipoprotein A-I metabolism in cynomolgus monkey. Identification and characterization of beta-migrating pools

    International Nuclear Information System (INIS)

    Fresh plasma from control (C) and hypercholesterolemic (HC) cynomolgus monkeys was analyzed by agarose electrophoresis-immunoblotting with antibody to cynomolgus monkey apolipoprotein (apo) A-I. Two bands were evident on the autoradiogram: an alpha-migrating band (high density lipoprotein) and a beta-migrating band that comigrated exactly with cynomolgus monkey low density lipoprotein (LDL). The presence of beta-migrating apo A-I in the plasma of these monkeys was confirmed by Geon-Pevikon preparative electrophoresis, crossed immunoelectrophoresis, and isotope dilution studies in which radiolabeled apo A-I was found to equilibrate also with alpha- and beta-migrating pools of apo A-I in the plasma. Subfractionation of C and HC plasma by agarose column chromatography (Bio-Gel A-0.5M and A-15M) followed by agarose electrophoresis-immunoblotting indicated that the beta-migrating apo A-I in C was relatively homogeneous and eluted with proteins of Mr approximately 50 kD [apo A-I(50 kD)], whereas two beta-migrating fractions were identified in HC, one that eluted with the 50-kD proteins, and the other that eluted in the LDL Mr range [apo A-I(LDL)]. The apo A-I(LDL) was precipitated by antibody to cynomolgus monkey apo B. The apo A-I(50 kD) accounted for 5 +/- 1% (mean +/- SD) of the plasma apo A-I in C plasma, and 15 +/- 7% in HC plasma. No apo A-I(LDL) was detected in C plasma, but that fraction accounted for 9 +/- 7% of the apo A-I in HC plasma. These data establish the presence of multiple pools of apo A-I in the cynomolgus monkey, which must be taken into consideration in any comprehensive model of apo A-I metabolism in this species

  16. CHRNA7 Polymorphisms and Dementia Risk: Interactions with Apolipoprotein ε4 and Cigarette Smoking.

    Science.gov (United States)

    Weng, Pei-Hsuan; Chen, Jen-Hau; Chen, Ta-Fu; Sun, Yu; Wen, Li-Li; Yip, Ping-Keung; Chu, Yi-Min; Chen, Yen-Ching

    2016-01-01

    α7 nicotinic acetylcholine receptor (α7nAChR, encoded by CHRNA7) is involved in dementia pathogenesis through cholinergic neurotransmission, neuroprotection and interactions with amyloid-β. Smoking promotes atherosclerosis and increases dementia risk, but nicotine exerts neuroprotective effect via α7nAChR in preclinical studies. No studies explored the gene-gene, gene-environment interactions between CHRNA7 polymorphism, apolipoprotein E (APOE) ε4 status and smoking on dementia risk. This case-control study recruited 254 late-onset Alzheimer's disease (LOAD) and 115 vascular dementia (VaD) cases (age ≥65) from the neurology clinics of three teaching hospitals in Taiwan during 2007-2010. Controls (N = 435) were recruited from health checkup programs and volunteers during the same period. Nine CHRNA7 haplotype-tagging single nucleotide polymorphisms representative for Taiwanese were genotyped. Among APOE ε4 non-carriers, CHRNA7 rs7179008 variant carriers had significantly decreased LOAD risk after correction for multiple tests (GG + AG vs. AA: adjusted odds ratio = 0.29, 95% confidence interval = 0.13-0.64, P = 0.002). Similar findings were observed for carriers of GT haplotype in CHRNA7 block4. A significant interaction was found between rs7179008, GT haplotype in block4 and APOE ε4 on LOAD risk. rs7179008 variant also reduced the detrimental effect of smoking on LOAD risk. No significant association was found between CHRNA7 and VaD. These findings help to understand dementia pathogenesis. PMID:27249957

  17. Apolipoprotein E expression and behavioral toxicity of high charge, high energy (HZE) particle radiation

    International Nuclear Information System (INIS)

    Apolipoprotein E (apoE) is a lipid binding protein that plays an important role in tissue repair following brain injury. In the present studies, we have investigated whether apoE affects the behavioral toxicity of high charge, high energy (HZE) particle radiation. Sixteen male apoE knockout (KO) mice and sixteen genetically matched wild-type (WT) C57BL mice were used in this experiment. Half of the KO and half of the WT animals were irradiated with 600 MeV/amu iron particles (2 Gy whole body). The effect of irradiation on motor coordination and stamina (Rotarod test), exploratory behavior (open field test), and spatial working and reference memory (Morris water maze) was assessed. Rotarod test: Performance was adversely affected by radiation exposure in both KO and WT groups at 30 d after irradiation. By 60 d after radiation, the radiation effect was lost in WT, but still apparent in irradiated KO mice. Open field test: Radiation reduced open field exploratory activity 14, 28, 56, 84, and 168 d after irradiation of KO mice, but had no effect on WT mice. Morris water maze: Radiation adversely affected spatial working memory in the KO mice, but had no discernible effect in the WT mice as assessed 180 d after irradiation. In contrast, irradiated WT mice showed marked impairment of spatial reference memory in comparison to non-irradiated mice, while no effect of radiation was observed in KO mice. These studies show that apoE expression influences the behavioral toxicity of HZE particle radiation and suggest that apoE plays a role in the repair/recovery from radiation injury of the central nervous system (CNS). ApoE deficiency may exacerbate the previously reported effects of HZE particle radiation in accelerating the brain aging process. (author)

  18. Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Olivier, Michael; Hubacek, Jaroslav A.; Krauss, Ronald M.; Rubin, Edward M.; Cohen, Jonathan C.

    2002-09-16

    The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in {approx}16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n 1/4 419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12 percent of Caucasians, 14 percent of African-Americans and 28 percent of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 50 percent of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

  19. Effects of simvastatin on early oxidative stress and endothelial function in apolipoprotein E-deficient mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To investigate the mechanisms that Simvastatin,a 3-ydroxy-3-methylglutaryl coenzyme A(HMG-CoA)reductase inhibitor,plays an important role in primary prevention of atherosclerosis independently of its lipid-lowering effect in Apolipoprotein E-deficient mice in the early stage of atherosclerosis.Methods:Twenty-four 6-week old male apoE-deficient mice were randomly divided into two groups:control group(normal saline)and treatment group[simvastatin(5 mg/(kg·d))].Simvastatin was administered to treatment group mice by gavage and the same volume of normal saline was administered to control group mice by the same method for 2 or 4 weeks.Total cholesterol(TC),super-oxide dismutase(SOD),malondialdehyde(MDA)and serum nitric oxide(NO)were measured by biochemical analysis.Results:There was no significant difference in serum TC between control and treatment groups.Compared with the control's,the effects of simvastatin were more signiticant in decreasing serum MDA level(P<0.01 vs control's at 2-week;P<0.006 vs control's at 4-week),increasing serum SOD level(P<0.03 vs control's at 2-week;P<0.003 vs control's at 4-week)and NO level (P<0.01 control's at 2-week;P<0.001 vs control's at 4-week)either at 2 or 4 weeks.Conclusion:Simvastatin attenuates oxidative stress and protects endothelial function by the mechanisms of decreasing serum MDA level,increasing serum SOD level and NO level,which were inconsistent with its cholesterol-lowering effect.It may play an important role in primary(if not all)prevention of atherosclerosis and might be independent of lipid-regulation mechanism.

  20. Inhibition of endoplasmic reticulum stress and atherosclerosis by 2-aminopurine in apolipoprotein e-deficient mice.

    Science.gov (United States)

    Zhou, Lichun; Yang, Dezhi; Wu, Dong Fang; Guo, Zhong Mao; Okoro, Emmanuel; Yang, Hong

    2013-01-01

    We previously reported that the apolipoprotein (apo) B48-carrying lipoproteins obtained from apoE knockout (apoE (-/-) ) mice, so called E(-)/B48 lipoproteins, transformed mouse macrophages into foam cells and enhanced the phosphorylation of eukaryotic translation initiation factor 2 α (eIF-2 α ). Furthermore, the eIF-2 α phosphorylation inhibitor, 2-aminopurine (2-AP), attenuated E(-)/B48 lipoprotein-induced foam cell formation. The present report studied the effect of 2-AP on atherosclerosis in apoE (-/-) mice. Our results showed that the level of food intake, bodyweight, plasma cholesterol, and triglycerides was comparable in apoE (-/-) mice treated with or without 2-AP. However, the mean size of atherosclerotic lesions in the aorta sinus as well as the surface area of the entire aorta of 2-AP-treated apoE (-/-) mice were reduced by about 55% and 39%, respectively, compared to samples from untreated control apoE (-/-) mice. In addition, the 2-AP-treated apoE (-/-) mice showed a significant decrease in glucose-regulated protein 78 (GRP78) and phosphorylated eIF-2 α in their aortic samples as compared to levels in untreated control apoE (-/-) mice. These observations suggest that endoplasmic reticulum stress is a causal mechanism for the development of atherosclerosis in apoE (-/-) mice and that therapeutic strategies can be developed for using eIF-2 α phosphorylation inhibitors, such as 2-AP, to prevent or treat atherosclerosis. PMID:23984090

  1. Synergistic effects of high fat feeding and apolipoprotein E deletion on enterocytic amyloid-beta abundance

    Directory of Open Access Journals (Sweden)

    Dhaliwal Satvinder S

    2008-04-01

    Full Text Available Abstract Background Amyloid-β (Aβ, a key protein found in amyloid plaques of subjects with Alzheimer's disease is expressed in the absorptive epithelial cells of the small intestine. Ingestion of saturated fat significantly enhances enterocytic Aβ abundance whereas fasting abolishes expression. Apolipoprotein (apo E has been shown to directly modulate Aβ biogenesis in liver and neuronal cells but it's effect in enterocytes is not known. In addition, apo E modulates villi length, which may indirectly modulate Aβ as a consequence of differences in lipid absorption. This study compared Aβ abundance and villi length in wild-type (WT and apo E knockout (KO mice maintained on either a low-fat or high-fat diet. Wild-type C57BL/6J and apo E KO mice were randomised for six-months to a diet containing either 4% (w/w unsaturated fats, or chow comprising 16% saturated fats and 1% cholesterol. Quantitative immunohistochemistry was used to assess Aβ abundance in small intestinal enterocytes. Apo E KO mice given the low-fat diet had similar enterocytic Aβ abundance compared to WT controls. Results The saturated fat diet substantially increased enterocytic Aβ in WT and in apo E KO mice, however the effect was greater in the latter. Villi height was significantly greater in apo E KO mice than for WT controls when given the low-fat diet. However, WT mice had comparable villi length to apo E KO when fed the saturated fat and cholesterol enriched diet. There was no effect of the high-fat diet on villi length in apo E KO mice. Conclusion The findings of this study are consistent with the notion that lipid substrate availability modulates enterocytic Aβ. Apo E may influence enterocytic lipid availability by modulating absorptive capacity.

  2. Leptospiral LruA is required for virulence and modulates an interaction with mammalian apolipoprotein AI.

    Science.gov (United States)

    Zhang, Kunkun; Murray, Gerald L; Seemann, Torsten; Srikram, Amporn; Bartpho, Thanatchaporn; Sermswan, Rasana W; Adler, Ben; Hoke, David E

    2013-10-01

    Leptospirosis is a worldwide zoonosis caused by spirochetes of the genus Leptospira. While understanding of pathogenesis remains limited, the development of mutagenesis in Leptospira has provided a powerful tool for identifying novel virulence factors. LruA is a lipoprotein that has been implicated in leptospiral uveitis as a target of the immune response. In this study, two lruA mutants, M754 and M765, generated by transposon mutagenesis from Leptospira interrogans serovar Manilae, were characterized. In M754, the transposon inserted in the middle of lruA, resulting in no detectable expression of LruA. In M765, the transposon inserted toward the 3' end of the gene, resulting in expression of a truncated protein. LruA was demonstrated to be on the cell surface in M765 and the wild type (WT). M754, but not M765, was attenuated in a hamster model of acute infection. A search for differential binding to human serum proteins identified a serum protein of around 30 kDa bound to the wild type and the LruA deletion mutant (M754), but not to the LruA truncation mutant (M765). Two-dimensional separation of proteins from leptospiral cells incubated with guinea pig serum identified the 28-kDa apolipoprotein A-I (ApoA-I) as a major mammalian serum protein that binds Leptospira in vitro. Interestingly, M754 (with no detectable LruA) bound more ApoA-I than did the LruA-expressing strains Manilae wild type and M765. Our data thus identify LruA as a surface-exposed leptospiral virulence factor that contributes to leptospiral pathogenesis, possibly by modulating cellular interactions with serum protein ApoA-I. PMID:23918777

  3. Liver expression of steroid hormones and Apolipoprotein D receptors in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    FJ Vizoso; L Rodrigo; M Rodriguez; A Altadill; ML González-Diéguez; A Linares; LO González; S Junquera; F Fresno-Forcelledo; MD Corte

    2007-01-01

    AIM: To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis.METHODS We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls)to determine the presence of specific antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitive score based on their intensity, and the percentage of immunostained cells was measured.RESULTS: A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However,the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis.CONCLUSION: Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies.

  4. Functional network endophenotypes unravel the effects of apolipoprotein E epsilon 4 in middle-aged adults.

    Directory of Open Access Journals (Sweden)

    Joseph S Goveas

    Full Text Available Apolipoprotein E-ε4 (APOE-ε4 accentuates memory decline, structural volume loss and cerebral amyloid deposition in cognitively healthy adults. We investigated whether APOE-ε4 carriers will show disruptions in the intrinsic cognitive networks, including the default mode (DMN, executive control (ECN and salience (SN networks, relative to noncarriers in middle-aged healthy adults; and the extent to which episodic-memory performance is related to the altered functional connectivity (Fc in these networks. Resting-state functional connectivity MRI (R-fMRI was used to measure the differences in the DMN, ECN and SN Fc between 20 APOE-ε4 carriers and 26 noncarriers. Multiple linear regression analyses were performed to determine the relationship between episodic-memory performance and Fc differences in the three resting-state networks across all subjects. There were no significant differences in the demographic and neuropsychological characteristics and the gray-matter volumes in the carriers and noncarriers. While mostly diminished DMN and ECN functional connectivities were seen, enhanced connections to the DMN structures were found in the SN in ε4 carriers. Altered DMN and ECN were associated with episodic memory performance. Significant Fc differences in the brain networks implicated in cognition were seen in middle-aged individuals with a genetic risk for AD, in the absence of cognitive decline and gray-matter atrophy. Prospective studies are essential to elucidate the potential of R-fMRI technique as a biomarker for predicting conversion from normal to early AD in healthy APOE-ε4 carriers.

  5. Radiative-SPR platform for the detection of apolipoprotein E for use in medical diagnostics

    Science.gov (United States)

    Sciacca, Beniamino; Francois, Alexandre; Penno, Megan A. S.; Brazzatti, Julie A.; Klingler-Hoffmann, Manuela; Hoffmann, Peter; Monro, Tanya M.

    2012-03-01

    Surface Plasmon Resonance (SPR) based sensors enable the rapid, label-free and highly sensitive detection of a large range of biomolecules. We have previously shown that, using silver coated optical fibres with an high surface roughness, a re-scattering of the surface plasmons is possible, turning SPR into a radiative process. This approach overcomes limitations associated with current SPR technologies such as the tight tolerance on the metallic coating thickness, and results in a more compact, versatile, robust and cost-effective approach. However, the specific detection of small molecules is a challenge in SPR systems, regardless of the SPR architecture that is used. This new sensing platform, which has proved effective for the detection of large molecules such as viruses, is now demonstrated to be able to detect small proteins thanks to an improved surface functionalization procedure, a key point for reliable and robust immunosensors. Avidin, a tetrameric biotin-binding protein, was used to link biotinylated antibodies to the biotinylated surface, with a given orientation, to enable efficient sensing of the analyte. This approach may offer significant advantages compared to protein A surface functionalization strategies such as a limited cross reactivity with free IgG antibodies in clinical samples. We demonstrate that by bringing together this novel emission-based fibre SPR platform, with an improved surface functionalization process, is possible to rapidly and specifically detect human apolipoprotein E, a low molecular weight protein (~39kDa) known to be involved in cardiovascular diseases, in Alzheimer's disease and in gastric cancer. The results obtained clearly show that this new sensing platform has the potential to serve as a tool for point-of-decision medical diagnostics.

  6. Postmenopausal Osteoporosis Is Associated with Serum Chemerin and Irisin but Not with Apolipoprotein M Levels

    Science.gov (United States)

    Çağlayan, Emel Kıyak; Göçmen, Ayşe Yeşim; Polat, Muhammed Fevzi

    2016-01-01

    Objectives The objective of this study was to describe the levels of chemerin, irisin and apolipoprotein M (apoM) in women with postmenopausal osteoporosis. Methods The study included 88 women with postmenopausal osteoporosis. Based on World Health Organization criteria, women with a T-score of ≤ –2.5 were defined as osteoporotic. In this case-control study, postmenopausal women with T-score > –1 were selected as controls (n = 88) and case-matched in a 1:1 ratio based on age (within 2 years) and body mass index (BMI) (within 1.0 kg/m2). ApoM, irisin and chemerin levels were determined by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results There were no significant differences in age, BMI, parity, cholesterol and apoM levels between the two groups. C-reactive protein levels were significantly increased in women with osteoporosis. Serum chemerin levels (240.1 ± 46.1 vs. 261.5 ± 50.8 ng/mL) were significantly lower in the women with osteoporosis, as compared to the controls (P = 0.004). Serum irisin levels were also decreased in women with osteoporosis (0.7 ± 0.2 vs. 0.8 ± 0.2 ng/mL; P = 0.007). Conclusion In the present study, osteoporosis was associated with decreased levels of circulating chemerin and irisin. These findings suggested that adipokines might play a role in the pathogenesis of osteoporosis.

  7. Apolipoprotein B-containing lipoprotein assembly in microsomal triglyceride transfer protein-deficient McA-RH7777 cells

    OpenAIRE

    Liu, Yanwen; Manchekar, Medha; Sun, Zhihuan; Richardson, Paul E.; Dashti, Nassrin

    2010-01-01

    Microsomal triglyceride transfer protein (MTP) is required for the assembly and secretion of apolipoprotein (apo) B-containing lipoproteins. Previously, we demonstrated that the N-terminal 1,000 residues of apoB (apoB:1000) are necessary for the initiation of apoB-containing lipoprotein assembly in rat hepatoma McA-RH7777 cells and that these particles are phospholipid (PL) rich. To determine if the PL transfer activity of MTP is sufficient for the assembly and secretion of primordial apoB:10...

  8. Apolipoprotein E Variation at the Sequence Haplotype Level: Implications for the Origin and Maintenance of a Major Human Polymorphism

    OpenAIRE

    Fullerton, Stephanie M.; Clark, Andrew G.; Weiss, Kenneth M.; Nickerson, Deborah A.; Taylor, Scott L.; Stengård, Jari H.; Salomaa, Veikko; Vartiainen, Erkki; Perola, Markus; Boerwinkle, Eric; Sing, Charles F.

    2000-01-01

    Three common protein isoforms of apolipoprotein E (apoE), encoded by the ε2, ε3, and ε4 alleles of the APOE gene, differ in their association with cardiovascular and Alzheimer's disease risk. To gain a better understanding of the genetic variation underlying this important polymorphism, we identified sequence haplotype variation in 5.5 kb of genomic DNA encompassing the whole of the APOE locus and adjoining flanking regions in 96 individuals from four populations: blacks from Jackson, MS (n=4...

  9. High 99mTc-DPD myocardial uptake in a patient with apolipoprotein AI-related amyloidotic cardiomyopathy.

    Science.gov (United States)

    Quarta, Candida Cristina; Obici, Laura; Guidalotti, Pier Luigi; Pieroni, Maurizio; Longhi, Simone; Perlini, Stefano; Verga, Laura; Merlini, Giampaolo; Rapezzi, Claudio

    2013-03-01

    Amyloidotic cardiomyopathy is still a widely underdiagnosed condition that usually requires endomyocardial biopsy (EMB) for a definite diagnosis. 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has proven highly sensitive for detecting amyloidotic cardiomyopathy due to transthyretin-related amyloid deposition. Herein we report the first description of the (99mTc-DPD scintigraphy profile in a patient with suspected amyloidotic cardiomyopathy and a final EMB- and genetically-proven diagnosis of familial apolipoprotein AI amyloidosis due to Leu174Ser variant. PMID:23231421

  10. Depression and Plasma Amyloid β Peptides in the Elderly with and without the Apolipoprotein E4 Allele

    OpenAIRE

    Sun, Xiaoyan; Chiu, Chi Chia; Liebson, Elizabeth; Crivello, Natalia A.; Wang, Lixia; Caunch, Joshua; Folstein, Marshal; Rosenberg, Irwin; Mwamburi, D. Mkaya; Peter, Inga; Qiu, Wei Qiao

    2009-01-01

    Depression associated with low plasma Amyloid-β peptide 42 (Aβ42) leading to a high ratio of Aβ40/Aβ42, a biomarker of Alzheimer’s disease (AD), may represent a unique depression subtype. The relationship between low plasma Aβ42 in depression and the major risk factor of AD, Apolipoprotein E4 (ApoE4), is unknown. With the goal of clarifying this relationship, we analyzed 1060 homebound elders with ApoE characterization and depression status in a cross-sectional study. Plasma Aβ40 and Aβ42 wer...

  11. Kringle-containing fragments of apolipoprotein(a) circulate in human plasma and are excreted into the urine.

    OpenAIRE

    Mooser, V.; Marcovina, S. M.; A L White; Hobbs, H H

    1996-01-01

    Apolipoprotein(a) [apo(a)] contains multiple kringle 4 repeats and circulates as part of lipoprotein(a) [Lp(a)]. Apo(a) is synthesized by the liver but its clearance mechanism is unknown. Previously, we showed that kringle 4-containing fragments of apo(a) are present in human urine. To probe their origin, human plasma was examined and a series of apo(a) immunoreactive peptides larger in size than urinary fragments was identified. The concentration of apo(a) fragments in plasma was directly re...

  12. Lactobacillus acidophilus ATCC 4356 Prevents Atherosclerosis via Inhibition of Intestinal Cholesterol Absorption in Apolipoprotein E-Knockout Mice

    OpenAIRE

    Huang, Ying; WANG, Jinfeng; Quan, Guihua; Wang, Xiaojun; Yang, Longfei; Zhong, Lili

    2014-01-01

    The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE−/−) mice. Eight-week-old ApoE−/− mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE−/− mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption cau...

  13. A gel-based method for purification of apolipoprotein A-I from small volumes of plasma

    OpenAIRE

    Brace, Rachel J.; Sorrenson, Brie; Sviridov, Dmitri; McCormick, Sally P. A.

    2010-01-01

    We present here a gel-based method for rapid purification of apolipoprotein A-I (apoA-I) from small volumes of human plasma. After isolation of high density lipoprotein from plasma, the apoA-I protein was separated by electrophoresis and the apoA-I band excised from the gel. The apoA-I was then eluted from the gel strip, concentrated, and delipidated ready for use. The structure and function of the gel-purified apoA-I protein was compared against apoA-I purified by the traditional size-exclus...

  14. Apolipoprotein B Is Related to Metabolic Syndrome Independently of Low Density Lipoprotein Cholesterol in Patients with Type 2 Diabetes

    OpenAIRE

    Lim, Younghyup; Yoo, Soyeon; Lee, Sang Ah; Chin, Sang Ouk; Heo, Dahee; Moon, Jae Cheol; Moon, Shinhang; Boo, Kiyoung; Kim, Seong Taeg; Seo, Hye Mi; Jwa, Hyeyoung; Koh, Gwanpyo

    2015-01-01

    Background Increased low density lipoprotein cholesterol (LDL-C) level and the presence of metabolic syndrome (MetS) are important risk factors for cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). Recent studies demonstrated apolipoprotein B (apoB), a protein mainly located in LDL-C, was an independent predictor of the development of CVD especially in patients with T2DM. The aim of this study was to investigate the relationship between apoB and MetS in T2DM patients. Methods W...

  15. Comparison of immunoturbidimetric and Lowry methods for measuring concentration of very low density lipoprotein apolipoprotein B-100 in plasma.

    OpenAIRE

    Cummings, M H; Watts, G F; Lumb, P J; Slavin, B M

    1994-01-01

    To assess whether the Lowry-tetramethylurea method for measuring apolipoprotein B-100 (apo-B) in very low density lipoprotein (VLDL) could be replaced by direct assay of VLDL apo-B using a highly practicable immunological method. Seventy five fasting blood samples were collected from patients attending the lipid clinic at this hospital. Plasma was separated immediately and VLDL isolated by preparative ultracentrifugation at solution density 0.93-1.006 kg/l. Apo-B was precipitated from an aliq...

  16. Regeneration-associated high level expression of apolipoprotein D mRNA in endoneurial fibroblasts of peripheral nerve.

    OpenAIRE

    Spreyer, P; Schaal, H; Kuhn, G.; Rothe, T; Unterbeck, A; Olek, K; Müller, H. W.

    1990-01-01

    A cDNA clone containing the entire coding region of rat apolipoprotein D (Apo D) was isolated from a cDNA library of regenerating sciatic nerve by differential hybridization. Only small amounts of Apo D mRNA were detected in noninjured mature nerve. Moderately increased levels of Apo D transcripts were found in transected nerves, which were prevented from regeneration by ligation. In contrast, in regenerating crushed nerve, the steady-state level of Apo D mRNA transiently increased at least 4...

  17. Transcriptional regulation of the apolipoprotein B100 gene: purification and characterization of trans-acting factor BRF-2.

    OpenAIRE

    Zhuang, H.; Chuang, S S; Das, H. K.

    1992-01-01

    Apolipoprotein B100 (apoB), the only protein of low-density lipoprotein, is produced primarily in the liver and serves as a ligand for the low-density lipoprotein receptor. Hepatic cell-specific expression of the human apoB gene is controlled by at least two cis-acting positive elements located between positions-128 and -70 (H. K. Das, T. Leff, and J.L. Breslow, J. Biol. Chem. 263:11452-11458, 1988). The distal element (-128 to -85) appears to be liver specific since it shows positive activit...

  18. Susceptibility of Mice to Trypanosoma evansi Treated with Human Plasma Containing Different Concentrations of Apolipoprotein L-1

    OpenAIRE

    Aleksandro S. Da Silva; Fanfa, Vinicius R.; Otto, Mateus A.; Gressler, Lucas T.; Tavares, Kaio C.S.; Lazzarotto, Cícera R.; Alexandre A Tonin; Miletti, Luiz C.; Duarte, Marta M. M. F.; Silvia G. Monteiro

    2011-01-01

    The aim of this study was to test the susceptibility of mice to Trypanosoma evansi treated with human plasma containing different concentrations of apolipoprotein L-1 (APOL1). For this experiment, a strain of T. evansi and human plasma (plasmas 1, 2, and 3) from 3 adult males clinically healthy were used. In vivo test used 50 mice divided in 5 groups (A to E) with 10 animals in each group. Animals of groups B to E were infected, and then treated with 0.2 ml of human plasma in the following ou...

  19. Apolipoprotein E Regulates the Integrity of Tight Junctions in an Isoform-dependent Manner in an in Vitro Blood-Brain Barrier Model*

    OpenAIRE

    Nishitsuji, Kazuchika; Hosono, Takashi; Nakamura, Toshiyuki; Bu, Guojun; Michikawa, Makoto

    2011-01-01

    Apolipoprotein E (apoE) is a major apolipoprotein in the brain. The ϵ4 allele of apoE is a major risk factor for Alzheimer disease, and apoE deficiency in mice leads to blood-brain barrier (BBB) leakage. However, the effect of apoE isoforms on BBB properties are as yet unknown. Here, using an in vitro BBB model consisting of brain endothelial cells and pericytes prepared from wild-type (WT) mice, and primary astrocytes prepared from human apoE3- and apoE4-knock-in mice, we show that the barri...

  20. Immunotherapeutic and toxic effects of a triple fusion protein encompassing apolipoprotein A-I, IL-15 and IL-15Rα sushi domain

    OpenAIRE

    María C Ochoa; Inmaculada Rodriguez; Guillermo Mazzolini

    2013-01-01

    Interleukin 15 (IL-15) effects on CD8 T and NK lymphocytes hold promise to treat cancer. Fusion proteins have been engineered to provide IL-15 receptor alpha (IL-15Rα) mediated trans-presentation to lymphocytes and extend the plasma half-life of the cytokine. In this study, we report on a triple fusion protein combining apolipoprotein A-I, IL-15 and IL-15Rα’s sushi domain. Apolipoprotein A-I conveys IL-15 to high-density lipoproteins (HDL), from which the cytokine is trans-presented by the IL...

  1. Zebrafish as a model for apolipoprotein biology: comprehensive expression analysis and a role for ApoA-IV in regulating food intake

    Directory of Open Access Journals (Sweden)

    Jessica P. Otis

    2015-03-01

    Full Text Available Improved understanding of lipoproteins, particles that transport lipids throughout the circulation, is vital to developing new treatments for the dyslipidemias associated with metabolic syndrome. Apolipoproteins are a key component of lipoproteins. Apolipoproteins are proteins that structure lipoproteins and regulate lipid metabolism through control of cellular lipid exchange. Constraints of cell culture and mouse models mean that there is a need for a complementary model that can replicate the complex in vivo milieu that regulates apolipoprotein and lipoprotein biology. Here, we further establish the utility of the genetically tractable and optically clear larval zebrafish as a model of apolipoprotein biology. Gene ancestry analyses were implemented to determine the closest human orthologs of the zebrafish apolipoprotein A-I (apoA-I, apoB, apoE and apoA-IV genes and therefore ensure that they have been correctly named. Their expression patterns throughout development were also analyzed, by whole-mount mRNA in situ hybridization (ISH. The ISH results emphasized the importance of apolipoproteins in transporting yolk and dietary lipids: mRNA expression of all apolipoproteins was observed in the yolk syncytial layer, and intestinal and liver expression was observed from 4–6 days post-fertilization (dpf. Furthermore, real-time PCR confirmed that transcription of three of the four zebrafish apoA-IV genes was increased 4 hours after the onset of a 1-hour high-fat feed. Therefore, we tested the hypothesis that zebrafish ApoA-IV performs a conserved role to that in rat in the regulation of food intake by transiently overexpressing ApoA-IVb.1 in transgenic larvae and quantifying ingestion of co-fed fluorescently labeled fatty acid during a high-fat meal as an indicator of food intake. Indeed, ApoA-IVb.1 overexpression decreased food intake by approximately one-third. This study comprehensively describes the expression and function of eleven zebrafish

  2. Current stabilizer

    International Nuclear Information System (INIS)

    A current stabilizer for supplying magnetic lens of β-monochromator at the electron energy up to 1 MeV is described. Stabilization method with use of reference high-stabilized source of direct voltage with switching-in loading (monochromator coil) to circuit of negative feedback of direct-current amplifier with high gain is chosen for stabilization of direct current. The range of current regulation is 0.5 A at available power up to 15 W. Current instability during 10 hour continuous work does not exceed 10-4% that makes it possible to provide instability of electron energy at the monochromator exit using 90Sr+90Y β-nucleide of not more than 10 -4% and number of electrons 2.5x10-4% respectively

  3. Apolipoprotein B of low-density lipoprotein impairs nitric oxide-mediated endothelium-dependent relaxation in rat mesenteric arteries

    DEFF Research Database (Denmark)

    Zhang, Yaping; Zhang, Wei; Edvinsson, Lars; Xu, Cang-Bao

    2014-01-01

    Apolipoprotein B (ApoB) of low-density lipoprotein (LDL) causes endothelial dysfunction in the initial stage of atherogenesis. The present study was designed to explore the underlying molecular mechanisms involved. Rat mesenteric arteries were organ cultured in the presence of different concentra......Apolipoprotein B (ApoB) of low-density lipoprotein (LDL) causes endothelial dysfunction in the initial stage of atherogenesis. The present study was designed to explore the underlying molecular mechanisms involved. Rat mesenteric arteries were organ cultured in the presence of different...... concentrations of ApoB or LDL. Vasodilation induced by acetylcholine was monitored by a sensitive myograph. Nitric oxide (NO), endothelium-dependent hyperpolarizing factor (EDHF) and prostacyclin (PGI2) pathways were characterized by using specific pathway inhibitors. Real-time PCR and immunohistochemistry with......-dependently attenuated the endothelium-dependent vasodilation. Immunohistochemistry staining of endothelial cell marker CD31 was weaker in the presence of LDL, indicating that LDL induced damage to the endothelium. Using the pathway specific inhibitors demonstrated that LDL-induced impairing vasodilation was mainly due...

  4. Reduction of Risk Factor Coagulation Oxidative Apolipoprotein and Development of Atherosclerosis by Apple Cider Vinegar in Hypercholesterolemic Rabbits

    Directory of Open Access Journals (Sweden)

    Mahbubeh Setorki

    2009-01-01

    Full Text Available Introduction: Apple cider vinegar is an antioxidant compound and it has many medical uses. In this research we have investigated effects of apple cider vinegar on some risk factors of atherosclerosis and on the development of atherosclerosis in hypercholesterolemic rabbit. Methods: Thirty two male New Zealand rabbits were randomly divided into four groups: normal diet group high cholesterol diet group (%1cholesterol %1 cholesterol with 5ml apple cider vinegar group and %1 cholesterol with 10ml apple cider vinegar group .The malondialdehyde (MDA oxidized-LDL (oxLDL fibrinogen factor VII apolipoprotein A (ApoA and apolipoprotein B (ApoB were measured before the experiment and at the end period (2month. At the end of study using Chekanov method fatty streak formation in aorta artery was determined in all groups. Results: Using both doses of apple cider vinegar significantly decreased fibrinogen oxLDL MDA ApoB ApoB/ApoA VIIlevels in comparison with hypercholesterolemic diet (P0.05. Also consumption of apple cider vinegar induced significant decrease in atherosclerotic lesions in aorta artery compared to the hypercholesterolemic diet. Conclusion: This study suggests that apple cider vinegar (as an antioxidant might have some protective effects on biochemical risk factors of atherosclerosis.

  5. PARALLEL STABILIZATION

    Institute of Scientific and Technical Information of China (English)

    J.L.LIONS

    1999-01-01

    A new algorithm for the stabilization of (possibly turbulent, chaotic) distributed systems, governed by linear or non linear systems of equations is presented. The SPA (Stabilization Parallel Algorithm) is based on a systematic parallel decomposition of the problem (related to arbitrarily overlapping decomposition of domains) and on a penalty argument. SPA is presented here for the case of linear parabolic equations: with distrjbuted or boundary control. It extends to practically all linear and non linear evolution equations, as it will be presented in several other publications.

  6. Apolipoprotein B synthesis in rat small intestine: regulation by dietary triglyceride and biliary lipid

    International Nuclear Information System (INIS)

    Apolipoprotein B (apoB) synthesis rates have been determined, in vivo, in rat enterocytes. Following intralumenal administration of a pulse of [3H]leucine, newly synthesized apoB was quantitated by specific immunoprecipitation and compared to [3H]leucine incorporation into total, trichloroacetic acid-insoluble protein. ApoB synthesis rates were determined after acute administration of either 0.1 or 1 g of triglyceride to fasting animals. No differences were found at any time from 90 min to 6 hr after challenge and values were not different from the basal values established in fasted controls. Animals rechallenged with triglyceride after 8 days' intake of fat-free chow also failed to demonstrate a change in intestinal apoB synthesis rate. By contrast, enterocyte content of apoB appeared to fall, temporarily, with the onset of active triglyceride flux. Groups of animals were then subjected to external bile diversion for 48 hr, a maneuver designed to remove all lumenal sources of lipid. Jejunal apoB synthesis rates fell by 43% (from 0.76% +/- 0.14 to 0.43% +/- 0.12, P less than 0.001), a change that was completely prevented by continuous replacement with 10 mM Na taurocholate. The suppression of jejunal apoB synthesis, induced by prolonged bile diversion, was reversed after 14 hr, but not 8 hr, of intralumenal perfusion with 10 mM Na taurocholate. The addition of micellar fatty acid-monoolein to the perfusate for 4 hr produced no further change in apoB synthesis. Ileal apoB synthesis rates fell by 70% (from 0.61% +/- 0.15 to 0.18% +/- 0.10, P less than 0.001) following 48 hr external bile diversion, a change that was only partially prevented by continuous bile salt replacement. These results suggest that jejunal apoB synthesis demonstrates bile salt dependence but not regulation by acute triglyceride flux

  7. Apolipoprotein E isoform-dependent dendritic recovery of hippocampal neurons following activation of innate immunity

    Directory of Open Access Journals (Sweden)

    Maezawa Izumi

    2006-08-01

    Full Text Available Abstract Background Innate immune activation, including a role for cluster of differentiation 14/toll-like receptor 4 co-receptors (CD14/TLR-4 co-receptors, has been implicated in paracrine damage to neurons in several neurodegenerative diseases that also display stratification of risk or clinical outcome with the common alleles of the apolipoprotein E gene (APOE: APOE2, APOE3, and APOE4. Previously, we have shown that specific stimulation of CD14/TLR-4 with lipopolysaccharide (LPS leads to greatest innate immune response by primary microglial cultures from targeted replacement (TR APOE4 mice and greatest p38MAPK-dependent paracrine damage to neurons in mixed primary cultures and hippocampal slice cultures derived from TR APOE4 mice. In contrast, TR APOE2 astrocytes had the highest NF-kappaB activity and no neurotoxicity. Here we tested the hypothesis that direct activation of CD14/TLR-4 in vivo would yield different amounts of paracrine damage to hippocampal sector CA1 pyramidal neurons in TR APOE mice. Methods We measured in vivo changes in dendrite length in hippocampal CA1 neurons using Golgi staining and determined hippocampal apoE levels by Western blot. Neurite outgrowth of cultured primary neurons in response to astrocyte conditioned medium was assessed by measuring neuron length and branch number. Results Our results showed that TR APOE4 mice had slightly but significantly shorter dendrites at 6 weeks of age. Following exposure to intracerebroventricular LPS, there was comparable loss of dendrite length at 24 hr among the three TR APOE mice. Recovery of dendrite length over the next 48 hr was greater in TR APOE2 than TR APOE3 mice, while TR APOE4 mice had failure of dendrite regeneration. Cell culture experiments indicated that the enhanced neurotrophic effect of TR APOE2 was LDL related protein-dependent. Conclusion The data indicate that the environment within TR APOE2 mouse hippocampus was most supportive of dendrite regeneration

  8. Plasma level and genetic variation of apolipoprotein E in patients with lipoprotein glomerulopathy

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bo; LIU Zhi-hong; ZENG Cai-hong; ZHENG Jing-min; CHEN Hui-ping; ZHOU Hong; LI Lei-shi

    2005-01-01

    Background Lipoprotein glomerulopathy (LPG) is a renal disease characterized by thrombus-like lipoproteins in the glomerular capillaries and its abnormal lipoprotein profiles with marked elevation of apolipoprotein E (apoE). In this study, 15 Chinese patients with LPG were involed in exploring the association of the genetic variation and its plasma level in the pathogenesis of LPG.Methods A retrospective analysis of the clinical and pathological features was made in 15 patients with LPG. Plasma concentrations of apoE were measured with radial immunodiffusion assay. Genetic variations of apoE gene were detected using polymerase chain reaction and restriction fragment length polymorphism. Glomerular deposition of apoA, apoB and apoE in these patients were detected by immunofluorescence staining using monoclonal antibodies. Results Biochemical profiles of lipids and lipoproteins revealed markedly elevated levels of triglyceride, apoB and apoE, but approximately normal levels of total cholesterol, apoA1 and lipoprotein(a) [Lp(a)], which resembled familial hypertriglyceridemia. Genetic analysis demonstrated that the genotype distribution of apoE were 7 cases with ε3/ε 4, 4 cases with ε3/ε 3 and 2 cases with ε2/ε 3. The other 2 cases (a mother and her son) showed a same distinct band. The band pattern of later 2 cases was quite similar to the apoE variant of Tokyo type. The calculated allele frequency of ε 4 was relatively high in cases with LPG in comparison with that in the normal controls. We further divided the 13 patients into three groups according to their genotypes of apoE. Patients with the genotype of apoE ε2/ε3 showed a lower level of plasma apoE as compared to those with apoE ε3/ε4 (P<0.05). The serum level of high-density lipoprotein (HDL) was the lowest in patients with the genotype of apoE ε3/ε4. No difference was found among the patients with different apoE genotype in the other clinical and pathological characteristics. Conclusions The

  9. Apolipoprotein E COG 133 mimetic peptide improves 5-fluorouracil-induced intestinal mucositis

    Directory of Open Access Journals (Sweden)

    Azevedo Orleâncio Gomes R

    2012-07-01

    Full Text Available Abstract Background Intestinal mucositis is one of the major troublesome side effects of anticancer chemotherapy leading to poor patient compliance. In this study we addressed the role of the novel apolipoprotein E (ApoE COG 133 mimetic peptide in 5-fluorouracil (5-FU-challenged Swiss mice and IEC-6 cell monolayers. Experiments were also conducted in C57BL6J ApoE knock-out mice to assess the effects of apoE peptide treatment. Methods Experimental groups were as follows: unchallenged controls, 5-FU-challenged mice (450 mg/kg, i.p with or without the ApoE peptide (0.3, 1, and 3 μM, given twice daily i.p. for 4 days. Mice were sacrificed 3 days after 5-FU challenge. Proximal small intestinal samples were harvested for molecular biology and histological processing. We conducted ELISA assays and RT-PCR to target IL-1β, TNF-α, IL-10, iNOS, and myeloperoxidase (MPO to assess intestinal inflammation. Cell death and NF-κB assays were also conducted in apoE knock-out mice. In our in vitro models, IEC-6 cells were exposed to 1 mM of 5-FU in glutamine free media with or without the ApoE peptide (0.02, 0.2, 2, 5, 10, and 20 μM. We investigated IEC-6 cell proliferation and migration, 24 h after the 5-FU challenge. Additionally, apoptotic IEC-6 cells were measured by Tunel and flow cytometry. Equimolar doses of the ApoA-I (D4-F peptide were also used in some experiments for comparative studies. Results Villus blunting and heavy inflammatory infiltrates were seen in the 5-FU-challenged group, findings that were partially ameliorated by the ApoE peptide. We found increased intestinal MPO and pro-inflammatory IL-1β and TNF-α levels, and TNF-α and iNOS transcripts, and reduction of IL-10 following 5-FU treatment, each of which were partially abrogated by the peptide. Improvements were also found in IEC-6 cell apoptosis and migration following ApoE and D-4F treatment. Conclusion Altogether, these findings suggest that the novel ApoE COG 133 mimetic peptide

  10. Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Araújo, C.V. [Laboratório da Biologia da Cicatrização, Ontogenia e Nutrição de Tecidos, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Lazzarotto, C.R. [Laboratório de Biologia Molecular e do Desenvolvimento, Universidade de Fortaleza, Fortaleza, CE (Brazil); Aquino, C.C.; Figueiredo, I.L.; Costa, T.B.; Oliveira Alves, L.A. de [Laboratório da Biologia da Cicatrização, Ontogenia e Nutrição de Tecidos, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Ribeiro, R.A. [Laboratório da Inflamação e Câncer, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Bertolini, L.R. [Laboratório de Biologia Molecular e do Desenvolvimento, Universidade de Fortaleza, Fortaleza, CE (Brazil); Lima, A.A.M. [Laboratório de Doenças Infecciosas, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Brito, G.A.C. [Laboratório da Inflamação e Câncer, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Oriá, R.B. [Laboratório da Biologia da Cicatrização, Ontogenia e Nutrição de Tecidos, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil)

    2015-04-28

    Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE{sup -/-}) and wild-type (APOE{sup +/+}) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE{sup -/-} mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE{sup +/+} mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE{sup -/-}-challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU

  11. Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

    Directory of Open Access Journals (Sweden)

    C.V. Araújo

    2015-06-01

    Full Text Available Apolipoprotein E (APOE=gene, apoE=protein is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/- and wild-type (APOE+/+ C57BL6J male and female mice (N=86 were given either Ala-Gln (100 mM or phosphate buffered saline (PBS by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU challenge (450 mg/kg, via intraperitoneal injection. Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1 and B-cell lymphoma 2 (Bcl-2 intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001 in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05 were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/--challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge.

  12. Apolipoprotein E gene polymorphism and total serum cholesterol level in Iranian population

    Directory of Open Access Journals (Sweden)

    Bazzaz J

    2010-01-01

    Full Text Available Background: Apolipoprotein E (APOE is known as a major regulator of blood lipid levels in humans. A number of APOE gene allelic variants have been reported including E2, E3 and E4. Recent studies suggested a role for APOE in obesity and increased Body Mass Index (BMI and plasma lipid levels in obese children. Aim: The aim of this study was to examine the association between APOE genetic variants and the BMI and lipid profile in an Iranian cohort. Setting and Design: Samples were obtained from subjects who participated in a study based on the WHO-designed MONICA (multinational monitoring of trends and determinants in cardiovascular disease study for coronary artery disease risk assessment in Zone 17 of Tehran. The study was approved by the local ethical committee. Informed consent was obtained from all subjects included in this study. Materials and Methods: Subjects (n=320 were recruited. The level of triglyceride (TG and total serum cholesterol was tested for all subjects in this study. Genotyping for APOE was carried using polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLPtechnique. Statistical Analysis: Levels of significance were determined using contingency tables by either Chi-square or Fisher exact analysis using the STATA (v8 software. The analysis of regression and significance of differences for level of cholesterol and TG was established by one-way analysis of variance followed by Dunnett post hoc multiple comparison tests using SPSS software Version 11.5. Results: The frequency of allele E2 was significantly higher in patients with total serum cholesterol level <200 mg/dl (P 0.01 OR 2.1 95% CI 1.1-4.2. Conclusion: The association found in this study between allele E2 and lower total cholesterol level had been reported in previous studies. We have also observed that the frequency of genotype E2/E3 and E2/E4 was significantly higher in patients with normal total serum cholesterol level compared to patients with

  13. Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

    International Nuclear Information System (INIS)

    Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/-) and wild-type (APOE+/+) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/--challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge

  14. Apolipoprotein E gene polymorphisms are associated with primary hyperuricemia in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Jie Wu

    Full Text Available OBJECTIVE: Primary hyperuricemia, an excess of uric acid in the blood, is a major public health problem. In addition to the morbidity that is attributable to gout, hyperuricemia is also associated with metabolic syndrome, hypertension, and cardiovascular disease. This study aims to assess the genetic associations between Apolipoprotein E (APOE polymorphisms and hyperuricemia in a Chinese population. METHODS: A total of 770 subjects (356 hyperuricemic cases and 414 normouricemic controls were recruited from the Ningxia Hui Autonomous Region, China. A physical examination was performed and fasting blood was collected for biochemical tests, including determination of the levels of serum lipid, creatinine, and uric acid. Multi-ARMS PCR was applied to determine the APOE genotypes, followed by an investigation of the distribution of APOE genotypes and alleles frequencies in the controls and cases. RESULTS: The frequencies of the APOE-ε2ε3 genotype (17.70% vs. 10.39%, P = 0.003 and the APOE-ε2 allele (10.53% vs. 5.80%, P = 0.001 were significantly higher in the hyperuricemic group than in the normouricemic group. Furthermore, male cases were more likely to have the APOE-ε2ε3 genotype and APOE-ε2 allele, compared with male controls. In both Han and Hui subjects, cases were more likely to have the APOE-ε2ε3 genotype and the APOE-ε2 allele compared with controls. Furthermore, multivariate logistic regression showed that carriers of the APOE-ε2ε3 genotype (P = 0.001, OR = 2.194 and the ε2 allele (P = 0.001, OR = 2.099 were significantly more likely to experience hyperuricemia than carriers of the ε3/ε3 genotype and the ε3 allele after adjustment for sex, body mass index (BMI, diastolic blood pressure (DBP, triglyceride (TG, low density lipoprotein cholesterol (LDL-C, creatinine (Cr and fasting blood glucose (FBG. CONCLUSIONS: The APOE-ε2ε3 genotype and the APOE-ε2 allele are associated with serum uric acid levels

  15. The role of apolipoprotein A-IV in regulating glucagon-like peptide-1 secretion.

    Science.gov (United States)

    Wang, Fei; Yang, Qing; Huesman, Sarah; Xu, Min; Li, Xiaoming; Lou, Danwen; Woods, Stephen C; Marziano, Corina; Tso, Patrick

    2015-10-15

    Both glucagon-like peptide-1 (GLP-1) and apolipoprotein A-IV (apoA-IV) are produced from the gut and enhance postprandial insulin secretion. This study investigated whether apoA-IV regulates nutrient-induced GLP-1 secretion and whether apoA-IV knockout causes compensatory GLP-1 release. Using lymph-fistula-mice, we first determined lymphatic GLP-1 secretion by administering apoA-IV before an intraduodenal Ensure infusion. apoA-IV changed neither basal nor Ensure-induced GLP-1 secretion relative to saline administration. We then assessed GLP-1 in apoA-IV-/- and wild-type (WT) mice administered intraduodenal Ensure. apoA-IV-/- mice had comparable lymph flow, lymphatic triglyceride, glucose, and protein outputs as WT mice. Intriguingly, apoA-IV-/- mice had higher lymphatic GLP-1 concentration and output than WT mice 30 min after Ensure administration. Increased GLP-1 was also observed in plasma of apoA-IV-/- mice at 30 min. apoA-IV-/- mice had comparable total gut GLP-1 content relative to WT mice under fasting, but a lower GLP-1 content 30 min after Ensure administration, suggesting that more GLP-1 was secreted. Moreover, an injection of apoA-IV protein did not reverse the increased GLP-1 secretion in apoA-IV-/- mice. Finally, we assessed gene expression of GLUT-2 and the lipid receptors, including G protein-coupled receptor (GPR) 40, GPR119, and GPR120 in intestinal segments. GLUT-2, GPR40 and GPR120 mRNAs were unaltered by apoA-IV knockout. However, ileal GPR119 mRNA was significantly increased in apoA-IV-/- mice. GPR119 colocalizes with GLP-1 in ileum and stimulates GLP-1 secretion by sensing OEA, lysophosphatidylcholine, and 2-monoacylglycerols. We suggest that increased ileal GPR119 is a potential mechanism by which GLP-1 secretion is enhanced in apoA-IV-/- mice. PMID:26294669

  16. Mechanisms of cinnamon extract-induced suppression of the intestinal overproduction of apolipoprotein B48-containing lipoproteins in insulin resistant high-fructose fed animals

    Science.gov (United States)

    We have reported previously that cinnamon extract (CE) prevents high-fructose (HF) feeding-induced whole-body insulin resistance by enhancing insulin signaling in skeletal muscle. In this study, we investigated whether intestinal apolipoprotein overproduction is inhibited by CE in this insulin-resis...

  17. Characterization of High Density Lipoprotein Particles in Familial Apolipoprotein A-I Deficiency With Premature Coronary Atherosclerosis, Corneal Arcus and Opacification, and Tubo-Eruptive and Planar Xanthomas

    Science.gov (United States)

    We describe two male siblings with homozygous familial apolipoprotein (apo) A-I deficiency, markedly decreased high density lipoprotein (HDL) cholesterol levels, undetectable plasma apoA-1, tubo-eruptive and planar xanthomas, and mild corneal arcus and opacification. Sequencing of the apoA-I gene re...

  18. Proteomic and meatbolomic analysis of smooth muscle cells derived from the arterial media and adventitial progenitors of apolipoprotein E-deficient mice

    NARCIS (Netherlands)

    Mayr, M; Zampetaki, A.; Sidibe, A.; Mayr, U.; Yin, X.; Souza, A.I. de; Chung, Y.L.; Madhu, B.; Quax, P.H.; Hu, Y.; Griffiths, J.R.; Xu, Q.

    2008-01-01

    We have recently demonstrated that stem cell antigen 1-positive (Sca-1(+)) progenitors exist in the vascular adventitia of apolipoprotein E-deficient (apoE(-/-)) mice and contribute to smooth muscle cell (SMC) accumulation in vein graft atherosclerosis. Using a combined proteomic and metabolomic app

  19. RELATIONSHIP BETWEEN LIVER FAT CONTENT AND THE RATE OF VLDL APOLIPOPROTEIN B-100 SYNTHESIS IN CHILDREN WITH PROTEIN-ENERGY MALNUTRITION

    Science.gov (United States)

    Fatty infiltration of the liver is associated with an increased morbidity and mortality in children with severe protein-energy malnutrition (PEM), but its pathogenesis remains unclear. Although impaired synthesis of VLDL apolipoprotein B-100 (VLDL-apo B-100) is generally accepted as the pathogenetic...

  20. The Influence of the Epsilon4 Allele of the Apolipoprotein E Gene on Childhood IQ, Nonverbal Reasoning in Old Age, and Lifetime Cognitive Change.

    Science.gov (United States)

    Deary, Ian J.; Whalley, Lawrence J.; St. Clair, David; Breen, Gerome; Leaper, Steve; Lemmon, Helen; Hayward, Caroline; Starr, John M.

    2003-01-01

    Examines the influence of apolipoprotein E gene states on three cognitive outcomes in 173 people at age 11 and in the same people at age 77 and examined the change in IQ between these ages. There was no significant main effect of gene status on IQ in youth or old age, nor in cognitive change across the lifespan. (SLD)

  1. Macroeconomic stability

    DEFF Research Database (Denmark)

    Jespersen, Jesper

    2004-01-01

    It is demonstrated that full employment and sustainable development not necessarily are conflicting goals. On the other hand macroeconomic stability cannot be obtained without a deliberate labour sharing policy and a shift in the composition of private consumption away from traditional material...

  2. Isolation, characterization, and stability of discretely-sized nanolipoprotein particles assembled with apolipophorin-III.

    Directory of Open Access Journals (Sweden)

    Nicholas O Fischer

    Full Text Available BACKGROUND: Nanolipoprotein particles (NLPs are discoidal, nanometer-sized particles comprised of self-assembled phospholipid membranes and apolipoproteins. NLPs assembled with human apolipoproteins have been used for myriad biotechnology applications, including membrane protein solubilization, drug delivery, and diagnostic imaging. To expand the repertoire of lipoproteins for these applications, insect apolipophorin-III (apoLp-III was evaluated for the ability to form discretely-sized, homogeneous, and stable NLPs. METHODOLOGY: Four NLP populations distinct with regards to particle diameters (ranging in size from 10 nm to >25 nm and lipid-to-apoLp-III ratios were readily isolated to high purity by size exclusion chromatography. Remodeling of the purified NLP species over time at 4 degrees C was monitored by native gel electrophoresis, size exclusion chromatography, and atomic force microscopy. Purified 20 nm NLPs displayed no remodeling and remained stable for over 1 year. Purified NLPs with 10 nm and 15 nm diameters ultimately remodeled into 20 nm NLPs over a period of months. Intra-particle chemical cross-linking of apoLp-III stabilized NLPs of all sizes. CONCLUSIONS: ApoLp-III-based NLPs can be readily prepared, purified, characterized, and stabilized, suggesting their utility for biotechnological applications.

  3. Expression of human apolipoprotein A-I in transgenic mice results in reduced plasma levels of murine apolipoprotein A-I and the appearance of two new high density lipoprotein size subclasses

    International Nuclear Information System (INIS)

    In Western societies high density lipoprotein (HDL) levels correlate inversely with the risk for coronary heart disease. The primary protein component of both human and mouse HDL is apolipoprotein A-I (apoAI), which comprises >70% of HDL protein and 30% of HDL mass. Human HDLs include particles of several distinct size subpopulations, wheras HDLs from inbred C57BL/6 mice contain a single population of particles. To study the regulation of apoAI expression and its role in HDL assembly, we created transgenic C57BL/6 mice containing the human apoAI gene. Two independent lines of transgenic mice with approximately twice the normal plasma levels of total apoAI were studied. The level of mouse apoAI is reduced >4-fold in both transgenic lines, comprising only 4% of total plasma apoAI levels in one transgenic line and 13% in the other. The authors demonstrate that the mechanism responsible for the decrease in mouse apoAI is posttranscriptional. Parallel to the replacement of mouse with human apoAI, the single HDL species normally present in the plasma of C57BL/6 is replaced by two HDL subclasses similar in size to human HDL2b and HDL3a. The changes in murine apolipoprotein levels and HDL subclass size are inherited by all transgenic offspring of the two founder animals. These results suggest a dominant role of apoAI in determining the HDL particle size distribution and a mechanism involving expression of human apoAI transgenes that alters the plasma levels of mouse apoAI

  4. Frequency stability

    Czech Academy of Sciences Publication Activity Database

    Kroupa, Věnceslav František

    Bratislava: Department of Radio and Electronics, FEI STU, 2006 - (Píš, P.; Krajčušková, Z.), I.1-I.9 ISBN 80-227-2388-6. [ Radio elektronika 2006. Conference proceedings. Bratislava (SK), 25.04.2006-26.04.2006] R&D Projects: GA ČR(CZ) GA102/05/0852 Institutional research plan: CEZ:AV0Z20670512 Keywords : noise * frequency stability * frequency control Subject RIV: JW - Navigation, Links, Detection ; Counter-Measures

  5. Apolipoprotein B-containing lipoprotein particle assembly: Lipid capacity of the nascent lipoprotein particle

    Energy Technology Data Exchange (ETDEWEB)

    Manchekar, Medha; Forte, Trudy M.; Datta, Geeta; Richardson, Paul E.; Segrest, Jere P.; Dashti, Nassrin

    2003-12-01

    We previously proposed that the N-terminal 1000 residue {beta}{alpha}{sub 1} domain of apolipoprotein B (apoB) forms a bulk lipid pocket homologous to that of lamprey lipovitellin (LV). In support of this ''lipid pocket'' hypothesis, apoB:1000 (residues 1-1000) was shown to be secreted by a stable transformant of McA-RH7777 cells as a monodisperse particle with HDL{sub 3} density and Stokes diameter of 112 {angstrom}. In contrast, apoB:931 (residues 1-931), missing only 69 residues of the sequence homologous to LV, was secreted as a particle considerably more dense than HDL with Stokes diameter of 110 {angstrom}. The purpose of the present study was to determine the stoichiometry of the lipid component of the apoB:931 and apoB:1000 particles. This was accomplished by metabolic labeling of cells with either [{sup 14}C]oleic acid or [{sup 3}H]glycerol followed by immunoprecipitation (IP) or nondenaturing gradient gel electrophoresis (NDGGE) of secreted lipoproteins and by immunoaffinity chromatography of secreted unlabeled lipoproteins. The [{sup 3}H]-labeled apoB:1000-containing particles, isolated by NDGGE, contained 50 phospholipids (PL) and 11 triacylglycerols (TAG) molecules per particle. In contrast, apoB:931-containing particles contained only a few molecules of PL and were devoid of TAG. The unlabeled apoB:1000-containing particles isolated by immunoaffinity chromatography and analyzed for lipid mass, contained 56 PL, 8 TAG, and 7 cholesteryl ester molecules per particle. The surface:core lipid ratio of apoB:1000-containing particles was approximately 4:1 and was not affected by incubation of cells with oleate. Although small amounts of microsomal triglyceride transfer protein (MTP) were associated with apoB:1000-containing particles, it never approached a 1:1 molar ratio of MTP to apoB. These results support a model in which: (1) the first 1000 amino acid residues of apoB are competent to complete the ''lipid pocket

  6. Hydrogen sulfide regulates vascular endoplasmic reticulum stress in apolipoprotein E knockout mice

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhi-fang; ZHAO Bin; TANG Xiu-ying; LI Wei; ZHU Lu-lu; TANG Chao-shu; DU Jun-bao; JIN Hong-fang

    2011-01-01

    Background Atherosclerosis is an important cardiovascular disease,becoming a major and increasing health problem in developed countries.However,the possible underlying mechanisms were not completely clear.In 2009,our research group first discovered that hydrogen sulfide (H2S) as a novel gastrotransmitter played an important anti-atherosclerotic role.The study was designed to examine the regulatory effect of hydrogen sulfide (H2S) on endoplasmic reticulum stress (ERS) in apolipoprotein E knockout (apoE(-/-)) mice fed a Western type diet.Methods C57BL/6 mice and homozygous apoE(-/-) mice were fed a Western type diet.C57BL/6 mice were injected intraperitoneally with normal saline (5 ml/kg per day) as control group.The apoE+ mice were treated with the same dose of normal saline as the apoE(-/-) group,injected intraperitoneally with sodium hydrosulfide (NaHS,an H2S donor,56μmol/kg per day) as the apoE(-/-)+NaHS group and injected intraperitoneally with DL-propargylglycine (PPG,a cystathionine-y-lyase inhibitor,50 mg/kg,per day) as the apoE/ +PPG group.After 10 weeks,the mice were sacrificed and the plasma lipids were detected.Sections of aortic root from these animals were examined for atherosclerotic lesions by HE and oil red O staining.The aortic ultrastructure and microstructure were analyzed with the help of light and electronic microscope.Glucose-regulated protein 78 (GRP78),caspase-12,copper-andzinc-containing superoxide dismutase (Cu/ZnSOD) and Mn-containing superoxide dismutase (MnSOD) protein expression in aortic tissues were detected with immunohistochemistry.The level of intracellular reactive oxygen species (ROS) were measured by using a commercial assay kit.Results Compared with control mice,apoE(-/-) mice showed increased plasma levels of total cholesterol (TC),triglyceride (TG) and low density lipoprotein (LDL),decreased high density lipoprotein (HDL),increased aortic plaque size,destroyed ultra-structure of aortic tissue,and increased expression of GRP

  7. Characterization of apolipoprotein B-containing lipoproteins separated by preparative free flow isotachophoresis.

    Science.gov (United States)

    Nowicka, G; Brüning, T; Grothaus, B; Kahl, G; Schmitz, G

    1990-07-01

    Preparative free flow isotachophoresis (ITP) was used for the fractionation of apoB-containing lipoproteins (d less than 1.063 g/ml) from fasting and postprandial sera derived from normolipidemic individuals. According to their net electric mobility, four major particle groups (I-IV) have been recognized. The fast-migrating particles in group I, which correspond predominantly to very low density lipoproteins (VLDL), are rich in triglycerides, free cholesterol, phosphatidylcholine, and apoE and C apolipoproteins. This group expresses nonspecific binding to fibroblasts but binds to HepG2 cells with high affinity (KD = 3.6 micrograms/ml, Bmax = 37 ng) to a single class of binding sites. The particles migrating in group II, which are related to intermediate density lipoproteins (IDL), are richer in cholesteryl esters and apoB than those in group I. They interact specifically with a single site on fibroblasts (KD = 7.8 micrograms/ml, Bmax = 54 ng) while on HepG2 cells two binding sites, one with a higher (KD = 3.5 micrograms/ml, Bmax = 22 ng) and one with a lower affinity component (KD = 16.9 micrograms/ml, Bmax = 53 ng), are involved. The particles migrating in groups III and IV correspond to low density lipoproteins (LDL). The protein moiety of both fractions consists almost exclusively of apoB. Group III represents cholesteryl ester-rich LDL particles, while the particles in group IV contain smaller amounts of cholesteryl esters. The lipoproteins of both groups are ligands for apoB,E-receptors. However, the particles in group IV interact with fibroblasts with the highest affinity (KD = 2.3 micrograms/ml, Bmax = 58 ng) and with the biphasic HepG2 cell binding sites with the lowest affinity of all analyzed groups (KD1 = 11.2 micrograms/ml, Bmax1 = 58 ng, KD2 = 68 micrograms/ml, Bmax2 = 170 ng). When apoB-containing lipoproteins were isolated from postprandial sera of the same individuals, significant changes in the lipid composition were observed only in particle

  8. High-salt diet combined with elevated angiotensin II accelerates atherosclerosis in apolipoprotein E-deficient mice

    DEFF Research Database (Denmark)

    Johansson, Maria E; Bernberg, Evelina; Andersson, Irene J; Bie, Peter; Skøtt, Ole; Gan, Li-ming; Bergström, Göran

    2009-01-01

    atherosclerosis. METHODS: Apolipoprotein E-deficient (ApoE-/-) mice received standard or high-salt diet (8%) alone or in combination with fixed angiotensin II (Ang II) infusion (0.5 microg/kg per min). BP was measured using telemetry, and plaque burden was assessed in the thoracic aorta and innominate artery. We......OBJECTIVES: High-salt diet likely elevates blood pressure (BP), thus increasing the risk of cardiovascular events. We hypothesized that a high-salt diet plays a critical role in subjects whose renin-angiotensin systems cannot adjust to variable salt intake, rendering them more susceptible to...... used urinary isoprostane as a marker for oxidative stress. RESULTS: Although high-salt diet per se did not affect plaque extension, high salt combined with Ang II increased plaque area significantly in both the aorta and the innominate artery as compared with Ang II or salt alone (P < 0.05 and P < 0...

  9. Influence of apolipoprotein E and its receptors on cerebral amyloid precursor protein metabolism following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    ZHOU Shuai; SUN Xiao-chuan

    2012-01-01

    Traumatic brain injury (TBI) is the leading cause of mortality and disability among young individuals in our society,and globally the incidence of TBI is rising sharply.Mounting evidence has indicated that apolipoprotein E (apoE:protein; APOE:gene) genotype influences the outcome after TBI.The proposed mechanism by which APOE affects the clinicopathological consequences of TBI is multifactorial and includes amyloid deposition,disruption of lipid distribution,dysfunction of mitochondrial energy production,oxidative stress and increases intracellular calcium in response to injury.This paper reviews the current state of knowledge regarding the influence of apoE and its receptors on cerebral amyloid betaprotein precursor metabolism following TBI.

  10. Cloning and Expression of Apolipoprotein E3 and Its Variant apoE2 and apoE4

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to obtain three isoforms of apolipoprotein E (apoE), the cDNA encoding apoE3 was obtained by RT-PCR from normal human liver tissue. Site-directed mutagenesis was used to obtain the cDNAs encoding apoE2 and apoE4 isoforms. The 3 cDNAs were subcloned into vector pGEM-3Z and verified by DNA sequencing. The expression recombinant which can express the target protein as a (His) 6-tagged fusion was constructed by subcloning apoE cDNA into vector pT7-PL. The purified proteins were gained by Ni-NTA column. The SDS-PAGE results revealed the 6 His fusion proteins (apoE2, apoE3 and apoE4) were correctly expressed and purified successfully.

  11. Enhanced synthesis and secretion of apolipoprotein E from sciatic nerves of streptozotocin-induced diabetic rats after injury

    International Nuclear Information System (INIS)

    To elucidate the pathogenesis of diabetic neuropathy, synthesis and secretion of apolipoprotein E (apo E) from sciatic nerves after injury was studied in normal and streptozotocin-induced diabetic rats. Seven, 14, 28, 45 and 59 days after making crush injury on sciatic nerves with concomitant administration of streptozotocin (50 mg/kg body weight), the nerves were taken out and incubated with [35S]methionine. The [35S]labeled apo E was precipitated with specific antiserum. The amounts of apo E secreted into medium by nerves of diabetic rats were 7 times greater than those of non-diabetic rats 7 days after injury. This enhanced secretion of apo E was relatively selective for this protein, since the ratio of the immunoprecipitable apo E to the TCA preciptitable protein in the medium increased in diabetic rats. Intriguing possibility deduced from these results is that the secretion of apo E is involved in the development of diabetic neuropathy

  12. Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipoprotein E knockout mice

    DEFF Research Database (Denmark)

    Bentzon, Jacob F; Sondergaard, Claus S; Kassem, Mustafa;

    2007-01-01

    circulating bone marrow-derived progenitor cells. Here, we analyzed the contribution of this mechanism to plaque healing after spontaneous and mechanical plaque disruption in apolipoprotein E knockout (apoE-/-) mice. METHODS AND RESULTS: To determine the origin of SMCs after spontaneous plaque disruption......GFP+ SMCs were detected. To examine the origin of healing SMCs in a model that recapitulates more features of human plaque rupture and healing, we developed a mechanical technique that produced consistent plaque disruption, superimposed thrombosis, and SMC-mediated plaque healing in apoE-/- mice. Mechanical...... originating from outside the local arterial segment were detected in healed plaques. CONCLUSIONS: Healing SMCs after atherosclerotic plaque disruption are derived entirely from the local arterial wall and not circulating progenitor cells in apoE-/- mice. Udgivelsesdato: 2007-Oct-30...

  13. High-salt diet combined with elevated angiotensin II accelerates atherosclerosis in apolipoprotein E-deficient mice

    DEFF Research Database (Denmark)

    Johansson, Maria E; Bernberg, Evelina; Andersson, Irene J;

    2009-01-01

    < 0.001 vs. Ang II alone). Ang II increases macrophage content in lesions (P < 0.05), whereas salt likely increases collagen content. CONCLUSION: High-salt diet per se does not influence BP in ApoE-/- mice and is only moderately atherogenic. Possibly mediated via increased oxidative stress, a high...... atherosclerosis. METHODS: Apolipoprotein E-deficient (ApoE-/-) mice received standard or high-salt diet (8%) alone or in combination with fixed angiotensin II (Ang II) infusion (0.5 microg/kg per min). BP was measured using telemetry, and plaque burden was assessed in the thoracic aorta and innominate artery. We...... used urinary isoprostane as a marker for oxidative stress. RESULTS: Although high-salt diet per se did not affect plaque extension, high salt combined with Ang II increased plaque area significantly in both the aorta and the innominate artery as compared with Ang II or salt alone (P < 0.05 and P < 0...

  14. Proteomic Profile of Unstable Atheroma Plaque: Increased Neutrophil Defensin 1, Clusterin, and Apolipoprotein E Levels in Carotid Secretome.

    Science.gov (United States)

    Aragonès, Gemma; Auguet, Teresa; Guiu-Jurado, Esther; Berlanga, Alba; Curriu, Marta; Martinez, Salomé; Alibalic, Ajla; Aguilar, Carmen; Hernández, Esteban; Camara, María-Luisa; Canela, Núria; Herrero, Pol; Ruyra, Xavier; Martín-Paredero, Vicente; Richart, Cristóbal

    2016-03-01

    Because of the clinical significance of carotid atherosclerosis, the search for novel biomarkers has become a priority. The aim of the present study was to compare the protein secretion profile of the carotid atherosclerotic plaque (CAP, n = 12) and nonatherosclerotic mammary artery (MA, n = 10) secretomes. We used a nontargeted proteomic approach that incorporated tandem immunoaffinity depletion, iTRAQ labeling, and nanoflow liquid chromatography coupled to high-resolution mass spectrometry. In total, 162 proteins were quantified, of which 25 showed statistically significant differences in secretome levels between carotid atherosclerotic plaque and nondiseased mammary artery. We found increased levels of neutrophil defensin 1, apolipoprotein E, clusterin, and zinc-alpha-2-glycoprotein in CAP secretomes. Results were validated by ELISA assays. Also, differentially secreted proteins are involved in pathways such as focal adhesion and leukocyte transendothelial migration. In conclusion, this study provides a subset of identified proteins that are differently expressed in secretomes of clinical significance. PMID:26795031

  15. The Immune-Modulatory Role of Apolipoprotein E with Emphasis on Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Hong-Liang Zhang

    2010-01-01

    Full Text Available Apolipoprotein E (apoE is a 34.2 kDa glycoprotein characterized by its wide tissue distribution and multiple functions. The nonlipid-related properties of apoE include modulating inflammation and oxidation, suppressing T cell proliferation, regulating macrophage functions, and facilitating lipid antigen presentation by CD1 molecules to natural killer T (NKT cells, and so forth. Increasing studies have revealed that APOE ε allele might be associated with multiple sclerosis (MS, although evidence is still not sufficient enough. In this review, we summarized the current progress of the immunomodulatory functions of apoE, with special focus on the association of APOE ε allele with the clinical features of MS and of its animal model experimental autoimmune encephalomyelitis (EAE.

  16. Recombinant Neural Protein PrP Can Bind with Both Recombinant and Native Apolipoprotein E In Vitro

    Institute of Scientific and Technical Information of China (English)

    Chen GAO; Wei ZHOU; Xiao-Ping DONG; Yan-Jun LEI; Jun HAN; Qi SHI; Lan CHEN; Yan GUO; Yong-Jun GAO; Jian-Ming CHEN; Hui-Ying JIANG

    2006-01-01

    The most essential and crucial step during the pathogenesis of transmissible spongiform encephalopathy is the conformational change of cellular prion protein (PrPC) to pathologic isoform (prpSc). A lot of data revealed that caveolae-like domains (CLDs) in the cell surface were the probable place where the conversion of PrP proteins happened. Apolipoprotein E (ApoE) is an apolipoprotein which is considered to play an important role in the development of Alzheimer's disease and other neurodegenerative diseases by forming protein complex through binding to the receptor located in the clathrin-coated pits of the cell surface.In this study, a 914-bp cDNA sequence encoding human ApoE3 was amplified from neuroblastoma cell line SH-SY5Y. Three human ApoE isomers were expressed and purified from Escherichia coli. ApoE-specific antiserum was prepared by immunizing rabbits with the purified ApoE3. GST/His pull-down assay,immunoprecipitation and ELISA revealed that three full-length ApoE isomers interact with the recombinant full-length PrP protein in vitro. The regions corresponding to protein binding were mapped in the N-terminal segment of ApoE (amino acid 1-194) and the N-terminal of PrP (amino acid 23-90). Moreover, the recombinant PrP showed the ability to form a complex with the native ApoE from liver tissues. Our data provided direct evidence of molecular interaction between ApoE and PrP. It also supplied scientific clues for assessing the significance of CLDs on the surface of cellular membrane in the process of conformational conversion from PrPC to PrPSc and probing into the pathogenesis of transmissible spongiform encephalopathy.

  17. Effect of TNF{alpha} on activities of different promoters of human apolipoprotein A-I gene

    Energy Technology Data Exchange (ETDEWEB)

    Orlov, Sergey V., E-mail: serge@iem.sp.ru [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Mogilenko, Denis A. [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Shavva, Vladimir S. [Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Dizhe, Ella B.; Ignatovich, Irina A. [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Perevozchikov, Andrej P., E-mail: app@iem.sp.ru [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation)

    2010-07-23

    Research highlights: {yields} TNF{alpha} stimulates the distal alternative promoter of human apoA-I gene. {yields} TNF{alpha} acts by weakening of promoter competition within apoA-I gene (promoter switching). {yields} MEK1/2 and nuclear receptors PPAR{alpha} and LXRs take part in apoA-I promoter switching. -- Abstract: Human apolipoprotein A-I (ApoA-I) is a major structural and functional protein component of high-density lipoproteins. The expression of the apolipoprotein A-I gene (apoA-I) in hepatocytes is repressed by pro-inflammatory cytokines such as IL-1{beta} and TNF{alpha}. Recently, two novel additional (alternative) promoters for human apoA-I gene have been identified. Nothing is known about the role of alternative promoters in TNF{alpha}-mediated downregulation of apoA-I gene. In this article we report for the first time about the different effects of TNF{alpha} on two alternative promoters of human apoA-I gene. Stimulation of HepG2 cells by TNF{alpha} leads to activation of the distal alternative apoA-I promoter and downregulation of the proximal alternative and the canonical apoA-I promoters. This effect is mediated by weakening of the promoter competition within human apoA-I 5'-regulatory region (apoA-I promoter switching) in the cells treated by TNF{alpha}. The MEK1/2-ERK1/2 cascade and nuclear receptors PPAR{alpha} and LXRs are important for TNF{alpha}-mediated apoA-I promoter switching.

  18. Data from a cross-sectional study on Apolipoprotein E (APOE-ε4 and snoring/sleep apnea in non-demented older adults

    Directory of Open Access Journals (Sweden)

    Angeliki Tsapanou

    2015-12-01

    Full Text Available In the present data, we provide the details of the cross-sectional study, from the Washington Heights-Inwood Community Aging Project (WHICAP that examined the association between Apolipoprotein E (APOE-ε4 and snoring/sleep apnea. A total of 1944 non-demented older adults constituted our sample. Sleep dysfunction was measured using sleep categories derived from the Medical Outcomes Study Sleep Scale. Stratified analyses were conducted in order to examine the association between APOE-ε4 and sleep variables by ethnic group. For further analyses and enhanced discussion, see “Examining the association between Apolipoprotein E (APOE and self-reported sleep disturbances in non-demented older adults” by Tsapanou et al. (2015 [1].

  19. Involvement of toll-like receptor 2 and 4 in association between dyslipidemia and osteoclast differentiation in apolipoprotein E deficient rat periodontium

    OpenAIRE

    Tomofuji, Takaaki; Ekuni, Daisuke; Azuma, Tetsuji; Irie, Koichiro; Endo, Yasumasa; Kasuyama, Kenta; Yoneda, Toshiki; Morita, Manabu

    2013-01-01

    Background Dyslipidemia increases circulating levels of oxidized low-density lipoprotein (OxLDL) and this may induce alveolar bone loss through toll-like receptor (TLR) 2 and 4. The purpose of this study was to investigate the effects of dyslipidemia on osteoclast differentiation associated with TLR2 and TLR4 in periodontal tissues using a rat dyslipidemia (apolipoprotein E deficient) model. Methods Levels of plasma OxLDL, and the cholesterol and phospholipid profiles in plasma lipoproteins w...

  20. Probucol prevents early coronary heart disease and death in the high-density lipoprotein receptor SR-BI/apolipoprotein E double knockout mouse

    OpenAIRE

    Braun, Anne; Zhang, Songwen; Miettinen, Helena E.; Ebrahim, Shamsah; Holm, Teresa M.; Vasile, Eliza; Mark J Post; Yoerger, Danita M.; Picard, Michael H.; Joshua L. Krieger; Andrews, Nancy C.; Simons, Michael; Krieger, Monty

    2003-01-01

    Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean a...

  1. Apolipoprotein(a) Inhibits In Vitro Tube Formation in Endothelial Cells: Identification of Roles for Kringle V and the Plasminogen Activation System

    OpenAIRE

    Lei Liu; Boffa, Michael B.; Koschinsky, Marlys L.

    2013-01-01

    Elevated plasma concentrations of lipoprotein(a) are associated with increased risk for atherothrombotic diseases. Apolipoprotein(a), the unique glycoprotein component of lipoprotein(a), is characterized by the presence of multiple kringle domains, and shares a high degree of sequence homology with the serine protease zymogen plasminogen. It has been shown that angiostatin, a proteolytic fragment of plasminogen containing kringles 1-4, can effectively inhibit angiogenesis. Moreover, proteolyt...

  2. Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans

    OpenAIRE

    Sakamoto, Norihisa; Tsuji, Kazuhide; Muul, Linda M.; Lawler, Ann M.; Petricoin, Emanuel F.; Candotti, Fabio; Metcalf, Julia A.; Tavel, Jorge A; Lane, H. Clifford; Urba, Walter J; Fox, Bernard A.; Varki, Ajit; Lunney, Joan K; Rosenberg, Amy S.

    2007-01-01

    Recent studies have demonstrated that cell populations intended for therapeutic purposes that are cultured in heterologous animal products can acquire xenoantigens, potentially limiting their utility. In investigations of the immune response to murine embryonic stem cells, we found that a strong antibody response was generated after the second infusion. Both polyclonal and monoclonal antibody responses, derived from immunized mice, were found to be specific for bovine apolipoprotein B-100, wh...

  3. Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial

    OpenAIRE

    Langefeld, Carl D.; Divers, Jasmin; Nicholas M. Pajewski; Hawfield, Amret T.; Reboussin, David M.; Bild, Diane E.; Kaysen, George A.; Kimmel, Paul L; Raj, Dominic; Ricardo, Ana C.; Wright, Jackson T; Sedor, John R.; Rocco, Michael V.; Freedman, Barry I.

    2014-01-01

    Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans. Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2,571 African Americans from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logist...

  4. Das humane Apolipoprotein D als Gerüststruktur für neuartige Bindungsproteine mit Affinität zu Protein-Antigenen

    OpenAIRE

    Vogt, Martin

    2005-01-01

    Die Bindungseigenschaften des humanen Apolipoprotein D (ApoD), eines Vertreters der Lipocalin-Proteinfamilie, wurden so verändert, daß anstelle der natürlichen niedermolekularen Liganden ein vorgegebenes Protein-Antigen erkannt wird. Dazu wurde die gentechnische Produktion des ApoD in E. coli etabliert und dessen Bindungseigenschaften charakterisiert, wobei Progesteron und Arachidonsäure als physiologische Liganden bestätigt wurden, nicht jedoch andere Verbindungen, die zuvor als Liganden dis...

  5. Western-type diet modulates inflammatory responses and impairs functional outcome following permanent middle cerebral artery occlusion in aged mice expressing the human apolipoprotein E4 allele

    OpenAIRE

    Dhungana, Hiramani; Rolova, Taisia; Savchenko, Ekaterina; Wojciechowski, Sara; Savolainen, Kaisa; Ruotsalainen, Anna-Kaisa; Sullivan, Patrick M.; Koistinaho, Jari; Malm, Tarja

    2013-01-01

    Background Numerous clinical trials in stroke have failed, most probably partially due to preclinical studies using young, healthy male rodents with little relevance to the heterogenic conditions of human stroke. Co-morbid conditions such as atherosclerosis and infections coupled with advanced age are known to contribute to increased risk of cerebrovascular diseases. Clinical and preclinical studies have shown that the E4 allele of human apolipoprotein (ApoE4) is linked to poorer outcome in v...

  6. On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy

    DEFF Research Database (Denmark)

    Mora, Samia; Glynn, Robert J; Boekholdt, S Matthijs;

    2012-01-01

    The goal of this study was to determine whether residual risk after high-dose statin therapy for primary prevention individuals with reduced levels of low-density lipoprotein cholesterol (LDL-C) is related to on-treatment apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), tri......-HDL-C), trigylcerides, or lipid ratios, and how they compare with on-treatment LDL-C....

  7. ATR–FTIR, a new tool to analyze the oligomeric content of Aβ samples in the presence of apolipoprotein E isoforms

    OpenAIRE

    Cerf, Emilie; Ruysschaert, Jean-Marie; Goormaghtigh, Erik; Raussens, Vincent

    2010-01-01

    Alzheimer̕s disease (AD) is a neurodegenerative disorder caused by the aggregation of the amyloid-beta peptide (Aβ), leading to amyloid plaques deposition in the brain. Although Aβ aggregation pathway still remains unclear, recent studies point out the enhanced toxicity of oligomers compared to fibrils. The E4 isoform of apolipoprotein E (ApoE) is the major risk factor in AD as people carrying one ɛ4 allele have significantly higher chances to develop the disease. Nevertheless, this phenomeno...

  8. The influence of statin-fibrate combination therapy on lipids profile and apolipoprotein A5 in patients with acute coronary syndrome

    OpenAIRE

    Li, Xiang-ping; Gong, Hai-rong; Huang, Xian-sheng; Huang, Wen-Yu; Zhao, Shui-ping

    2013-01-01

    Background Statin-fibrate combination therapy has been used to treat patients with acute coronary syndrome (ACS) complicated by elevated triglycerides (TG) and decreased high density lipoprotein cholesterol (HDL-C). The purpose of this study was to evaluate the influence of the combination therapy on lipids profile and apolipoprotein A5 (apoA5) level in patients with ACS. Methods One hundred and four patients with ACS were recruited and randomly assigned into two groups: one was statin group ...

  9. Identification of the ancestral haplotype for apolipoprotein B suggests an African origin of Homo sapiens sapiens and traces their subsequent migration to Europe and the Pacific.

    OpenAIRE

    Rapacz, J; Chen, L.; Butler-Brunner, E; Wu, M J; Hasler-Rapacz, J O; Butler, R.; Schumaker, V N

    1991-01-01

    The probable ancestral haplotype for human apolipoprotein B (apoB) has been identified through immunological analysis of chimpanzee and gorilla serum and sequence analysis of their DNA. Moreover, the frequency of this ancestral apoB haplotype among different human populations provides strong support for the African origin of Homo sapiens sapiens and their subsequent migration from Africa to Europe and to the Pacific. The approach used here for the identification of the ancestral human apoB ha...

  10. Structural organization of lipid phase and protein-lipid interface in apolipoprotein-phospholipid recombinants: influence of cholesterol.

    Science.gov (United States)

    Dergunov, A D; Taveirne, J; Vanloo, B; Caster, H; Rosseneu, M

    1997-06-01

    The complexes of individual human plasma apolipoproteins (apo) A-I, E and A-II with dipalmitoylphosphatidylcholine (DPPC) in the absence or in the presence of cholesterol (Chol) were prepared with initial DPPC/Chol/protein weight ratio as 3:0.15:1. ApoA-I/DPPC/Chol complexes with different protein content (initial DPPC/apoA-I weight ratios were changed from 10.5:1 to 2.6:1) but with a fixed initial DPPC/Chol weight ratio of 20:1 were also prepared. The complexes were isolated by gel-filtration and characterized by size and composition. ApoA-I- and apoA-II-complexes had the same size (80-84 A) and the complexes became more heterogeneous upon Chol inclusion; apoE-complexes were larger (97-100 A) and more homogeneous and Chol addition had no effect on their hydrodynamic properties. Chol seems to be excluded partially in the following manner for isolated complexes with different apo's: A-II > E > A-I. The possible existence of two lipid regions in the complexes differing in lipid dynamics - the lipid shell in the vicinity of apolipoprotein (boundary lipid) opposite to the remaining part of the lipid bilayer - has been studied by absorbance and fluorescence spectroscopy with cis-parinaric acid (cis-PA) and trans-parinaric acid (trans-PA) embedded into the complexes. Their application is based on a strong preference of trans-PA for solid lipid while cis-PA distributes more equally between co-existing fluid and solid lipid regions (Sklar et al. (1979) Biochemistry 18, 1707-1716). (1) For apoA-I-complexes, the partition of cis-PA between water and lipid phase at temperatures below and above the transition temperature of DPPC (T(t)) was insensitive to Chol and temperature, while partition of trans-PA into the lipid phase of Chol-containing complex was increased at high temperature and decreased at low temperature. These results seem to be related to trans-PA redistribution between Chol-rich and protein-rich lipid domains, the latter being more disordered at T T(t) compared

  11. Allelic variants of the genes of apolipoproteins B and CII in patients with coronary heart disease and in healthy individuals from the Moscow population

    Energy Technology Data Exchange (ETDEWEB)

    Pogoda, T.V.; Kolosova, T.V.; Lyudvikova, E.K. [Institute of Molecular Genetics, Moscow (Russian Federation)] [and others

    1995-07-01

    Allelic frequencies of a microsatellite of the apolipoprotein CII gene (APOCII) and a minisatellite of the apolipoprotein B gene (APOB) were studied by using polymerase chain reaction (PCR). The study was conducted on a random sample of male Moscow inhabitants and a sample of patients with coronary heart disease (CHD) from the same population. Fourteen variants of the APOB minisatellite (the 82% heterozygosity level) and 13 alleles of the APOCII microsatellite (the 85% heterozygosity level) were found. CHD patients significantly differed from the control group in the distributions of alleles in these loci: APOB 32, APOB 46, APOB 48, and APOB 50 as well as APOCII 17 and APOCII 29 were found more frequently. A relationship was found between the distributions of APOB and APOCII in the CHD patients. The CHD patients with alleles APOCII 21 and APOCII 30 very often had the allele APOB 32; and patients with the genotype APOB 34, 36 had the allele APOCII 29 even more often than affected individuals in general. Individuals of the control group with the allele APOCII30 exhibited hypertriglyceridemia without increased levels of total cholesterol and apolipoprotein B in plasma. 14 refs., 3 figs., 6 tabs.

  12. Localized Surface Plasmons in Vibrating Graphene Nanodisks

    DEFF Research Database (Denmark)

    Wang, Weihua; Li, Bo-Hong; Stassen, Erik;

    2016-01-01

    in graphene disks have the additional benefit to be highly tunable via electrical stimulation. Mechanical vibrations create structural deformations in ways where the excitation of localized surface plasmons can be strongly modulated. We show that the spectral shift in such a scenario is determined...... by a complex interplay between the symmetry and shape of the modal vibrations and the plasmonic mode pattern. Tuning confined modes of light in graphene via acoustic excitations, paves new avenues in shaping the sensitivity of plasmonic detectors, and in the enhancement of the interaction with optical emitters...

  13. Localized Surface Plasmons in Vibrating Graphene Nanodisks

    CERN Document Server

    Wang, Weihua; Mortensen, N Asger; Christensen, Johan

    2015-01-01

    Localized surface plasmons are confined collective oscillations of electrons in metallic nanoparticles. When driven by light, the optical response is dictated by geometrical parameters and the dielectric environment and plasmons are therefore extremely important for sensing applications. Plasmons in graphene disks have the additional benefit to be highly tunable via electrical stimulation. Mechanical vibrations create structural deformations in ways where the excitation of localized surface plasmons can be strongly modulated. We show that the spectral shift in such a scenario is determined by a complex interplay between the symmetry and shape of the modal vibrations and the plasmonic mode pattern. Tuning confined modes of light in graphene via acoustic excitations, paves new avenues in shaping the sensitivity of plasmonic detectors, and in the enhancement of the interaction with optical emitters, such as molecules, for future nanophotonic devices.

  14. Incore stabilizer

    International Nuclear Information System (INIS)

    The present invention provides an incore stabilizer for preventing collision of neutron guide tubes with each other or with other equipments in a BWR-type reactor even if oscillations in one identical phase such as earthquakes are exerted. Namely, a first connection member connected to a reactor core shroud is inserted between a tuning fork-like branched second connecting members connected to a neutron instrumentation guide tube. A pin is pierced to the second connecting member from above through a pin hole, to connect both of the connection members by a nut disposed below. In this case, double eccentric sleeves are fitted to the first connection member and it is inserted to the second connection members, and they are connected by using pins and nuts. With such a constitution, even if the pin hole of the second connection member is eccentrically deviated, the eccentricity can easily be absorbed by rotating the double eccentric sleeves. As a result, pins can be attached easily. In addition, abrasion resistance of the inner surface of the pin hole is enhanced by using a material of high abrasion resistance for the eccentric sleeves. (I.S.)

  15. Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuehai [Cardiovascular Department, Liaocheng People’s Hospital of Shandong University, Liaocheng, Shandong 252000 (China); Cardiovascular Department, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000 (China); Lu, Huixia [The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Huang, Ziyang, E-mail: huangziyang666@126.com [Cardiovascular Department, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000 (China); Lin, Huili [Cardiovascular Department, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000 (China); Lei, Zhenmin [Department of OB/GYN, University of Louisville School of Medicine, Louisville, KY 40292 (United States); Chen, Xiaoqing [Department of Rheumatism and Immunology, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000 (China); Tang, Mengxiong; Gao, Fei; Dong, Mei [The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Li, Rongda [Department of Rheumatism and Immunology, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000 (China); Lin, Ling, E-mail: qzlinl@163.com [Department of Rheumatism and Immunology, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000 (China)

    2014-07-18

    Highlights: • Titers of ANA and anti-dsDNA antibodies were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • The spleen weights and glomerular areas were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • Expressions of IgG and C3 in glomeruli were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • IgG, C3 and macrophage infiltration in aortic plaques were found in ApoE{sup −/−} mice. - Abstract: Background: Apolipoprotein E-knockout (ApoE{sup −/−}) mice is a classic model of atherosclerosis. We have found that ApoE{sup −/−} mice showed splenomegaly, higher titers of serum anti-nuclear antibody (ANA) and anti-dsDNA antibody compared with C57B6/L (B6) mice. However, whether ApoE{sup −/−} mice show autoimmune injury remains unclear. Methods and results: Six females and six males in each group, ApoE{sup −/−}, Fas{sup −/−} and B6 mice, were used in this study. The titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein were measured by ELISA after 4 months of high-fat diet. The spleen weight and the glomerular area were determined. The expressions of IgG, C3 and macrophage in kidney and atherosclerotic plaque were detected by immunostaining followed by morphometric analysis. Similar to the characteristics of Fas{sup −/−} mice, a model of systemic lupus erythematosus (SLE), ApoE{sup −/−} mice, especially female, displayed significant increases of spleen weight and glomerular area when compared to B6 mice. Also, elevated titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein. Moreover, the expressions of IgG, C3 and macrophage in glomeruli and aortic plaques were found in ApoE{sup −/−} mice. In addition, the IgG and C3 expressions in glomeruli and plaques significantly increased (or a trend of increase) in female ApoE{sup −/−} mice compared with males. Conclusions: Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta.

  16. Receptor-selective IL-4 mutein modulates inflammatory vascular cell phenotypes and attenuates atherogenesis in apolipoprotein E-knockout mice.

    Science.gov (United States)

    Lin, Yanhui; Chen, Zhiheng; Kato, Seiya

    2015-08-01

    The therapeutic potential of interleukin-4-mediated immunomodulation has not been proven in atherogenesis. Type I IL-4 receptor consists of IL-4Rα and a common γ chain, whereas type II IL-4R is a heterodimer of IL-4Rα and IL-13Rα1. Reportedly, the human IL-4 mutein IL-4/R121E is able to act as an IL-4RI-specific agonist. Here, we investigated the effect of receptor-specific IL-4 mutein on vascular cell phenotypes and atherogenesis. Initially, a plasmid expressing murine IL-4/Q116E, analogous to human IL-4/R121E, was transfected to vascular lineage cells in-vitro. IL-4/Q116E induced the activation of STAT6 in b.End3 endothelial cells, Mm1 macrophages, and splenocytes isolated from C57BL6/J (B6) mice, but it failed to activate STAT6 in SMC and J774.1 macrophages. IL-4/Q116E induced the expression of vascular cell adhesion protein-1 in b.End3 cells but not in SMC. IL-4/Q116E did not exhibit pro-inflammatory actions in either macrophage cell line. Splenocytes were also infected with an adenovirus vector expressing IL-4/Q116E (AdIL-4/Q116E). Enzyme-linked immunosorbent assay for interferon-γ, IL-10 and IL-13 revealed that AdIL-4/Q116E-infected splenocytes showed Th2 deviation. Th2 deviation and M2 marker up-regulation were further revealed in ex-vivo assays using the splenocytes isolated from AdIL-4/Q116E-infected apolipoprotein-E knockout (ApoEKO) mice. Finally, adenoviral induction of IL-4/Q116E, but not wild type IL-4, double mutein IL-4/Q116D/Y119D or control β-galactosidase, significantly attenuated in-vivo atherogenesis of ApoEKO mice. Our data suggest that IL-4 signaling plays a pivotal role in the regulation of vascular cell phenotypes, and atherogenesis. The IL-4RI-selective mutein IL-4/Q116E may have therapeutic potential in vascular diseases. PMID:26093164

  17. Apolipoprotein E inhibits osteoclast differentiation via regulation of c-Fos, NFATc1 and NF-κB

    International Nuclear Information System (INIS)

    Apolipoprotein E (ApoE) plays a major role in the transport and metabolism of lipid. Other functions of ApoE include modulation of innate and adaptive immune responses. The expression of ApoE in osteoblasts and its relevance with bone formation have also been reported. However, the effect of ApoE on osteoclasts has not yet been examined. Here, we investigated the role of ApoE in osteoclast differentiation using bone marrow-derived macrophages (BMMs) and RAW264.7 cells. We found a down-regulation of ApoE gene expression during osteoclastic differentiation of those cells. Overexpression of ApoE in BMMs and RAW264.7 cells significantly blocked the induction of c-Fos and nuclear factor of activated T cell c1 (NFATc1), transcription factors critical for expression of osteoclast marker genes, by receptor activator of nuclear factor κB ligand (RANKL), the osteoclast differentiation factor. ApoE inhibited osteoclast differentiation, as measured by decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (MNCs). In addition, ApoE reduced the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and ATPase, H+ transporting, lysosomal 38 kDa, V0 subunit d2 (ATP6v0d2), genes involved in cell–cell fusion during osteoclastogenesis. Knock-down of ApoE using a specific siRNA promoted the RANKL-mediated induction of osteoclast differentiation. While ApoE did not affect the activation of ERK, JNK, and p38 MAPK signaling pathways by RANKL, the phosphorylation of p65 trans-activation domain on serine 536 and transcription activity of NF-κB were reduced by ApoE overexpression. These findings suggest that ApoE plays an inhibitory role in osteoclast differentiation via the suppression of RANKL-dependent activation of NF-κB and induction of c-Fos and NFATc1. - Highlights: ► Apolipoprotein E (ApoE) significantly inhibited osteoclast differentiation and activation of NF-κB. ► ApoE decreased the induction of osteoclast marker genes

  18. Apolipoprotein E inhibits osteoclast differentiation via regulation of c-Fos, NFATc1 and NF-κB

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Woo-Shin; Kim, Hyung Joon; Lee, Zang Hee [Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, 28 Yeongon-Dong, Chongno-Gu, Seoul 110-749 (Korea, Republic of); Lee, Youngkyun [Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Kim, Hong-Hee, E-mail: hhbkim@snu.ac.kr [Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, 28 Yeongon-Dong, Chongno-Gu, Seoul 110-749 (Korea, Republic of)

    2013-02-15

    Apolipoprotein E (ApoE) plays a major role in the transport and metabolism of lipid. Other functions of ApoE include modulation of innate and adaptive immune responses. The expression of ApoE in osteoblasts and its relevance with bone formation have also been reported. However, the effect of ApoE on osteoclasts has not yet been examined. Here, we investigated the role of ApoE in osteoclast differentiation using bone marrow-derived macrophages (BMMs) and RAW264.7 cells. We found a down-regulation of ApoE gene expression during osteoclastic differentiation of those cells. Overexpression of ApoE in BMMs and RAW264.7 cells significantly blocked the induction of c-Fos and nuclear factor of activated T cell c1 (NFATc1), transcription factors critical for expression of osteoclast marker genes, by receptor activator of nuclear factor κB ligand (RANKL), the osteoclast differentiation factor. ApoE inhibited osteoclast differentiation, as measured by decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (MNCs). In addition, ApoE reduced the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and ATPase, H{sup +} transporting, lysosomal 38 kDa, V0 subunit d2 (ATP6v0d2), genes involved in cell–cell fusion during osteoclastogenesis. Knock-down of ApoE using a specific siRNA promoted the RANKL-mediated induction of osteoclast differentiation. While ApoE did not affect the activation of ERK, JNK, and p38 MAPK signaling pathways by RANKL, the phosphorylation of p65 trans-activation domain on serine 536 and transcription activity of NF-κB were reduced by ApoE overexpression. These findings suggest that ApoE plays an inhibitory role in osteoclast differentiation via the suppression of RANKL-dependent activation of NF-κB and induction of c-Fos and NFATc1. - Highlights: ► Apolipoprotein E (ApoE) significantly inhibited osteoclast differentiation and activation of NF-κB. ► ApoE decreased the induction of osteoclast marker

  19. Metabolic hormones, apolipoproteins, adipokines, and cytokines in the alveolar lining fluid of healthy adults: compartmentalization and physiological correlates.

    Directory of Open Access Journals (Sweden)

    Carlos O Mendivil

    Full Text Available Our current understanding of hormone regulation in lung parenchyma is quite limited. We aimed to quantify a diverse array of biologically relevant protein mediators in alveolar lining fluid (ALF, compared to serum concentrations, and explore factors associated with protein compartmentalization on either side of the air-blood barrier.Participants were 24 healthy adult non-smoker volunteers without respiratory symptoms or significant medical conditions, with normal lung exams and office spirometry. Cell-free bronchoalveolar lavage fluid and serum were analyzed for 24 proteins (including enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines using a highly sensitive multiplex ELISA. Measurements were normalized to ALF concentrations. The ALF:serum concentration ratios were examined in relation to measures of protein size, hydrophobicity, charge, and to participant clinical and spirometric values.ALF measurements from 24 individuals detected 19 proteins, including adiponectin, adipsin, apoA-I, apoA-II, apoB, apoC-II, apoC-III, apoE, C-reactive protein, ghrelin, glucose-dependent insulinotropic peptide (GIP, glucagon-like peptide-1 (GLP-1, glucagon, insulin, leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, resistin, and visfatin. C-peptide and serpin E1 were not detected in ALF for any individual, and IL-6, IL-10, and TNF-alpha were not detected in either ALF or serum for any individual. In general, ALF levels were similar or lower in concentration for most proteins compared to serum. However, ghrelin, resistin, insulin, visfatin and GLP-1 had ALF concentrations significantly higher compared to serum. Importantly, elevated ALF:serum ratios of ghrelin, visfatin and resistin correlated with protein net charge and isoelectric point, but not with molecular weight or hydrophobicity.Biologically relevant enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines can be detected in the ALF of

  20. Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta

    International Nuclear Information System (INIS)

    Highlights: • Titers of ANA and anti-dsDNA antibodies were similar in ApoE−/− and Fas−/− mice. • The spleen weights and glomerular areas were similar in ApoE−/− and Fas−/− mice. • Expressions of IgG and C3 in glomeruli were similar in ApoE−/− and Fas−/− mice. • IgG, C3 and macrophage infiltration in aortic plaques were found in ApoE−/− mice. - Abstract: Background: Apolipoprotein E-knockout (ApoE−/−) mice is a classic model of atherosclerosis. We have found that ApoE−/− mice showed splenomegaly, higher titers of serum anti-nuclear antibody (ANA) and anti-dsDNA antibody compared with C57B6/L (B6) mice. However, whether ApoE−/− mice show autoimmune injury remains unclear. Methods and results: Six females and six males in each group, ApoE−/−, Fas−/− and B6 mice, were used in this study. The titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein were measured by ELISA after 4 months of high-fat diet. The spleen weight and the glomerular area were determined. The expressions of IgG, C3 and macrophage in kidney and atherosclerotic plaque were detected by immunostaining followed by morphometric analysis. Similar to the characteristics of Fas−/− mice, a model of systemic lupus erythematosus (SLE), ApoE−/− mice, especially female, displayed significant increases of spleen weight and glomerular area when compared to B6 mice. Also, elevated titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein. Moreover, the expressions of IgG, C3 and macrophage in glomeruli and aortic plaques were found in ApoE−/− mice. In addition, the IgG and C3 expressions in glomeruli and plaques significantly increased (or a trend of increase) in female ApoE−/− mice compared with males. Conclusions: Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta

  1. Interactions of the apolipoprotein C-III 3238C>G polymorphism and alcohol consumption on serum triglyceride levels

    Directory of Open Access Journals (Sweden)

    Ruixing Yin

    2010-08-01

    Full Text Available Abstract Background Both apolipoprotein (Apo C-III gene polymorphism and alcohol consumption have been associated with increased serum triglyceride (TG levels, but their interactions on serum TG levels are not well known. The present study was undertaken to detect the interactions of the ApoC-III 3238C>G (rs5128 polymorphism and alcohol consumption on serum TG levels. Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoC-III 3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Interactions of the ApoC-III 3238C>G genotype and alcohol consumption was assessed by using a cross-product term between genotypes and the aforementioned factor. Results Serum total cholesterol (TC, TG, high-density lipoprotein cholesterol (HDL-C, ApoA-I and ApoB levels were higher in drinkers than in nondrinkers (P P P P P P P P Conclusions This study suggests that the ApoC-III 3238CG heterozygotes benefited more from alcohol consumption than CC and GG homozygotes in increasing serum levels of HDL-C, ApoA-I, and the ratio of ApoA-I to ApoB, and lowering serum levels of TC and TG.

  2. Primary Genetic Investigation of a Hyperlipidemia Model: Molecular Characteristics and Variants of the Apolipoprotein E Gene in Mongolian Gerbil

    Directory of Open Access Journals (Sweden)

    Yuehuan Liu

    2014-01-01

    Full Text Available The objective of this work was to establish a novel Mongolian gerbil (Meriones unguiculatus hyperlipidemia model and to investigate its susceptibility genetic basis. Two rodent (gerbil and rat hyperlipidemia models were induced by feeding a high fat/high-cholesterol (HF/HC diet. There were significant increases of serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C, and high-density lipoprotein cholesterol (HDL-C in gerbils within a 4-week modeling period. About 10–30% of >8-month-old individuals developed hyperlipidemia spontaneously. The apolipoprotein E (ApoE gene was cloned by merging a sequence of rapid amplification of cDNA ends (RACE and nested polymerase chain reaction products. The results revealed an open reading frame of 948 bp, encoding a protein of 298 amino acids. The gene without a 5′-UTR region in the first intron was highly homologous to human Apo-A-I and rat Apo-A-IV. The distribution of expression of the ApoE gene in liver, brain, heart, lung, kidney, and adrenal gland was detected by an ABC immunohistochemical procedure. Three single nucleotide polymorphisms (SNPs; C97T, G781T, and A1774T were first found using PCR-single-strand conformation polymorphism (PCR-SSCP in a closed population containing 444 animals. Correlation analysis confirmed that new SNPs , age, and gender were associated significantly (P<0.05 with hyperlipidemia.

  3. Apolipoprotein E polymorphism and acute ischemic stroke: a diffusion- and perfusion-weighted magnetic resonance imaging study.

    Science.gov (United States)

    Liu, Yawu; Laakso, Mikko P; Karonen, Jari O; Vanninen, Ritva L; Nuutinen, Juho; Soimakallio, Seppo; Aronen, Hannu J

    2002-11-01

    Diffusion- and perfusion-weighted magnetic resonance imaging (MRI) was used to study the putative effects of apolipoprotein E (ApoE) polymorphism in stroke. Thirty-one patients with acute stroke, comparative for age and gender were scanned, nine of whom were ApoE allele epsilon 4 carriers. Initially, less than 24 hours from the onset of stroke, the epsilon 4 carriers had significantly smaller volumes of hypoperfusion on relative cerebral blood volume map (P = 0.001), and smaller infarct volumes (P = 0.008) compared with the noncarriers. By day 8, this difference in the infarct volumes had disappeared, suggesting relatively enhanced infarct growth. On average, the total infarct volume increased 145% of the initial infarct volume in the epsilon 4 carriers, and 84% in the noncarriers. There were strong correlations between the imaging findings and clinical status initially and with the outcome 3 months after the stroke in the epsilon 4 noncarriers, but, with a single exception at acute phase, a lack thereof in the epsilon 4 carriers. These patterns were virtually similar in a subgroup of patients with middle cerebral artery stroke. These data support the hypothesis of increased general vulnerability of the brain in the epsilon 4 carriers. Thus, the effects of ApoE polymorphism should be accounted for when interpreting diffusion- and perfusion-weighted MRI studies, particularly if predicting lesion growth. PMID:12439291

  4. Impact of Apolipoprotein B on Hepatosteatosis in a Population Infected with Hepatitis C Virus: A Cross-Sectional Observational Study

    Directory of Open Access Journals (Sweden)

    Ming-Shyan Lin

    2016-04-01

    Full Text Available Objective: Non-alcoholic fatty liver disease (NAFLD is an established risk factor for diabetes, cardiovascular disease, antiviral treatment resistance, and progression of chronic hepatitis C virus (HCV infection to fibrosis. Apolipoprotein-B 100 (ApoB-100 is a dyslipidemia marker and steatosis predictor. We assess the correlation between ApoB-100 and hepatosteatosis. Methods: This cross-sectional study enrolled 1,218 HCV-seropositive participants from a 2012-2013 health checkup in Taiwan. NAFLD was detected using ultrasound. All anthropometric and laboratory studies that included ApoB-100 were evaluated whether or not ApoB-100 predicts NAFLD. Logistic regression was also used to examine the association between ApoB-100 and NAFLD. Results: Participants were 47.16 ± 16.08 years old (mean age. The overall prevalence of NAFLD was 35.8% (n = 436; 32.8% men, 38.1% women. Participants with ApoB-100 ≥ 8 had a significantly higher incidence of NAFLD (39.4 vs. 29.4%; 95% CI 0.044-0.156; p Conclusion: ApoB-100 is strongly associated with NAFLD in people with non-genotype 3 HCV; greater ApoB-100 content is significantly correlated with higher-grade hepatosteatosis.

  5. TO901317 regulating apolipoprotein M expression mediates via the farnesoid X receptor pathway in Caco-2 cells

    Directory of Open Access Journals (Sweden)

    Berggren-Söderlund Maria

    2011-11-01

    Full Text Available Abstract Background Apolipoprotein M (apoM may have potential antiatherosclerotic properties. It has been reported that apoM expression could be regulated by many intracellar and extracellar factors. In the present study we further investigated regulation of apoM expression in Caco-2 cells stimulated by a liver X receptor (LXR agonist, TO901317. Materials and methods Caco-2 cells were cultured in the presence of either TO901317, farnesoid X receptor (FXR antagonist guggulsterone or TO901317 together with guggulsterone at different concentrations for 24 hrs. The mRNA levels of ATP-binding cassette transporter A1 (ABCA1, apoA1, apoM, liver receptor homologue-1 (LRH-1 and short heterodimer partner 1 (SHP1 were determined by real-time RT-PCR. Results When Caco-2 cell cultured with TO901317 alone, the mRNA levels of ABCA1, apoA1, apoM, LRH-1 and SHP1 were significantly increased with dose-dependent manners (p p Conclusion The present study demonstrated that LXR agonist TO901317 induced apoM expression in Caco-2 cells might be mediated via the LXR/FXR pathway.

  6. Computational Design of Apolipoprotein E4 Inhibitors for Alzheimer’s Disease Therapy from Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Hung-Jin Huang

    2014-01-01

    Full Text Available Apolipoprotein E4 (Apo E4 is the major genetic risk factor in the causation of Alzheimer’s disease (AD. In this study we utilize virtual screening of the world’s largest traditional Chinese medicine (TCM database and investigate potential compounds for the inhibition of ApoE4. We present the top three TCM candidates: Solapalmitine, Isodesacetyluvaricin, and Budmunchiamine L5 for further investigation. Dynamics analysis and molecular dynamics (MD simulation were used to simulate protein-ligand complexes for observing the interactions and protein variations. Budmunchiamine L5 did not have the highest score from virtual screening; however, the dynamics pose is similar to the initial docking pose after MD simulation. Trajectory analysis reveals that Budmunchiamine L5 was stable over all simulation times. The migration distance of Budmunchiamine L5 illustrates that docked ligands are not variable from the initial docked site. Interestingly, Arg158 was observed to form H-bonds with Budmunchiamine L5 in the docking pose and MD snapshot, which indicates that the TCM compounds could stably bind to ApoE4. Our results show that Budmunchiamine L5 has good absorption, blood brain barrier (BBB penetration, and less toxicity according to absorption, distribution, metabolism, excretion, and toxicity (ADMET prediction and could, therefore, be safely used for developing novel ApoE4 inhibitors.

  7. Quantum-dot biosensor for hybridization and detection of R3500Q mutation of apolipoprotein B-100 gene.

    Science.gov (United States)

    Mazloum-Ardakani, Mohammad; Aghaei, Roghayyeh; Heidari, Mohammad Mehdi

    2015-10-15

    A quantum-dot electrode system was developed as a transducer surface for covalent immobilization of a designed synthetic ApoB-100 specific probe, DNA hybridization and monitoring of DNA synthesis for the sensitive detection of R3500Q mutation of apolipoprotein B-100 (ApoB-100) gene. CdS-QDs cause an improvement in the fundamental characteristics of the electrode interface, such as its electroactive surface area, diffusion coefficient and electron transfer kinetics. The sensing characteristics of this biosensor offer a suitable potential for detection of target oligonucleotide with a detection limit of 3.4 × 10(-17)M. Also, the electrochemical responses of single-stranded DNA (ssDNA), DNA hybridization and DNA synthesis were investigated using electrochemical impedance spectroscopy (EIS). The extracted genomic DNA was detected based on changes in the charge transfer resistance (RCT) with [Fe(CN)6](3-/4-) as a redox probe. The proposed biosensor can distinguish between the normal sequence and the mutant sequence of ApoB-100 gene, promising a possibility to apply the QD-based biosensor for clinical investigations. PMID:26022781

  8. Apolipoprotein E gene polymorphism and its effect on anthropometric measures in normoglycemic subjects and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Tabatabaei-Malazy Ozra

    2012-10-01

    Full Text Available Abstract Background Apolipoprotein E (apo E plays a major role in lipid metabolism, obesity and accordingly in development of diabetes and coronary heart disease (CHD. Our main objective was to evaluate the association between apo E gene polymorphism with anthropometric measures. Methods Participants were selected from zone 17 Tehran/Iran. We assessed height, weight, body mass index (BMI, waist circumference (WC, blood pressure, serum fasting blood sugar, total cholesterol and triglycerides. Genotyping for apo E gene polymorphism was carried out using PCR-RFLP technique. Results Among total study population (n=311, 156 subjects were diabetic. The apo E3/E3 was the most common genotype in our population while E2 and E4 alleles had lower frequencies, respectively. After adjustment for diabetes, the apo E2 and E4 alleles were significantly associated with hypercholesterolemia and WC, respectively (p= 0.009, 0.034. This association was also related to sex and age. The probability of having abdominal obesity in E4 allele carriers was increased from 0.22 to 8.12 in women and to 3.08 in age ≥ 50 years. Conclusions Apo E polymorphism had significant influences on WC and total cholesterol level in patients with type 2 diabetes. This study highlights the importance of lifestyle modifications which may be more beneficial in hypercholesterolemic women carriers of E2 and E4 alleles concomitant central obesity.

  9. Selective proteolysis of apolipoprotein B-100 by Arg-gingipain mediates atherosclerosis progression accelerated by bacterial exposure.

    Science.gov (United States)

    Hashimoto, Munetaka; Kadowaki, Tomoko; Tsukuba, Takayuki; Yamamoto, Kenji

    2006-11-01

    Epidemiological studies suggest the association of periodontal infections with atherosclerosis, however, the mechanism underlying this association remains poorly understood. Porphyromonas gingivalis is the primary etiologic agent of adult periodontitis and produces a unique class of cysteine proteinases consisting of Arg-gingipain (Rgp) and Lys-gingipain (Kgp). To elucidate key mechanisms for progression of atherosclerosis by P. gingivalis infection, we tested the effects of the disruption of genes encoding Rgp and/or Kgp and inhibitors specific for the respective enzymes on atherosclerosis progression in apolipoprotein E-knockout mice. Repeated intravenous injection of wild-type P. gingivalis resulted in an increase in atherosclerotic lesions as well as an increase in the serum LDL cholesterol and a decrease of HDL cholesterol in these animals. LDL particles in P. gingivalis-injected animals were modified as a result of selective proteolysis of apoB-100 in LDL particles. This modification of LDL by P. gingivalis resulted in an increase in LDL uptake by macrophages and consequent foam cell formation in vitro. The atherosclerotic changes induced by P. gingivalis infection were attenuated by disruption of Rgp-encoding genes or by an Rgp-specific inhibitor. Our results indicate that degradation of apoB-100 by Rgp plays a crucial role in the promotion of atherosclerosis by P. gingivalis infection. PMID:17030507

  10. Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment

    Directory of Open Access Journals (Sweden)

    Kahan Thomas

    2004-09-01

    Full Text Available Abstract Background Dyslipidemia has been associated with hypertension. The present study explored if polymorphisms in genes encoding proteins in lipid metabolism could be used as predictors for the individual response to antihypertensive treatment. Methods Ten single nucleotide polymorphisms (SNP in genes related to lipid metabolism were analysed by a microarray based minisequencing system in DNA samples from ninety-seven hypertensive subjects randomised to treatment with either 150 mg of the angiotensin II type 1 receptor blocker irbesartan or 50 mg of the β1-adrenergic receptor blocker atenolol for twelve weeks. Results The reduction in blood pressure was similar in both treatment groups. The SNP C711T in the apolipoprotein B gene was associated with the blood pressure response to irbesartan with an average reduction of 19 mmHg in the individuals carrying the C-allele, but not to atenolol. The C16730T polymorphism in the low density lipoprotein receptor gene predicted the change in systolic blood pressure in the atenolol group with an average reduction of 14 mmHg in the individuals carrying the C-allele. Conclusions Polymorphisms in genes encoding proteins in the lipid metabolism are associated with the response to antihypertensive treatment in a drug specific pattern. These results highlight the potential use of pharmacogenetics as a guide for individualised antihypertensive treatment, and also the role of lipids in blood pressure control.

  11. Mass spectrometry of transferrin and apolipoprotein C-III for diagnosis and screening of congenital disorder of glycosylation.

    Science.gov (United States)

    Wada, Yoshinao

    2016-06-01

    Congenital disorder of glycosylation (CDG), formerly representing a group of diseases due to defects in the biosynthetic pathway of protein N-glycosylation, currently covers a wide range of disorders affecting glycoconjugates. Since its first application to serum transferrin from a CDG patient with phosphomannomutase-2 deficiency in 1992, mass spectrometry (MS) has been playing a key role in identification and characterization of glycosylation defects affecting glycoproteins. MS of native transferrin detects a lack of glycans characteristic to the classical CDG-I type of molecular abnormality. Electrospray ionization MS of native transferrin, especially, allows glycoforms to be analyzed precisely but requires basic knowledge regarding deconvolution of multiply-charged ions which may generate ghost signals upon transformation into a singly-charged form. MS of glycopeptides from tryptic digestion of transferrin delineates site-specific glycoforms and reveals a delicate balance of donor/acceptor substrates or the conformational effect of nascent proteins in cells. Matrix-assisted laser desorption ionization MS of apolipoprotein C-III is a simple method of elucidating the profiles of mucin-type core 1 O-glycans including site occupancy and glycoforms. In this technological review, the principle and pitfalls of MS for CDG are discussed and mass spectra of various types of CDG are presented. PMID:26873821

  12. A case report of hereditary apolipoprotein A-I amyloidosis associated with a novel APOA1 mutation and variable phenotype.

    Science.gov (United States)

    Tougaard, Birgitte G; Pedersen, Katja Venborg; Krag, Søren Rasmus; Gilbertson, Janet A; Rowczenio, Dorota; Gillmore, Julian D; Birn, Henrik

    2016-09-01

    Apolipoprotein A-I (apo A-I) amyloidosis is a non-AL, non-AA, and non-transthyretin type of amyloidosis associated with mutations in the APOA1 gene inherited in an autosomal dominant fashion. It is a form of systemic amyloidosis, but at presentation, can also mimic localized amyloidosis. The renal presentation generally involves interstitial and medullary deposition of apo A-I amyloid protein. We describe the identification of apo A-I amyloidosis by mass spectrometry in a 52-year old male, with no family history of amyloidosis, presenting with nephrotic syndrome and associated with heterozygosity for a novel APOA1 mutation (c.220 T > A) which encodes the known amyloidogenic Trp50Arg variant. Renal amyloid deposits in this case were confined to the glomeruli alone, and the patient developed progressive renal impairment. One year after diagnosis, the patient had a successful kidney transplant from an unrelated donor. Pathogenic mutations in the APOA1 gene are generally associated with symptoms of amyloidosis. In this family however, genotyping of family members identified several unaffected carriers suggesting a variable disease penetrance, which has not been described before in this form of amyloidosis and has implications when counselling those with APOA1 mutations. PMID:27240838

  13. A novel peptide derived from human apolipoprotein E is an inhibitor of tumor growth and ocular angiogenesis.

    Directory of Open Access Journals (Sweden)

    Partha S Bhattacharjee

    Full Text Available Angiogenesis is a hallmark of tumor development and metastasis and now a validated target for cancer treatment. We previously reported that a novel dimer peptide (apoEdp derived from the receptor binding region of human apolipoprotein E (apoE inhibits virus-induced angiogenesis. However, its role in tumor anti-angiogenesis is unknown. This study demonstrates that apoEdp has anti-angiogenic property in vivo through reduction of tumor growth in a mouse model and ocular angiogenesis in a rabbit eye model. Our in vitro studies show that apoEdp inhibits human umbilical vein endothelial cell proliferation, migration, invasion and capillary tube formation. We document that apoEdp inhibits vascular endothelial growth factor-induced Flk-1 activation as well as downstream signaling pathways that involve c-Src, Akt, eNOS, FAK, and ERK1/2. These in vitro data suggest potential sites of the apoE dipeptide inhibition that could occur in vivo.This is the first evidence that a synthetic dimer peptide mimicking human apoE has anti-angiogenesis functions and could be an anti-tumor drug candidate.

  14. Low plasma apolipoprotein A-I level is not a reliable marker of fibrosis in children with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Mukadder Ayse Selimoglu; Rasit Vural Yagcl; Gül Yüce

    2004-01-01

    AIM: To evaluate the clinical value of plasma apolipoprotein A-I (Apo A-I) as a marker of fibrosis in children with chronic hepatitis B (CHB).METHODS: Liver biopsy specimens from 49 children with CHB were evaluated by using Knodell index. Plasma Apo A-I level was measured after 12-h fasting. Student's ttest,Spearman's correlation test and receptor-operating characteristic (ROC) curve were used for statistical evaluation.RESULTS: Mean Apo A-I level of the patients was not different from that of controls (P>0.05). Six (8.7%) children had fibrosis score of more than 2 (severe fibrosis). No difference in the level of mean plasma Apo A-I was found among children with and without severe fibrosis (P>0.05). No correlation between Apo A-I level and fibrosis scores was found (P>0.05).The area under the ROC curve was 0.407±0.146 (P>0.05).CONCLUSIOM: Severe fibrosis is not common in children with CHB and plasma Apo A-I level is not a reliable indicator of fibrosis.

  15. Structural and functional characterization of human apolipoprotein E 72-166 peptides in both aqueous and lipid environments

    Directory of Open Access Journals (Sweden)

    Chou Chi-Yuan

    2011-01-01

    Full Text Available Abstract Backgrounds There are three apolipoprotein E (apoE isoforms involved in human lipid homeostasis. In the present study, truncated apoE2-, apoE3- and apoE4-(72-166 peptides that are tailored to lack domain interactions are expressed and elucidated the structural and functional consequences. Methods & Results Circular dichroism analyses indicated that their secondary structure is still well organized. Analytical ultracentrifugation analyses demonstrated that apoE-(72-166 produces more complicated species in PBS. All three isoforms were significantly dissociated in the presence of dihexanoylphosphatidylcholine. Dimyristoylphosphatidylcholine turbidity clearance assay showed that apoE4-(72-166 maintains the highest lipid-binding capacity. Finally, only apoE4-(72-166 still maintained significant LDL receptor binding ability. Conclusions Overall, apoE4-(72-166 peptides displayed a higher lipid-binding and comparable receptor-binding ability as to full-length apoE. These findings provide the explanation of diverged functionality of truncated apoE isoforms.

  16. Demographic and Lifestyle Characteristics, but Not Apolipoprotein E Genotype, Are Associated with Intelligence among Young Chinese College Students.

    Directory of Open Access Journals (Sweden)

    Xiao-Fen Chen

    Full Text Available Intelligence is an important human feature that strongly affects many life outcomes, including health, life-span, income, educational and occupational attainments. People at all ages differ in their intelligence but the origins of these differences are much debated. A variety of environmental and genetic factors have been reported to be associated with individual intelligence, yet their nature and contribution to intelligence differences have been controversial.To investigate the contribution of apolipoprotein E (APOE genotype, which is associated with the risk for Alzheimer's disease, as well as demographic and lifestyle characteristics, to the variation in intelligence.A total of 607 Chinese college students aged 18 to 25 years old were included in this prospective observational study. The Chinese revision of Wechsler Adult Intelligence Scale (the fourth edition, short version was used to determine the intelligence level of participants. Demographic and lifestyle characteristics data were obtained from self-administered questionnaires.No significant association was found between APOE polymorphic alleles and different intelligence quotient (IQ measures. Interestingly, a portion of demographic and lifestyle characteristics, including age, smoking and sleep quality were significantly associated with different IQ measures.Our findings indicate that demographic features and lifestyle characteristics, but not APOE genotype, are associated with intelligence measures among young Chinese college students. Thus, although APOE ε4 allele is a strong genetic risk factor for Alzheimer's disease, it does not seem to impact intelligence at young ages.

  17. Characterization of five new mutants in the carboxyl-terminal domain of human apolipoprotein E: No cosegregation with severe hyperlipidemia

    Energy Technology Data Exchange (ETDEWEB)

    Maagdenberg, A.M.J.M. van den; Bruijn, I.H. de; Hofker, M.H.; Frants, R.R. (Leiden Univ. (Netherlands)); Knijff, P. de; Smelt, A.H.M.; Leuven, J.A.G.; van' t Hooft, F.; Assmann, G.; Havekes, L.M. (Univ. Hospital, Leiden (Netherlands)); Weng, Wei; Funke, H. (Westfalische Wilhelms-Universitaet, Muester (Germany))

    1993-05-01

    Assessment of the apolipoprotein E (apoE) phenotype by isoelectric focusing of both hyperlipidemic and normolipidemic individuals identified five new variants. All mutations were confined to the downstream part of the APOE gene by using denaturing gradient gel electrophoresis (DGGE). Sequence analysis revealed five new mutations causing unique amino acid substitutions in the carboxyl-terminal part of the protein containing the putative lipid-binding domain. Three hyperlipoproteinemic probands were carriers of the APOE*2(Va1236[r arrow]Glu) allele, the APOE*3(Cys112-Arg; Arg251[r arrow]Gly) allele, or the APOE*1(Arg158[r arrow]Cys; Leu252[r arrow]Glu) allele. DGGE of the region encoding the receptor-binding domain was useful for haplotyping the mutations at codons 112 and 158. Family studies failed to demonstrate cosegregation between the new mutations and severe hyperlipoproteinemia, although a number of carriers for the APOE*3(Cys112[r arrow]Arg; Arg251[r arrow]Gly) allele and the APOE*1(Arg158-Cys; Leu252[r arrow]Glu) allele expressed hypertriglyceridemia and/ or hypercholesterolemia. Two other mutant alleles, APOE*4[sup [minus

  18. Pharmacogenetics of apolipoprotein E gene during lipid-lowering therapy: lipid levels and prevention of coronary heart disease.

    Science.gov (United States)

    Nieminen, Tuomo; Kähönen, Mika; Viiri, Leena E; Grönroos, Paula; Lehtimäki, Terho

    2008-10-01

    A non-optimal plasma concentration of lipids is among the major modifiable risk factors of atherosclerosis. Therefore, the prevention of cardiovascular disease by means of lipid-lowering therapy with statins and other agents is of great importance for patient groups where a lifestyle change, for example, diet modification, does not lead to adequately reduced lipid levels. The response of low-density-lipoprotein cholesterol (LDL-C) levels to statin therapy is highly variable. This is partly attributed to hereditary variation in genes involved in pharmacokinetics, pharmacodynamics and lipid metabolism. The pharmacogenetics of lipid-lowering therapy have been investigated for more than 40 different genes. The gene for apolipoprotein E (APOE) has been the most frequently studied, particularly regarding the epsilon2/epsilon3/epsilon4 polymorphism. Those with the epsilon4 allele seem to have the poorest and those with the epsilon2 allele the strongest response to statins with regards to LDL-C levels. In addition, the epsilon2 carriers may reach the LDL-C treatment goals more frequently than epsilon4 carriers. Few studies have investigated the interaction of the APOE epsilon2/epsilon3/epsilon4 polymorphism and lipid-lowering therapy in relation to the course of coronary heart disease; the results are contradictory and so far inconclusive. This review summarizes the pharmacogenetic findings related to the influence of APOE gene variation on lipid responses and the prevention of coronary heart disease during lipid-lowering therapy. PMID:18855536

  19. Increased prothrombin, apolipoprotein A-IV, and haptoglobin in the cerebrospinal fluid of patients with Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Yen-Chu Huang

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disease caused by an unstable CAG trinucleotide repeat expansion. The need for biomarkers of onset and progression in HD is imperative, since currently reliable outcome measures are lacking. We used two-dimensional electrophoresis and mass spectrometry to analyze the proteome profiles in cerebrospinal fluid (CSF of 6 pairs of HD patients and controls. Prothrombin, apolipoprotein A-IV (Apo A-IV and haptoglobin were elevated in CSF of the HD patients in comparison with the controls. We used western blot as a semi-quantified measurement for prothrombin and Apo A-IV, as well as enzyme linked immunosorbent assay (ELISA for measurement of haptoglobin, in 9 HD patients and 9 controls. The albumin quotient (Qalb, a marker of blood-brain barrier (BBB function, was not different between the HD patients and the controls. The ratios of CSF prothrombin/albumin (prothrombin/Alb and Apo A-IV/albumin (Apo A-IV/Alb, and haptoglobin level were significantly elevated in HD. The ratio of CSF prothrombin/Alb significantly correlated with the disease severity assessed by Unified Huntington's Disease Rating Scale (UHDRS. The results implicate that increased CSF prothrombin, Apo A-IV, and haptoglobin may be involved in pathogenesis of HD and may serve as potential biomarkers for HD.

  20. Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes.

    Directory of Open Access Journals (Sweden)

    Casey R Dorr

    Full Text Available Apolipoprotein L1 gene (APOL1 G1 and G2 renal-risk variants, common in populations with recent African ancestry, are strongly associated with non-diabetic nephropathy, end-stage kidney disease, and shorter allograft survival in deceased-donor kidneys (autosomal recessive inheritance. Circulating APOL1 protein is synthesized primarily in the liver and hydrodynamic gene delivery of APOL1 G1 and G2 risk variants has caused hepatic necrosis in a murine model.To evaluate the impact of these variants in liver transplantation, this multicenter study investigated the association of APOL1 G1 and G2 alleles in deceased African American liver donors with allograft survival. Transplant recipients were followed for liver allograft survival using data from the Scientific Registry of Transplant Recipients.Of the 639 liver donors evaluated, 247 had no APOL1 risk allele, 300 had 1 risk allele, and 92 had 2 risk alleles. Graft failure assessed at 15 days, 6 months, 1 year and total was not significantly associated with donor APOL1 genotype (p-values = 0.25, 0.19, 0.67 and 0.89, respectively.In contrast to kidney transplantation, deceased-donor APOL1 G1 and G2 risk variants do not significantly impact outcomes in liver transplantation.

  1. Apolipoprotein AI tertiary structures determine stability and phospholipid-binding activity of discoidal high-density lipoprotein particles of different sizes

    OpenAIRE

    Chen, Bin; Ren, Xuefeng; Neville, Tracey; Jerome, W. Gray; Hoyt, David W.; Sparks, Daniel; Ren, Gang; Wang, Jianjun

    2009-01-01

    Human high-density lipoprotein (HDL) plays a key role in the reverse cholesterol transport pathway that delivers excess cholesterol back to the liver for clearance. In vivo, HDL particles vary in size, shape and biological function. The discoidal HDL is a 140–240 kDa, disk-shaped intermediate of mature HDL. During mature spherical HDL formation, discoidal HDLs play a key role in loading cholesterol ester onto the HDL particles by activating the enzyme, lecithin:cholesterol acyltransferase (LC...

  2. Apolipoprotein A-I Mimetic Peptide D-4F Reduces Cardiac Hypertrophy and Improves Apolipoprotein A-I-Mediated Reverse Cholesterol Transport From Cardiac Tissue in LDL Receptor-null Mice Fed a Western Diet.

    Science.gov (United States)

    Han, Jie; Zhang, Song; Ye, Ping; Liu, Yong-Xue; Qin, Yan-Wen; Miao, Dong-Mei

    2016-05-01

    Epidemiological studies have suggested that hypercholesterolemia is an independent determinant of increased left ventricular (LV) mass. Because high-density lipoprotein and its major protein apolipoprotein A-I (apoA-I) mediate reverse cholesterol transport (RCT) and have cardiac protective effects, we hypothesized that the apoA-I mimetic peptide D-4F could promote RCT in cardiac tissue and decrease cardiac hypertrophy induced by hypercholesterolemia. Low-density lipoprotein receptor-null mice were fed by a Western diet for 18 weeks and then randomized to receive water, or D-4F 0.3 mg/mL, or D-4F 0.5 mg/mL added to drinking water for 6 weeks. After D-4F administration, an increase in high-density lipoprotein cholesterol and a decrease in low-density lipoprotein cholesterol, total cholesterol, and triglyceride in a trend toward dose-responsivity were found in cardiac tissue. Ultrasound biomicroscopy revealed a reduction in LV posterior wall end-diastolic dimension, and an increase in mitral valve E/A ratio and LV ejection fraction. Hematoxylin-eosin staining showed reduced LV wall thickness and myocardial cell diameter. The protein levels of ABCA1 and LXRα were elevated in cardiac tissue of D-4F treated mice compared with the controls (P < 0.05). These results demonstrated that D-4F treatment reduced cardiac hypertrophy, and improved cardiac performance in low-density lipoprotein receptor-null mice fed a Western diet, presumably through the LXRα-ABCA1 pathway associated with enhanced myocardial RCT. PMID:26828321

  3. Trapped particle stability for the kinetic stabilizer

    Science.gov (United States)

    Berk, H. L.; Pratt, J.

    2011-08-01

    A kinetically stabilized axially symmetric tandem mirror (KSTM) uses the momentum flux of low-energy, unconfined particles that sample only the outer end-regions of the mirror plugs, where large favourable field-line curvature exists. The window of operation is determined for achieving magnetohydrodynamic (MHD) stability with tolerable energy drain from the kinetic stabilizer. Then MHD stable systems are analysed for stability of the trapped particle mode. This mode is characterized by the detachment of the central-cell plasma from the kinetic-stabilizer region without inducing field-line bending. Stability of the trapped particle mode is sensitive to the electron connection between the stabilizer and the end plug. It is found that the stability condition for the trapped particle mode is more constraining than the stability condition for the MHD mode, and it is challenging to satisfy the required power constraint. Furthermore, a severe power drain may arise from the necessary connection of low-energy electrons in the kinetic stabilizer to the central region.

  4. Plutonium inventories for stabilization and stabilized materials

    Energy Technology Data Exchange (ETDEWEB)

    Williams, A.K.

    1996-05-01

    The objective of the breakout session was to identify characteristics of materials containing plutonium, the need to stabilize these materials for storage, and plans to accomplish the stabilization activities. All current stabilization activities are driven by the Defense Nuclear Facilities Safety Board Recommendation 94-1 (May 26, 1994) and by the recently completed Plutonium ES&H Vulnerability Assessment (DOE-EH-0415). The Implementation Plan for accomplishing stabilization of plutonium-bearing residues in response to the Recommendation and the Assessment was published by DOE on February 28, 1995. This Implementation Plan (IP) commits to stabilizing problem materials within 3 years, and stabilizing all other materials within 8 years. The IP identifies approximately 20 metric tons of plutonium requiring stabilization and/or repackaging. A further breakdown shows this material to consist of 8.5 metric tons of plutonium metal and alloys, 5.5 metric tons of plutonium as oxide, and 6 metric tons of plutonium as residues. Stabilization of the metal and oxide categories containing greater than 50 weight percent plutonium is covered by DOE Standard {open_quotes}Criteria for Safe Storage of Plutonium Metals and Oxides{close_quotes} December, 1994 (DOE-STD-3013-94). This standard establishes criteria for safe storage of stabilized plutonium metals and oxides for up to 50 years. Each of the DOE sites and contractors with large plutonium inventories has either started or is preparing to start stabilization activities to meet these criteria.

  5. Trapped particle stability for the kinetic stabilizer

    International Nuclear Information System (INIS)

    A kinetically stabilized axially symmetric tandem mirror (KSTM) uses the momentum flux of low-energy, unconfined particles that sample only the outer end-regions of the mirror plugs, where large favourable field-line curvature exists. The window of operation is determined for achieving magnetohydrodynamic (MHD) stability with tolerable energy drain from the kinetic stabilizer. Then MHD stable systems are analysed for stability of the trapped particle mode. This mode is characterized by the detachment of the central-cell plasma from the kinetic-stabilizer region without inducing field-line bending. Stability of the trapped particle mode is sensitive to the electron connection between the stabilizer and the end plug. It is found that the stability condition for the trapped particle mode is more constraining than the stability condition for the MHD mode, and it is challenging to satisfy the required power constraint. Furthermore, a severe power drain may arise from the necessary connection of low-energy electrons in the kinetic stabilizer to the central region.

  6. Metformin reduces the endotoxin-induced down-regulation of apolipoprotein E gene expression in macrophages

    International Nuclear Information System (INIS)

    The atheroprotective role of macrophage-derived apolipoprotein E (apoE) is well known. Our previous reports demonstrated that inflammatory stress down-regulates apoE expression in macrophages, aggravating atherogenesis. Metformin, extensively used as an anti-diabetic drug, has also anti-inflammatory properties, and thus confers vascular protection. In this study, we questioned whether metformin could have an effect on apoE expression in macrophages in normal conditions or under lipopolysaccharide (LPS)-induced stress. The results showed that metformin slightly increases the apoE expression only at high doses (5–10 mM). Low doses of metformin (1–3 mM) significantly reduce the LPS down-regulatory effect on apoE expression in macrophages. Our experiments demonstrated that LPS-induced NF-κB binds to the macrophage-specific distal regulatory element of apoE gene, namely to the multienhancer 2 (ME.2) and its 5′-deletion fragments. The NF-κB binding on ME.2 and apoE promoter has a down-regulatory effect. In addition, data revealed that metformin impairs NF-κB nuclear translocation, and thus, improves the apoE levels in macrophages under inflammatory stress. The positive effect of metformin in the inflammatory states, its clinical safety and low cost, make this drug a potential adjuvant in the therapeutic strategies for atherosclerosis. - Highlights: • High doses of metformin slightly increase apoE expression in macrophages. • Low doses of metformin up-regulate apoE gene in endotoxin-stressed macrophages. • Metformin reduces the negative effect of LPS on apoE expression by NF-κB inhibition

  7. Palmitic acid suppresses apolipoprotein M gene expression via the pathway of PPARβ/δ in HepG2 cells

    International Nuclear Information System (INIS)

    Highlights: • Palmitic acid significantly inhibited APOM gene expression in HepG2 cells. • Palmitic acid could obviously increase PPARB/D mRNA levels in HepG2 cells. • PPARβ/δ antagonist, GSK3787, had no effect on APOM expression. • GSK3787 could reverse the palmitic acid-induced down-regulation of APOM expression. • Palmitic acid induced suppression of APOM expression is mediated via the PPARβ/δ pathway. - Abstract: It has been demonstrated that apolipoprotein M (APOM) is a vasculoprotective constituent of high density lipoprotein (HDL), which could be related to the anti-atherosclerotic property of HDL. Investigation of regulation of APOM expression is of important for further exploring its pathophysiological function in vivo. Our previous studies indicated that expression of APOM could be regulated by platelet activating factor (PAF), transforming growth factors (TGF), insulin-like growth factor (IGF), leptin, hyperglycemia and etc., in vivo and/or in vitro. In the present study, we demonstrated that palmitic acid could significantly inhibit APOM gene expression in HepG2 cells. Further study indicated neither PI-3 kinase (PI3K) inhibitor LY294002 nor protein kinase C (PKC) inhibitor GFX could abolish palmitic acid induced down-regulation of APOM expression. In contrast, the peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) antagonist GSK3787 could totally reverse the palmitic acid-induced down-regulation of APOM expression, which clearly demonstrates that down-regulation of APOM expression induced by palmitic acid is mediated via the PPARβ/δ pathway

  8. Regulation of apolipoprotein A-I gene expression in Hep G2 cells depleted of Cu by cupruretic tetramine.

    Science.gov (United States)

    Wu, J Y; Zhang, J J; Wang, Y; Reaves, S K; Wang, Y R; Lei, P P; Lei, K Y

    1997-10-01

    Studies were designed to examine the regulation of apolipoprotein (apo) A-I gene expression in Cu-depleted Hep G2 cells. The cupruretic chelator N,N'-bis(2-aminoethyl)-1,3-propanediamine 4 HCl (2,3,2-tetramine or TETA) was used to maintain a 77% reduction in cellular Cu in Hep G2 cells. After two passages of TETA treatment, the relative abundance of apoA-I mRNA was elevated 52%. In TETA-treated cells, the rate of apoA-I mRNA decay measured by an actinomycin D chase study was accelerated 108%, and the synthesis of apoA-I mRNA determined by a nuclear runoff assay was enhanced 2.5-fold in TETA-treated cells. All of those changes could be reverted toward the control values with Cu supplementation for only 2 days. In transient transfection assays, a 26.7% increase in chloramphenicol O-acetyltransferase (CAT) activity for the reporter construct -256AI-CAT was observed in the treated cells. However, the ability of apoA-I regulatory protein 1 (ARP-1) to repress the CAT activity was not affected by the depressed Cu status. In addition, gel retardation experiments demonstrated that Cu depletion enhanced the binding of hepatocyte nuclear factor 4 (HNF-4) and other undefined nuclear factors to oligonucleotides containing site A, one of three regulatory sites of the apoA-I gene promoter. Moreover, the relative abundance of HNF-4 mRNA was increased 58% in the Cu-depleted cells. Thus the observed increase in apoA-I gene transcription may be mediated mostly by an elevated level of the regulatory factor, HNF-4. In summary, the present findings established the mechanism by which a depressed cellular Cu status can enhance apoA-I mRNA production and subsequently increase apoA-I synthesis. PMID:9357782

  9. Apolipoprotein E Variation at the Sequence Haplotype Level: Implications for the Origin and Maintenance of a Major Human Polymorphism

    Science.gov (United States)

    Fullerton, Stephanie M.; Clark, Andrew G.; Weiss, Kenneth M.; Nickerson, Deborah A.; Taylor, Scott L.; Stengård, Jari H.; Salomaa, Veikko; Vartiainen, Erkki; Perola, Markus; Boerwinkle, Eric; Sing, Charles F.

    2000-01-01

    Three common protein isoforms of apolipoprotein E (apoE), encoded by the ε2, ε3, and ε4 alleles of the APOE gene, differ in their association with cardiovascular and Alzheimer's disease risk. To gain a better understanding of the genetic variation underlying this important polymorphism, we identified sequence haplotype variation in 5.5 kb of genomic DNA encompassing the whole of the APOE locus and adjoining flanking regions in 96 individuals from four populations: blacks from Jackson, MS (n=48 chromosomes), Mayans from Campeche, Mexico (n=48), Finns from North Karelia, Finland (n=48), and non-Hispanic whites from Rochester, MN (n=48). In the region sequenced, 23 sites varied (21 single nucleotide polymorphisms, or SNPs, 1 diallelic indel, and 1 multiallelic indel). The 22 diallelic sites defined 31 distinct haplotypes in the sample. The estimate of nucleotide diversity (site-specific heterozygosity) for the locus was 0.0005±0.0003. Sequence analysis of the chimpanzee APOE gene showed that it was most closely related to human ε4-type haplotypes, differing from the human consensus sequence at 67 synonymous (54 substitutions and 13 indels) and 9 nonsynonymous fixed positions. The evolutionary history of allelic divergence within humans was inferred from the pattern of haplotype relationships. This analysis suggests that haplotypes defining the ε3 and ε2 alleles are derived from the ancestral ε4s and that the ε3 group of haplotypes have increased in frequency, relative to ε4s, in the past 200,000 years. Substantial heterogeneity exists within all three classes of sequence haplotypes, and there are important interpopulation differences in the sequence variation underlying the protein isoforms that may be relevant to interpreting conflicting reports of phenotypic associations with variation in the common protein isoforms. PMID:10986041

  10. Measurement of apolipoprotein mRNA by DNA-excess solution hybridization with single-stranded probes

    International Nuclear Information System (INIS)

    DNA-excess solution hybridization provides the greatest sensitivity and reliability for mRNA measurement. This method is analogous to a receptor binding assay in which the receptor (the mRNA) is reacted to completion with an excess of ligand (single-strand cDNA). In practice, total cellular RNA is incubated with an excess of radiolabeled single-stranded probe complimentary to a specific mRNA. Probe which remains unhybridized is subsequently digested with S1 nuclease, a single-strand-specific nuclease. Hybridized probe is collected by acid precipitation and measured by scintillation spectrometry. This procedure has several advantages. First, the assay is carried out in solution such that all the mRNA and probe are available to react. Second, the reaction proceeds to completion and within broad limits is independent of factors that can influence hybridization kinetics. Third, this method provides absolute values for mRNA measurements. Fourth, the assay is exquisitely sensitive. Routine sensitivity is at the level of 1 mRNA molecule/cell, and the sensitivity can be greatly increased if necessary. Fifth, the assay requires small amounts of total cellular RNA. Sixth, the assay procedure itself is very simple as is the preparation of single-stranded probe. Until recently, the preparation of such probes has been difficult. However, recent developments in labeling techniques and the use of single-stranded cloning vectors have made the preparation of probes routine. The authors describe here the hybridization assay and two methods for the preparation of high specific activity single-stranded probes. These methods are used routinely in this laboratory for the measurement of mRNAs for human apolipoprotein (apo)E and apoA-I and for avian apo II and vitellogenin

  11. Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of 56Fe Irradiation on the Brain

    International Nuclear Information System (INIS)

    Purpose: In humans, apolipoprotein E (apoE) is encoded by three major alleles (ε2, ε3, and ε4) and, compared to apoE3, apoE4 increases the risk of developing Alzheimer disease and cognitive impairments following various environmental challenges. Exposure to irradiation, including that of 56Fe, during space missions poses a significant risk to the central nervous system, and apoE isoform might modulate this risk. Methods and Materials: We investigated whether apoE isoform modulates hippocampus-dependent cognitive performance starting 2 weeks after 56Fe irradiation. Changes in reactive oxygen species (ROS) can affect cognition and are induced by irradiation. Therefore, after cognitive testing, we assessed hippocampal ROS levels in ex vivo brain slices, using the ROS-sensitive fluorescent probe, dihydroethidium (DHE). Brain levels of 3-nitrotyrosine (3-NT), CuZn superoxide dismutase (CuZnSOD), extracellular SOD, and apoE were assessed using Western blotting analysis. Results: In the water maze, spatial memory retention was impaired by irradiation in apoE2 and apoE4 mice but enhanced by irradiation in apoE3 mice. Irradiation reduced DHE-oxidation levels in the enclosed blade of the dentate gyrus and levels of 3-NT and CuZnSOD in apoE2 but not apoE3 or apoE4 mice. Finally, irradiation increased apoE levels in apoE3 but not apoE2 or apoE4 mice. Conclusions: The short-term effects of 56Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial memory retention are apoE isoform-dependent.

  12. Long-Term Effects of 56Fe Irradiation on Spatial Memory of Mice: Role of Sex and Apolipoprotein E Isoform

    International Nuclear Information System (INIS)

    Purpose: To assess whether the effects of cranial 56Fe irradiation on the spatial memory of mice in the water maze are sex and apolipoprotein E (apoE) isoform dependent and whether radiation-induced changes in spatial memory are associated with changes in the dendritic marker microtubule-associated protein 2 (MAP-2) and the presynaptic marker synaptophysin. Methods and Materials: Two-month-old male and female mice expressing human apoE3 or apoE4 received either a 3-Gy dose of cranial 56Fe irradiation (600 MeV/amu) or sham irradiation. Mice were tested in a water maze task 13 months later to assess effects of irradiation on spatial memory retention. After behavioral testing, the brain tissues of these mice were analyzed for synaptophysin and MAP-2 immunoreactivity. Results: After irradiation, spatial memory retention of apoE3 female, but not male, mice was impaired. A general genotype deficit in spatial memory was observed in sham-irradiated apoE4 mice. Strikingly, irradiation prevented this genotype deficit in apoE4 male mice. A similar but nonsignificant trend was observed in apoE4 female mice. Although there was no change in MAP-2 immunoreactivity after irradiation, synaptophysin immunoreactivity was increased in irradiated female mice, independent of genotype. Conclusions: The effects of 56Fe irradiation on the spatial memory retention of mice are critically influenced by sex, and the direction of these effects is influenced by apoE isoform. Although in female mice synaptophysin immunoreactivity provides a sensitive marker for effects of irradiation, it cannot explain the apoE genotype-dependent effects of irradiation on the spatial memory retention of the mice.

  13. Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of {sup 56}Fe Irradiation on the Brain

    Energy Technology Data Exchange (ETDEWEB)

    Haley, Gwendolen E. [Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR (United States); Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR (United States); Villasana, Laura; Dayger, Catherine; Davis, Matthew J. [Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR (United States); Raber, Jacob, E-mail: raberj@ohsu.edu [Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR (United States); Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR (United States); Department of Neurology, Oregon Health and Science University, Portland, OR (United States)

    2012-11-01

    Purpose: In humans, apolipoprotein E (apoE) is encoded by three major alleles ({epsilon}2, {epsilon}3, and {epsilon}4) and, compared to apoE3, apoE4 increases the risk of developing Alzheimer disease and cognitive impairments following various environmental challenges. Exposure to irradiation, including that of {sup 56}Fe, during space missions poses a significant risk to the central nervous system, and apoE isoform might modulate this risk. Methods and Materials: We investigated whether apoE isoform modulates hippocampus-dependent cognitive performance starting 2 weeks after {sup 56}Fe irradiation. Changes in reactive oxygen species (ROS) can affect cognition and are induced by irradiation. Therefore, after cognitive testing, we assessed hippocampal ROS levels in ex vivo brain slices, using the ROS-sensitive fluorescent probe, dihydroethidium (DHE). Brain levels of 3-nitrotyrosine (3-NT), CuZn superoxide dismutase (CuZnSOD), extracellular SOD, and apoE were assessed using Western blotting analysis. Results: In the water maze, spatial memory retention was impaired by irradiation in apoE2 and apoE4 mice but enhanced by irradiation in apoE3 mice. Irradiation reduced DHE-oxidation levels in the enclosed blade of the dentate gyrus and levels of 3-NT and CuZnSOD in apoE2 but not apoE3 or apoE4 mice. Finally, irradiation increased apoE levels in apoE3 but not apoE2 or apoE4 mice. Conclusions: The short-term effects of {sup 56}Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial memory retention are apoE isoform-dependent.

  14. Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study.

    Science.gov (United States)

    Caselli, R J; Osborne, D; Reiman, E M; Hentz, J G; Barbieri, C J; Saunders, A M; Hardy, J; Graff-Radford, N R; Hall, G R; Alexander, G E

    2001-08-15

    In a previous cross-sectional study of 100 asymptomatic individuals aged 49-69, we reported age-related decline in immediate and delayed memory that was steeper in apolipoprotein E (apoE)-e4/4 homozygotes than in members of other genetic subgroups. These findings were preliminarily based upon the statistical problem of multiple comparisons. We therefore sought to replicate these findings in a new cohort. From 1998 to 2000, 80 asymptomatic residents of Maricopa County, AZ were recruited through newspaper ads. 20 apoE-e4/4 homozygotes, 20 e3/4 heterozygotes, and 40 e4 noncarriers were matched (1:1:2) by age, gender, and years of education. All had normal neurologic and psychiatric examinations, including Folstein minimental status exam (MMSE) and Hamilton depression scale, and underwent a battery of neuropsychological tests identical to those in our previous study. The groups were well-matched for age (55.9+/-5.9 years), gender (60% women), and education (15.9+/-2.2 years), and were demographically similar to our previous cohort. Complex figure test recall was lower in e3/4 heterozygotes than noncarriers, but there was no significant difference between e4/4 homozygotes and noncarriers. There were no other significant differences in mean test scores between groups, but Wechsler adult intelligence scale-revised (WAIS-R) digit span showed a significant negative correlation with age in the e4/4 homozygote group relative to e4 noncarriers (p=0.008) as we had found in our previous study. In conclusion, we found a significant negative correlation of WAIS-R digit span with age in apoE-e4/4 homozygotes relative to e4 noncarriers in two separate cohorts, possibly reflecting an age-related effect on frontal lobe function in this genetic subgroup. PMID:11535238

  15. Effects of radiation and apolipoprotein E on lipid profile among workers of nuclear power plants in Korea

    International Nuclear Information System (INIS)

    Complete text of publication follows. Several studies reported that the radiation was positively related to fatty liver, low HDL cholesterol, and hypertriglyceridemia. Genetic polymorphism affect prevalence of chronic disease by molecular epidemiology studies. Apolipoprotein E is an important genetic determinant of cardiovascular disease (CVD), namely through its influence on lipid metabolism. Thus, we investigated whether radiation and apo E polymorphism, and environmental factors contribute to the lipid profile in workers of nuclear power plants in Korea. DNA was extracted from the whole blood of 6896 study subjects (6357 males and 359 females), and apo E polymorphism was investigated using PCR. Plasma lipid profiles were measured by standardized enzymatic procedures and radiation dose was measured by the thermoluminescence dosemeter (TLD). Environmental factors such as exercise, smoking were measured from health management database of KHNP. Total of 6802 subjects (aged 20-58) were investigated and radiation exposure dose was 168.51±463.94 mSv in the recent 1-year dose and 248.24±559.21 mSv in the total accumulative dose. In addition, Apo E polymorphism was associated with significant differences in total cholesterol, HDL cholesterol, radiation dose, AI but others no significant. The multiple regression model showed that total cholesterol was positively correlated with age, SBP, BMI, AI, fasting glucose. HDL cholesterol was negatively correlated with AI. LDL cholesterol was positively correlated with age, BMI, fasting glucose. And triglyceride was significantly correlated in the BMI, AI, somking dose, vegetables but others no significant. Metabolic syndrome did not show any relation to the others; only age, SBP, DBP, BMI, fasting glucose, HOMA-IR influenced. However, there was no significant association between radiation dose and lipid profile. In conclusion, Apo E and well-known variables such as SBP, BMI were significantly associated with lipid profile level

  16. Apolipoprotein E mRNA expression in mononuclear cells from normolipidemic and hypercholesterolemic individuals treated with atorvastatin

    Directory of Open Access Journals (Sweden)

    Cerda Alvaro

    2011-11-01

    Full Text Available Abstract Background Apolipoprotein E (apoE is a key component of the lipid metabolism. Polymorphisms at the apoE gene (APOE have been associated with cardiovascular disease, lipid levels and lipid-lowering response to statins. We evaluated the effects on APOE expression of hypercholesterolemia, APOE ε2/ε3/ε4 genotypes and atorvastatin treatment in Brazilian individuals. The relationship of APOE genotypes and plasma lipids and atorvastatin response was also tested in this population. Methods APOE ε2/ε3/ε4 and plasma lipids were evaluated in 181 normolipidemic (NL and 181 hypercholesterolemic (HC subjects. HC individuals with indication for lowering-cholesterol treatment (n = 141 were treated with atorvastatin (10 mg/day/4-weeks. APOE genotypes and APOE mRNA in peripheral blood mononuclear cells (PBMC were analyzed by TaqMan real time PCR. Results HC had lower APOE expression than NL group (p APOE expression showed higher plasma total and LDL cholesterol and apoB, as well as higher apoAI (p APOE genotypes did not affect APOE expression and atorvastatin response. Atorvastatin treatment do not modify APOE expression, however those individuals without LDL cholesterol goal achievement after atorvastatin treatment according to the IV Brazilian Guidelines for Dyslipidemia and Atherosclerosis Prevention had lower APOE expression than patients with desirable response after the treatment (p Conclusions APOE expression in PBMC is modulated by hypercholesterolemia and the APOE mRNA level regulates the plasma lipid profile. Moreover the expression profile is not modulated neither by atorvastatin nor APOE genotypes. In our population, APOE ε2 allele confers protection against hypercholesterolemia and a less atherogenic lipid profile. Moreover, low APOE expression after treatment of patients with poor response suggests a possible role of APOE level in atorvastatin response.

  17. Novel molecular imaging of atherosclerosis with gallium-68-labeled apolipoprotein A-I mimetic peptide and positron emission tomography

    International Nuclear Information System (INIS)

    High-density lipoprotein (HDL) plays a major role in reverse cholesterol transport. Many researchers have been working to enhance the biochemical function of HDL for use in therapy. Although HDL therapy using injections of apolipoprotein (apo)-A-I mimetics, apo A-IMilano or full-length apo A-I is dramatically effective, it is still unclear whether apo A-I or apo A-I mimetics actually enter atherosclerotic plaque and remove cholesterol from the lipid burden. We synthesized a novel 24-amino acid apo A-I mimetic peptide (known as Fukuoka University apo A-I mimetic peptide (FAMP)) that potently removes cholesterol via specific adenosine 5'-triphosphate (ATP)-binding cassette transporter A1. We then investigated the potential of FAMP to image developing plaque lesions in vivo. FAMP was modified with 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with gallium-68 (68Ga) for noninvasive positron emission tomography (PET) in an animal model (familial hypercholesterolemic myocardial infarction-prone rabbits: Watanabe heritable hyperlipidemic (WHHL-MI)) with atherosclerotic lesions. The 68Ga-DOTA-FAMP was dramatically taken up by atherosclerotic tissues in the blood vessels and aorta of WHHL-MI rabbits, but not the control rabbits. An apo A-I mimetic peptide with 68Ga-DOTA is a promising candidate diagnostic tracer for PET imaging of the atherosclerotic lipid burden and may contribute to the development of a tool for the diagnosis of plaque with PET. (author)

  18. A case–control study on the effect of Apolipoprotein E genotypes on gastric cancer risk and progression

    Directory of Open Access Journals (Sweden)

    De Feo Emma

    2012-10-01

    Full Text Available Abstract Background Apolipoprotein E (ApoE is a multifunctional protein playing both a key role in the metabolism of cholesterol and triglycerides, and in tissue repair and inflammation. The ApoE gene (19q13.2 has three major isoforms encoded by ε2, ε3 and ε4 alleles with the ε4 allele associated with hypercholesterolemia and the ε2 allele with the opposite effect. An inverse relationship between cholesterol levels and gastric cancer (GC has been previously reported, although the relationship between apoE genotypes and GC has not been explored so far. Methods One hundred and fifty-six gastric cancer cases and 444 hospital controls were genotyped for apoE polymorphism (ε2, ε3, ε4 alleles. The relationship between GC and putative risk factors was measured using the adjusted odds ratios (ORs and their 95% confidence intervals (CIs from logistic regression analysis. A gene-environment interaction analysis was performed. The effect of the apoE genotypes on survival from GC was explored by a Kaplan–Meier analysis and Cox proportional hazard regression model. Results Subjects carrying at least one apoE ε2 allele have a significant 60% decrease of GC risk (OR=0.40, 95% CI: 0.19 – 0.84 compared with ε3 homozygotes. No significant interaction emerged between the ε4 or ε2 allele and environmental exposures, nor ε2 or ε4 alleles affected the median survival times, even after correcting for age, gender and stadium. Conclusions Our study reports for the first time a protective effect of the ε2 allele against GC, that might be partly attributed to the higher antioxidant properties of ε2 compared with the ε3 or ε4 alleles. Given the study’s sample size, further studies are required to confirm our findings.

  19. Identification, molecular characterization, and cellular studies of an apolipoprotein E mutant (E1) in three unrelated families with hyperlipidemia.

    Science.gov (United States)

    Miller, D B; Hegele, R A; Wolfe, B M; Huff, M W

    1995-03-01

    Remnants of triglyceride-rich lipoproteins accumulate in plasma of subjects with type III hyperlipoproteinemia (HLP) due to defective clearance by hepatic receptors. Although most subjects with type III HLP are homozygous for apolipoprotein (apo) E2 (arg158-->cys, R158C), a variant that binds defectively to cell surface receptors, some individuals with type III HLP have rare mutations of apo E. We identified six subjects from three families with type III HLP who had either an apo E3/1 or E4/1 phenotype by isoelectric focusing. Using DNA restriction isotyping with HhaI, all six subjects were determined to have only one apo E allele encoding cys158 and the other encoding arg158. Subsequently, digestion of polymerase chain reaction-amplified portions of exon 4 of the apo E gene with endonucleases HaeIII, TaqI, and Sau3AI demonstrated a second DNA variant that encoded a single amino acid substitution (gly127-->asp, G127D) due to a guanosine-to-adenosine nucleotide change resulting in the apo E1 isoform (G127D, R158C), which had arisen from a parent apo E2 allele. This mutation was confirmed with direct DNA sequencing. Incubation of very low density lipoprotein (VLDL) isolated from hyperlipidemic apo E1 subjects with J774 macrophages resulted in a 7- to 12-fold increase in cellular cholesterol ester compared with VLDL from apo E2/2 subjects. Although heterozygosity for apo E1 alone did not impair the interaction of VLDL with cellular receptors in vitro, its presence in subjects with type III HLP suggests that apo E1, perhaps in combination with secondary factors, may be causative for the dyslipidemia. PMID:7883834

  20. Apolipoprotein E polymorphism and outcome after mild to moderate traumatic brain injury: A study of patient population in India

    Directory of Open Access Journals (Sweden)

    Pruthi Nupur

    2010-01-01

    Full Text Available Background: The nature and extent of recovery after traumatic brain injury (TBI is heterogeneous. Apolipoprotein E (APOE plays a major role in repair of cell membrane and growth of neurites following injury to cells. Studies done on the western population have shown that the APOE e4 genotype is associated with poor survival following neurotrauma. Aim: To explore the association of APOE polymorphism and outcome following TBI in a patient population from a tertiary care hospital exclusive for neurological diseases in south India. Patients and Methods: Ninety eight patients who sustained mild to moderate TBI (computed tomography (CT scan brain showing traumatic parenchymal contusions were the subjects of the study and the study period was from November 2003 to December 2008. APOE polymorphism status was determined by PCR technique using venous blood. Patients were assessed on follow-up with a battery of four neuropsychological tests as well as Glasgow outcome scale. Results: Of the 98 patients, 20 (20% patients had at least one APOE e4 allele. A follow-up of minimum six months was available for 73 patients. None of the12 patients who had at least one APOE e4 allele had a poor outcome at six-month follow-up whereas 11(18% patients without an APOE e4 allele had a poor outcome (Fisher′s Exact test, P=0.192. On the neuropsychological tests, performance of patients with APOE e4 allele did not differ significantly from those without these alleles. Conclusion: This study does not support the current contention that the presence of APOE e4 allele should have a significant negative effect on the outcome after TBI.

  1. Nuclear microprobe investigation into the trace elemental contents of carotid artery walls of apolipoprotein E deficient mice

    International Nuclear Information System (INIS)

    Atherosclerosis is a progressive disease that causes lesions in large and medium-sized arteries. There is increasing evidence that the function of vascular endothelial cells is impaired by oxidation reactions, and that metal ions may participate in these processes. The nuclear microscopy facility in NUS, which has the ability to focus a 2 MeV proton beam down to sub micron spot sizes, was used to investigate the trace elemental changes (e.g. Zn and Fe) in atherosclerotic lesions in the common carotid artery of apolipoprotein E deficient mice fed a high fat diet. In this preliminary study, which is part of a larger study to investigate the effects of probucol on carotid artery atherosclerosis, two sets of mice were used; a test set fed a high fat diet +1% probucol, and a control set which was fed a high fat diet only. The results show that the Zn/Fe ratio was significantly higher in the media of arteries of probucol treated animals without overlying lesion (4.3) compared to the media with overlying lesion (1.3) (p = 0.004) for test mice. For the control mice, the arterial Zn/Fe ratio was 1.8 for media without overlying lesion, compared with 1.0 for media with overlying lesion (p = 0.1). Thus, for media without overlying lesion, the Zn/Fe ratio was significantly higher (p = 0.009) in probucol-treated (4.3) than control mice (1.8), whereas there was little difference in the ratios between the two groups in media with overlying lesion (1.3 compared with 1.0). These preliminary results are consistent with the idea that the levels of iron and zinc concentrations within the artery wall may influence the formation of atherosclerotic plaque in the carotid artery

  2. Influence of environmental enrichment and depleted uranium on behaviour, cholesterol and acetylcholine in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Lestaevel, P; Airault, F; Racine, R; Bensoussan, H; Dhieux, B; Delissen, O; Manens, L; Aigueperse, J; Voisin, P; Souidi, M

    2014-07-01

    Alzheimer's disease is associated with genetic risk factors, of which the apolipoprotein E (ApoE) is the most prevalent, and is affected by environmental factors that include education early in life and exposure to metals. The industrial and military use of depleted uranium (DU) resulted in an increase of its deposition in some areas and led to a possible environmental factor. The present study aims to ascertain the effects on the behaviour and the metabolism of cholesterol and acetylcholine of ApoE-/- mice exposed to enriched environment (EE) and exposed to DU (20 mg/L) for 14 weeks. Here we show that ApoE-/- mice were unaffected by the EE and their learning and memory were similar to those of the non-enriched ApoE-/- mice. ApoE-/- mice showed a significant decrease in total (-16 %) and free (-16 %) cholesterol in the entorhinal cortex in comparison to control wild-type mice. Whatever the housing conditions, the exposure to DU of ApoE-/- mice impaired working memory, but had no effect on anxiety-like behaviour, in comparison to control ApoE-/- mice. The exposure of ApoE-/- mice to DU also induced a trend toward higher total cholesterol content in the cerebral cortex (+15 %) compared to control ApoE-/- mice. In conclusion, these results demonstrate that enriched environment does not ameliorate neurobehaviour in ApoE-/- mice and that ApoE mutation induced specific effects on the brain cholesterol. These findings also suggested that DU exposure could modify the pathology in this ApoE model, with no influence of housing conditions. PMID:23749703

  3. Vitamin D deficiency and exogenous vitamin D excess similarly increase diffuse atherosclerotic calcification in apolipoprotein E knockout mice.

    Directory of Open Access Journals (Sweden)

    Timothy Ellam

    Full Text Available BACKGROUND: Observational data associate lower levels of serum vitamin D with coronary artery calcification, cardiovascular events and mortality. However, there is little interventional evidence demonstrating that moderate vitamin D deficiency plays a causative role in cardiovascular disease. This study examined the cardiovascular effects of dietary vitamin D deficiency and of vitamin D receptor agonist (paricalcitol administration in apolipoprotein E knockout mice. METHODS: Mice were fed atherogenic diets with normal vitamin D content (1.5 IU/kg or without vitamin D. Paricalcitol, or matched vehicle, was administered 3× weekly by intraperitoneal injection. Following 20 weeks of these interventions cardiovascular phenotype was characterized by histological assessment of aortic sinus atheroma, soluble markers, blood pressure and echocardiography. To place the cardiovascular assessments in the context of intervention effects on bone, structural changes at the tibia were assessed by microtomography. RESULTS: Vitamin D deficient diet induced significant reductions in plasma vitamin D (p<0.001, trabecular bone volume (p<0.01 and bone mineral density (p<0.005. These changes were accompanied by an increase in calcification density (number of calcifications per mm(2 of von Kossa-stained aortic sinus atheroma (461 versus 200, p<0.01. Paricalcitol administration suppressed parathyroid hormone (p<0.001, elevated plasma calcium phosphate product (p<0.005 and induced an increase in calcification density (472 versus 200, p<0.005 similar to that seen with vitamin D deficiency. Atheroma burden, blood pressure, metabolic profile and measures of left ventricular hypertrophy were unaffected by the interventions. CONCLUSION: Vitamin D deficiency, as well as excess, increases atherosclerotic calcification. This phenotype is induced before other measures of cardiovascular pathology associated clinically with vitamin D deficiency. Thus, maintenance of an optimal

  4. Analysis of the Association Between Apolipoprotein E Polymorphism and Cardiovascular Risk Factors in an Elderly Population with Longevity

    Directory of Open Access Journals (Sweden)

    Schwanke Carla Helena Augustin

    2002-01-01

    Full Text Available OBJECTIVE: To establish the allelic and genotypic frequencies related to apolipoprotein E (ApoE polymorphism and association of the genotypes with risk factors and cardiovascular morbidity in an elderly population with longevity. METHODS: We analyzed 70 elderly patients aged 80 years or more who were part of the Projeto Veranópolis. We used the gene amplification technique through the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and cleavage with the restriction enzyme Hha I to identify the ApoE genotypes. The most frequent genotypes were compared considering biological variables and cardiovascular risks and morbidity. RESULTS: The frequencies of the E2, E3, and E4 alleles were 0.05, 0.84, and 0.11, respectively, and of the genotypes were as follows: E3E3 (0.70, E3E4 (0.22, E2E3 (0.06, and E2E2 (0.02. Individuals with the E3E4 had a mean age greater than those with the E3E3. No association was observed between the genotypes and the variables analyzed, except for obesity, which was associated with the E3E3 genotype. Individuals with the E3E4 genotype had high levels of LDL-cholesterol and fibrinogen as compared with those with the E3E3 genotype. CONCLUSION: The results suggest that the E4E4 genotype may be associated with early mortality. A balance between the protective or neutral factors and the cardiovascular risk factors may occur among the individuals with different genotypes, attenuating the negative effects of the E4 allele.

  5. Metformin reduces the endotoxin-induced down-regulation of apolipoprotein E gene expression in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Stavri, Simona; Trusca, Violeta G.; Simionescu, Maya; Gafencu, Anca V., E-mail: anca.gafencu@icbp.ro

    2015-05-29

    The atheroprotective role of macrophage-derived apolipoprotein E (apoE) is well known. Our previous reports demonstrated that inflammatory stress down-regulates apoE expression in macrophages, aggravating atherogenesis. Metformin, extensively used as an anti-diabetic drug, has also anti-inflammatory properties, and thus confers vascular protection. In this study, we questioned whether metformin could have an effect on apoE expression in macrophages in normal conditions or under lipopolysaccharide (LPS)-induced stress. The results showed that metformin slightly increases the apoE expression only at high doses (5–10 mM). Low doses of metformin (1–3 mM) significantly reduce the LPS down-regulatory effect on apoE expression in macrophages. Our experiments demonstrated that LPS-induced NF-κB binds to the macrophage-specific distal regulatory element of apoE gene, namely to the multienhancer 2 (ME.2) and its 5′-deletion fragments. The NF-κB binding on ME.2 and apoE promoter has a down-regulatory effect. In addition, data revealed that metformin impairs NF-κB nuclear translocation, and thus, improves the apoE levels in macrophages under inflammatory stress. The positive effect of metformin in the inflammatory states, its clinical safety and low cost, make this drug a potential adjuvant in the therapeutic strategies for atherosclerosis. - Highlights: • High doses of metformin slightly increase apoE expression in macrophages. • Low doses of metformin up-regulate apoE gene in endotoxin-stressed macrophages. • Metformin reduces the negative effect of LPS on apoE expression by NF-κB inhibition.

  6. Estrogen stimulates expression of chicken hepatic vitellogenin II and very low-density apolipoprotein II through ER-α.

    Science.gov (United States)

    Li, Jun; Leghari, Imdad H; He, Bin; Zeng, Weidong; Mi, Yuling; Zhang, Caiqiao

    2014-08-01

    Steroid hormones and their receptors play pivotal roles throughout vertebrate reproduction and development. Egg formation in avian species is a prime example. The synthesis of egg yolk proteins by the liver is highly dependent on estrogen. Two major components of the yolk protein precursors, vitellogenin II (VTG II) and very low-density apolipoprotein II (ApoVLDL II), are synthesized in the liver of hens under estrogen stimulation and are subsequently transferred via the blood to the developing oocytes. Estrogen-inducible transcription can be mediated through estrogen receptors (ERs) (ER-α and ER-β) or through G protein-coupled receptor 30 (GPR30), but the exact participation of the individual receptor is not clear. Here, we determine the relative contribution of each transduction pathway in the synthesis of VTG II and ApoVLDL II in the hepatocytes by using selective compounds that are known to specifically interact with each of the ERs and GPR30. 17β-Estradiol and propyl pyrazole triol (PPT, ER-α agonist) induced increase in VTG II and ApoVLDL II mRNA expressions in a dose-dependent manner. A high concentration of diarylpropionitrile (DPN, which preferentially motivates ER-β) slightly stimulated the expression of VTG II and ApoVLDL II mRNAs. However, G-1 (a GPR30 agonist) failed to display any stimulating role. Methyl-piperidino-pyrazole (a highly selective ER-α antagonist) fully blocked the expression of both yolk precursors, which were upregulated by 17β-estradiol, PPT, and DPN. Considering that DPN can also provoke the action of ER-α at high concentration, this excludes the participation of ER-β and supports the role of ER-α. The aforementioned results indicate that estrogen stimulates the expression of VTG II and ApoVLDL II mRNAs predominantly through ER-α in the chicken liver. PMID:24938798

  7. Expression of endogenous and transfected apolipoprotein II and vitellogenin II genes in an estrogen responsive chicken liver cell line.

    Science.gov (United States)

    Binder, R; MacDonald, C C; Burch, J B; Lazier, C B; Williams, D L

    1990-02-01

    A recently described chicken liver cell line, LMH, was characterized to evaluate responsiveness to estrogen. Expression of the endogenous apolipoprotein (apo) II gene was induced by 17 beta-estradiol when LMH cells were cultured with chicken serum. The response was low and yielded apoll mRNA at only 0.3% of the level seen in estrogenized rooster liver. Higher levels of apoll mRNA were achieved when LMH cells were transiently transfected with an expression plasmid for estrogen receptor. A transfected apoll gene was strongly expressed only when cotransfected with receptor. Expression of the endogenous vitellogenin (VTG) II gene was not detected. However, when cotransfected with a receptor expression plasmid, VTG II reporter plasmids were expressed in LMH cells in response to 17 beta-estradiol. These results suggest that estrogen responsiveness of LMH cells is limited by the availability of functional receptor. Low levels of estrogen receptor mRNA were detected in LMH cells, and receptor binding sites and mRNA were greatly increased following transient transfection with a receptor expression plasmid. Using this transient transfection protocol, several VTG II reporter plasmids were compared in LMH cells and chick embryo fibroblasts. A plasmid containing VTG II estrogen response elements linked to a heterologous promoter was regulated by estrogen in both cell types. In contrast, reporter plasmids containing the VTG II promoter were regulated by estrogen in LMH cells but were not expressed at all in chick embryo fibroblasts. These results suggest that regulation of the VTG II gene involves cell type-specific elements in addition to estrogen response elements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2330000

  8. A case–control study on the effect of Apolipoprotein E genotypes on gastric cancer risk and progression

    International Nuclear Information System (INIS)

    Apolipoprotein E (ApoE) is a multifunctional protein playing both a key role in the metabolism of cholesterol and triglycerides, and in tissue repair and inflammation. The ApoE gene (19q13.2) has three major isoforms encoded by ε2, ε3 and ε4 alleles with the ε4 allele associated with hypercholesterolemia and the ε2 allele with the opposite effect. An inverse relationship between cholesterol levels and gastric cancer (GC) has been previously reported, although the relationship between apoE genotypes and GC has not been explored so far. One hundred and fifty-six gastric cancer cases and 444 hospital controls were genotyped for apoE polymorphism (ε2, ε3, ε4 alleles). The relationship between GC and putative risk factors was measured using the adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) from logistic regression analysis. A gene-environment interaction analysis was performed. The effect of the apoE genotypes on survival from GC was explored by a Kaplan–Meier analysis and Cox proportional hazard regression model. Subjects carrying at least one apoE ε2 allele have a significant 60% decrease of GC risk (OR=0.40, 95% CI: 0.19 – 0.84) compared with ε3 homozygotes. No significant interaction emerged between the ε4 or ε2 allele and environmental exposures, nor ε2 or ε4 alleles affected the median survival times, even after correcting for age, gender and stadium. Our study reports for the first time a protective effect of the ε2 allele against GC, that might be partly attributed to the higher antioxidant properties of ε2 compared with the ε3 or ε4 alleles. Given the study’s sample size, further studies are required to confirm our findings

  9. Apolipoprotein AV Accelerates Plasma Hydrolysis OfTriglyceride-Rich Lipoproteins By Interaction With Proteoglycan BoundLipoprotein Lipase

    Energy Technology Data Exchange (ETDEWEB)

    Merkel, Martin; Loeffler, Britta; Kluger, Malte; Fabig, Nathalie; Geppert, Gesa; Pennacchio, Len A.; Laatsch, Alexander; Heeren, Joerg

    2005-02-22

    Apolipoprotein A5 (APOA5) is associated with differences intriglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasmatriglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In hAPOA5 transgenic mice(hAPOA5tr), catabolism of chylomicrons and VLDL was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL).Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by crossbreeding a human LPL transgene with the apoa5 knockout, and the hAPOA5tr to an LPL deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5 deficient mice,however, over expression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr HDL, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line.A direct interaction between LPL and apoAV was found by ligand blotting.It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycans bound LPL for lipolysis.

  10. Differential susceptibity of transgenic mice lacking one or both apolipoprotein alleles to folate and vitamin E deprivation.

    Science.gov (United States)

    Shea, Thomas B; Ortiz, Daniela; Rogers, Eugene

    2004-06-01

    The E4 allele of apolipoprotein E (ApoE) is associated with neurodegeneration in part due to increased oxidative stress. Transgenic mice lacking ApoE (-/-) represent a model for the consequences of deficiencies in ApoE function. Dietary deficiency in folate and vitamin E has previously been shown to potentiate the impact of ApoE deficiency; ApoE-/- mice deprived of folate and vitamin E for 1 month demonstrated increased oxidative damage in brain tissue and impaired cognitive performance as compared to ApoE+/+ mice. Since individuals homozygous for E4 can demonstrate more increased risk for neurodegeneration and an earlier age of onset than individuals heterozygous for E4, we tested the impact of folate and vitamin E deprivation on ApoE+/- mice. Thiobarbituric acid-reactive substances in brain tissue of ApoE+/- were significantly increased compared to ApoE+/+ mice, but this increase was less than that observed in ApoE-/- mice. By contrast, livers of ApoE+/- and -/- mice displayed an identical increase over that of +/+ mice. ApoE-/- mice, but not +/- or +/+ mice, exhibited impaired cognitive performance in maze trials when deprived of folate and vitamin E. These findings support the notion that homozygous deficiency of ApoE function can be more severe than heterozygous deficiency. They further suggest that the impact of partial deficiency in ApoE function may present a latent risk that may manifest only when compounded by other factors such as dietary deficiency. PMID:15201481

  11. Apolipoprotein J/Clusterin is a novel structural component of human erythrocytes and a biomarker of cellular stress and senescence.

    Directory of Open Access Journals (Sweden)

    Marianna H Antonelou

    Full Text Available BACKGROUND: Secretory Apolipoprotein J/Clusterin (sCLU is a ubiquitously expressed chaperone that has been functionally implicated in several pathological conditions of increased oxidative injury, including aging. Nevertheless, the biological role of sCLU in red blood cells (RBCs remained largely unknown. In the current study we identified sCLU as a component of human RBCs and we undertook a detailed analysis of its cellular topology. Moreover, we studied the erythrocytic membrane sCLU content during organismal aging, in conditions of increased organismal stress and accelerated RBCs senescence, as well as during physiological in vivo cellular senescence. METHODOLOGY/PRINCIPAL FINDINGS: By using a combination of molecular, biochemical and high resolution microscopical methods we found that sCLU is a novel structural component of RBCs extra- and intracellular plasma membrane and cytosol. We observed that the RBCs membrane-associated sCLU decreases during organismal aging or exposure to acute stress (e.g. smoking, in patients with congenital hemolytic anemia, as well as during RBCs in vivo senescence. In all cases, sCLU reduction paralleled the expression of typical cellular senescence, redox imbalance and erythrophagocytosis markers which are also indicative of the senescence- and oxidative stress-mediated RBCs membrane vesiculation. CONCLUSIONS/SIGNIFICANCE: We propose that sCLU at the mature RBCs is not a silent remnant of the erythroid precursors, but an active component being functionally implicated in the signalling mechanisms of cellular senescence and oxidative stress-responses in both healthy and diseased organism. The reduced sCLU protein levels in the RBCs membrane following cell exposure to various endogenous or exogenous stressors closely correlates to the levels of cellular senescence and redox imbalance markers, suggesting the usefulness of sCLU as a sensitive biomarker of senescence and cellular stress.

  12. Microsomal triacylglycerol transfer protein prevents presecretory degradation of apolipoprotein B-100. A dithiothreitol-sensitive protease is involved.

    Science.gov (United States)

    Benoist, F; Nicodeme, E; Grand-Perret, T

    1996-09-15

    The role of microsomal triacylglycerol transfer protein (MTP) in the secretion of apolipoprotein B-100 (apoB-100) has been studied using an inhibitor of MTP: 4'-bromo-3'-methylmetaqualone. In vitro, this compound inhibits trioleoylglycerol transfer between lipid vesicles mediated by MTP with an IC50 of 0.9 microM whereas it does not inhibit the lipid transfer mediated by the cholesteryl ester transfer protein. In HepG2 cells, 4'-bromo-3'-methylmetaqualone inhibits the secretion of apoB-100 with an IC50 of 0.3 microM, without affecting the secretion of several other proteins like apoA-I or albumin. Moreover, there is no accumulation of apoB-100 in treated cells. Oleic acid, which increases apoB-100 secretion, only slightly modifies the IC50 of 4'-bromo-3'-methylmetaqualone (0.5 microM). The latter has no effect on the synthesis of major lipids within the cell, but decreases the secretion of triacylglycerol into apoB-100-containing lipoproteins. Pulse/chase experiments reveal that 4'-bromo-3'-methylmetaqualone acts on apoB-100 production either at the co-translational or post-translational level. The cysteine protease inhibitor N-acetyl-leucyl-leucyl-norleucinal does not protect apoB-100 from the 4'-bromo-3'-methylmetaqualone effect but seems to be involved in a later step of apoB-100 intracellular degradation. By contrast, dithiothreitol can totally reverse the effect of the MTP inhibitor on apoB-100 production. The mechanism of MTP-mediated lipid assembly with apoB-100 is discussed. PMID:8856075

  13. Utilization of cognitive support in episodic free recall as a function of apolipoprotein E and vitamin B12 or folate among adults aged 75 years and older

    OpenAIRE

    Bunce, D; Kivipelto, M.; Wahlin, A

    2004-01-01

    Apolipoprotein E (APOE), vitamin B12, and folate were examined in relation to free recall among 167 community-based older adults. Cognitive support at encoding and retrieval was also taken into account. Participants were classified as APOE e4 or non-e4 allele carriers and as either low or normal vitamin B12 or folate status. A significant association was identified between low vitamin B12 and the e4 genotype in respect to free recall, but only in circumstances of low cognitive support. This r...

  14. Enriched environment reduces apolipoprotein E (ApoE) in reactive astrocytes and attenuates inflammation of the peri-infarct tissue after experimental stroke

    DEFF Research Database (Denmark)

    Ruscher, Karsten; Johannesson, Emelie; Brugiere, Elena;

    2009-01-01

    Apolipoprotein E (ApoE), a cholesterol transporter and an immunomodulator, is brain protective after experimental stroke and implicated in brain repair. Here, we study the involvement of ApoE in the restoration of brain function after experimental stroke, by using animal housing conditions that...... differentially improve recovery after occlusion of the middle cerebral artery occlusion (MCAO). We found that after MCAO the ApoE levels increased in the injured hemisphere over a 30 days recovery period. The exception was a proximal narrow peri-infarct rim, in which ApoE was solely localized in S100beta...

  15. Apolipoprotein A-I possesses an anti-obesity effect associated with increase of energy expenditure and up-regulation of UCP1 in brown fat

    OpenAIRE

    Ruan, Xiangbo; Li, Zhenghu; Zhang, Yixuan; Yang, Ling; Pan, Yi; Wang, Zhenzhen; Feng, Gen-Sheng; Chen, Yan

    2010-01-01

    Abstract Apolipoprotein A-I (ApoA-I) is the most abundant protein constituent of high-density lipoprotein (HDL). Reduced plasma HDL and ApoA-I levels have been found to be associated with obesity and metabolic syndrome in human beings. However, whether or not ApoA-I has a direct effect on obesity is largely unknown. Here we analysed the anti-obesity effect of ApoA-I using two mouse models, a transgenic mouse with overexpression of ApoA-I and the mice administered with an ApoA-I mimetic peptid...

  16. C-->U editing of apolipoprotein B mRNA in marsupials: identification and characterisation of APOBEC-1 from the American opossum Monodelphus domestica.

    OpenAIRE

    Fujino, T; Navaratnam, N; Jarmuz, A; von Haeseler, A; Scott, J

    1999-01-01

    The C->U editing of RNA is widely found in plant and animal species. In mammals it is a discrete process confined to the editing of apolipoprotein B (apoB) mRNA in eutherians and the editing of the mitochondrial tRNA for glycine in marsupials. Here we have identified and characterised apoB mRNA editing in the American opossum Monodelphus domestica. The apoB mRNA editing site is highly conserved in the opossum and undergoes complete editing in the small intestine, but not in the liver or other...

  17. Apolipoprotein(a) inhibits in vitro tube formation in endothelial cells: identification of roles for Kringle V and the plasminogen activation system.

    Science.gov (United States)

    Liu, Lei; Boffa, Michael B; Koschinsky, Marlys L

    2013-01-01

    Elevated plasma concentrations of lipoprotein(a) are associated with increased risk for atherothrombotic diseases. Apolipoprotein(a), the unique glycoprotein component of lipoprotein(a), is characterized by the presence of multiple kringle domains, and shares a high degree of sequence homology with the serine protease zymogen plasminogen. It has been shown that angiostatin, a proteolytic fragment of plasminogen containing kringles 1-4, can effectively inhibit angiogenesis. Moreover, proteolytic fragments of plasminogen containing kringle 5 are even more potent inhibitors of angiogenesis than angiostatin. Despite its strong similarity with plasminogen, the role of apolipoprotein(a) in angiogenesis remains controversial, with both pro- and anti-angiogenic effects reported. In the current study, we evaluated the ability of apolipoprotein(a) to inhibit VEGF- and angiopoietin-induced tube formation in human umbilical cord endothelial cells. A 17 kringle-containing form of recombinant apo(a) (17K), corresponding to a well-characterized, physiologically-relevant form of the molecule, effectively inhibited tube formation induced by either VEGF or angiopoietin-1. Using additional recombinant apolipoprotein(a) (r-apo(a)) variants, we demonstrated that this effect was dependent on the presence of an intact lysine-binding site in kringle V domain of apo(a), but not on the presence of the functional lysine-binding site in apo(a) kringle IV type 10; sequences within in the amino-terminal half of the molecule were also not required for the inhibitory effects of apo(a). We also showed that the apo(a)-mediated inhibition tube formation could be reversed, in part by the addition of plasmin or urokinase plasminogen activator, or by removal of plasminogen from the system. Further, we demonstrated that apo(a) treated with glycosidases to remove sialic acid was significantly less effective in inhibiting tube formation. This is the first report of a functional role for the glycosylation

  18. Apolipoprotein(a inhibits in vitro tube formation in endothelial cells: identification of roles for Kringle V and the plasminogen activation system.

    Directory of Open Access Journals (Sweden)

    Lei Liu

    Full Text Available Elevated plasma concentrations of lipoprotein(a are associated with increased risk for atherothrombotic diseases. Apolipoprotein(a, the unique glycoprotein component of lipoprotein(a, is characterized by the presence of multiple kringle domains, and shares a high degree of sequence homology with the serine protease zymogen plasminogen. It has been shown that angiostatin, a proteolytic fragment of plasminogen containing kringles 1-4, can effectively inhibit angiogenesis. Moreover, proteolytic fragments of plasminogen containing kringle 5 are even more potent inhibitors of angiogenesis than angiostatin. Despite its strong similarity with plasminogen, the role of apolipoprotein(a in angiogenesis remains controversial, with both pro- and anti-angiogenic effects reported. In the current study, we evaluated the ability of apolipoprotein(a to inhibit VEGF- and angiopoietin-induced tube formation in human umbilical cord endothelial cells. A 17 kringle-containing form of recombinant apo(a (17K, corresponding to a well-characterized, physiologically-relevant form of the molecule, effectively inhibited tube formation induced by either VEGF or angiopoietin-1. Using additional recombinant apolipoprotein(a (r-apo(a variants, we demonstrated that this effect was dependent on the presence of an intact lysine-binding site in kringle V domain of apo(a, but not on the presence of the functional lysine-binding site in apo(a kringle IV type 10; sequences within in the amino-terminal half of the molecule were also not required for the inhibitory effects of apo(a. We also showed that the apo(a-mediated inhibition tube formation could be reversed, in part by the addition of plasmin or urokinase plasminogen activator, or by removal of plasminogen from the system. Further, we demonstrated that apo(a treated with glycosidases to remove sialic acid was significantly less effective in inhibiting tube formation. This is the first report of a functional role for the

  19. An Apolipoprotein A-I Mimetic Peptide Designed with a Reductionist Approach Stimulates Reverse Cholesterol Transport and Reduces Atherosclerosis in Mice

    OpenAIRE

    Ditiatkovski, Michael; D’Souza, Wilissa; Kesani, Rajitha; Chin-Dusting, Jaye; de Haan, Judy B; Remaley, Alan; Sviridov, Dmitri

    2013-01-01

    Apolipoprotein A-I (apoA-I) mimetic peptides are considered a promising novel therapeutic approach to prevent and/or treat atherosclerosis. An apoA-I mimetic peptide ELK-2A2K2E was designed with a reductionist approach and has shown exceptional activity in supporting cholesterol efflux but modest anti-inflammatory and anti-oxidant properties in vitro. In this study we compared these in vitro properties with the capacity of this peptide to modify rates of reverse cholesterol transport and deve...

  20. Folded Functional Lipid-Poor Apolipoprotein A-I Obtained by Heating of High-Density Lipoproteins: Relevance to HDL Biogenesis

    OpenAIRE

    Jayaraman, Shobini; Cavigiolio, Giorgio; Gursky, Olga

    2012-01-01

    High-density lipoproteins (HDL) remove cell cholesterol and protect from atherosclerosis. The major HDL protein is apolipoprotein A-I (apoA-I). Most plasma apoA-I circulates in lipoproteins, yet ~5% forms monomeric lipid-poor/free species. This metabolically active species is a primary cholesterol acceptor and is central to HDL biogenesis. Structural properties of lipid-poor apoA-I are unclear due to difficulties in isolating this transient species. We used thermal denaturation of human HDL t...