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Sample records for lipid ii flippase

  1. Bacillus subtilis homologs of MviN (MurJ), the putative Escherichia coli lipid II flippase, are not essential for growth.

    Science.gov (United States)

    Fay, Allison; Dworkin, Jonathan

    2009-10-01

    Although peptidoglycan synthesis is one of the best-studied metabolic pathways in bacteria, the mechanism underlying the membrane translocation of lipid II, the undecaprenyl-disaccharide pentapeptide peptidoglycan precursor, remains mysterious. Recently, it was proposed that the essential Escherichia coli mviN gene encodes the lipid II flippase. Bacillus subtilis contains four proteins that are putatively homologous to MviN, including SpoVB, previously reported to be necessary for spore cortex peptidoglycan synthesis during sporulation. MviN complemented the sporulation defect of a DeltaspoVB mutation, and SpoVB and another of the B. subtilis homologs, YtgP, complemented the growth defect of an E. coli strain depleted for MviN. Thus, these B. subtilis proteins are likely to be MviN homologs. However, B. subtilis strains lacking these four proteins have no defects in growth, indicating that they likely do not serve as lipid II flippases in this organism.

  2. Assay of flippase activity in proteoliposomes using fluorescent lipid derivatives

    DEFF Research Database (Denmark)

    Marek, Magdalena; Günther-Pomorski, Thomas

    2016-01-01

    Specific membrane proteins, termed lipid flippases, play a central role in facilitating the movement of lipids across cellular membranes. In this protocol, we describe the reconstitution of ATP-driven lipid flippases in liposomes and the analysis of their in vitro flippase activity based on the use...... of fluorescent lipid derivatives. Working with purified and reconstituted systems provides a well-defined experimental setup and allows to directly characterize these membrane proteins at the molecular level....

  3. Application of image cytometry to characterize heterologous lipid flippases in yeast

    DEFF Research Database (Denmark)

    Jensen, Maria Stumph; Costa, Sara; Theorin, Lisa

    2016-01-01

    is typically monitored by flow cytometry, a costly and maintenance-intensive method. Here, we have optimized a protocol to use an automated image-based cell counter to accurately measure lipid uptake by heterologous lipid flippases expressed in yeast. The method was validated by comparison with the classical...... flow cytometric evaluation of lipid-labeled cells. In addition, we demonstrated that expression of fluorescently tagged flippase complexes can be directly co-related with fluorescent lipid uptake using the image-based cell counter system. The method extends the number of techniques available...

  4. Final Report for DE-FG02-04ER15626: P-type ATPases in Plants – Role of Lipid Flippases in Membrane Biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Harper, Jeffrey F. [Univ. of Nevada, Reno, NV (United States)

    2015-02-24

    The long-range goal of the research is to understand the structure and biological functions of different P-type ATPases (ion pumps) in plant cells, and to use that knowledge to enhance the production of bioenergy from plants, or plant-research inspired technologies. Ptype ATPases include ion pumps that specifically transport H+, Ca2+, Zn2+, Cu2+, K+, or Na+, as well as at least one unusual subfamily that appears to function as lipid flippases, flipping specific lipids from one side of a membrane bilayer to the other. As a group, P-type ATPases are thought to consume more than 1/3 of the cellular ATP in typical eukaryotic cells. Recent research in the Harper lab focused on understanding the biochemical and biological functions of P-type ATPases that flip lipids. These flippases belong to the P4 subfamily of P-type ATPases. The activity of lipid flippases is thought to induce membrane curvature and/or create an asymmetry in which certain lipid head groups are preferential exposed to one surface or the other. In Arabidopsis thaliana there are 12 members of this family referred to as Aminophospholipid ATPase (ALA) 1 to ALA12. Using genetic knockouts, the Harper lab has established that this unusual subfamily of P-type ATPases are critical for plants to cope with even modest changes in temperature (e.g., down to 15°C, or up to 30°C). In addition, members of one subclade are critical for cell expansion, and loss of function mutants result in severe dwarfism. Other members of this same sub-clade are critical for pollen tube growth, and loss of function mutants are sterile under conditions of hot days and cold nights. While the cellular processes that depend on lipid flippases are still unclear, the genetic analysis of loss of function mutants clearly show they are of fundamental importance to plant growth and response to the environment.

  5. Shedding light on the role of lipid flippases in the secretory pathway

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura

    A fundamental feature of eukaryotic cells is the presence of distinct organelles surrounded by lipid bilayers. Assembly and maintenance of the various organellar membranes requires translocation of lipids from one leaflet of the bilayer to the other. Specific membrane proteins, termed lipid flipp...

  6. A subset of annular lipids is linked to the flippase activity of an ABC transporter.

    Science.gov (United States)

    Bechara, Chérine; Nöll, Anne; Morgner, Nina; Degiacomi, Matteo T; Tampé, Robert; Robinson, Carol V

    2015-03-01

    Lipids are critical components of membranes that could affect the properties of membrane proteins, yet the precise compositions of lipids surrounding membrane-embedded protein complexes is often difficult to discern. Here we report that, for the heterodimeric ABC transporter TmrAB, the extent of delipidation can be controlled by timed exposure to detergent. We subsequently characterize the cohort of endogenous lipids that are extracted in contact with the membrane protein complex, and show that with prolonged delipidation the number of neutral lipids is reduced in favour of their negatively charged counterparts. We show that lipid A is retained by the transporter and that the extent of its binding decreases during the catalytic cycle, implying that lipid A release is linked to adenosine tri-phosphate hydrolysis. Together, these results enable us to propose that a subset of annular lipids is invariant in composition, with negatively charged lipids binding tightly to TmrAB, and imply a role for this exporter in glycolipid translocation.

  7. Inositol depletion restores vesicle transport in yeast phospholipid flippase mutants.

    Science.gov (United States)

    Yamagami, Kanako; Yamamoto, Takaharu; Sakai, Shota; Mioka, Tetsuo; Sano, Takamitsu; Igarashi, Yasuyuki; Tanaka, Kazuma

    2015-01-01

    In eukaryotic cells, type 4 P-type ATPases function as phospholipid flippases, which translocate phospholipids from the exoplasmic leaflet to the cytoplasmic leaflet of the lipid bilayer. Flippases function in the formation of transport vesicles, but the mechanism remains unknown. Here, we isolate an arrestin-related trafficking adaptor, ART5, as a multicopy suppressor of the growth and endocytic recycling defects of flippase mutants in budding yeast. Consistent with a previous report that Art5p downregulates the inositol transporter Itr1p by endocytosis, we found that flippase mutations were also suppressed by the disruption of ITR1, as well as by depletion of inositol from the culture medium. Interestingly, inositol depletion suppressed the defects in all five flippase mutants. Inositol depletion also partially restored the formation of secretory vesicles in a flippase mutant. Inositol depletion caused changes in lipid composition, including a decrease in phosphatidylinositol and an increase in phosphatidylserine. A reduction in phosphatidylinositol levels caused by partially depleting the phosphatidylinositol synthase Pis1p also suppressed a flippase mutation. These results suggest that inositol depletion changes the lipid composition of the endosomal/TGN membranes, which results in vesicle formation from these membranes in the absence of flippases.

  8. A high-yield co-expression system for the purification of an intact drs2p-cdc50p lipid flippase complex, critically dependent on and stabilized by phosphatidylinositol-4-phosphate

    DEFF Research Database (Denmark)

    Azouaoui, Hassina; Montigny, Cédric; Ash, Miriam-Rose

    2014-01-01

    P-type ATPases from the P4 subfamily (P4-ATPases) are energy-dependent transporters, which are thought to establish lipid asymmetry in eukaryotic cell membranes. Together with their Cdc50 accessory subunits, P4-ATPases couple ATP hydrolysis to lipid transport from the exoplasmic to the cytoplasmic...... leaflet of plasma membranes, late Golgi membranes, and endosomes. To gain insights into the structure and function of these important membrane pumps, robust protocols for expression and purification are required. In this report, we present a procedure for high-yield co-expression of a yeast flippase......, the Drs2p-Cdc50p complex. After recovery of yeast membranes expressing both proteins, efficient purification was achieved in a single step by affinity chromatography on streptavidin beads, yielding ∼1-2 mg purified Drs2p-Cdc50p complex per liter of culture. Importantly, the procedure enabled us to recover...

  9. The O-Antigen Flippase Wzk Can Substitute for MurJ in Peptidoglycan Synthesis in Helicobacter pylori and Escherichia coli

    Science.gov (United States)

    Elhenawy, Wael; Davis, Rebecca M.; Fero, Jutta; Salama, Nina R.; Felman, Mario F.

    2016-01-01

    The peptidoglycan (PG) cell wall is an essential component of the cell envelope of most bacteria. Biogenesis of PG involves a lipid-linked disaccharide-pentapeptide intermediate called lipid II, which must be translocated across the cytoplasmic membrane after it is synthesized in the inner leaflet of this bilayer. Accordingly, it has been demonstrated that MurJ, the proposed lipid II flippase in Escherichia coli, is required for PG biogenesis, and thereby viability. In contrast, MurJ is not essential in Bacillus subtilis because this bacterium produces AmJ, an unrelated protein that is functionally redundant with MurJ. In this study, we investigated why MurJ is not essential in the prominent gastric pathogen, Helicobacter pylori. We found that in this bacterium, Wzk, the ABC (ATP-binding cassette) transporter that flips the lipid-linked O- or Lewis- antigen precursors across the inner membrane, is redundant with MurJ for cell viability. Heterologous expression of wzk in E. coli also suppresses the lethality caused by the loss of murJ. Furthermore, we show that this cross-species complementation is abolished when Wzk is inactivated by mutations that target a domain predicted to be required for ATPase activity. Our results suggest that Wzk can flip lipid II, implying that Wzk is the flippase with the most relaxed specificity for lipid-linked saccharides ever identified. PMID:27537185

  10. A High-Yield Co-Expression System for the Purification of an Intact Drs2p-Cdc50p Lipid Flippase Complex, Critically Dependent on and Stabilized by Phosphatidylinositol-4-Phosphate

    Science.gov (United States)

    Azouaoui, Hassina; Montigny, Cédric; Ash, Miriam-Rose; Fijalkowski, Frank; Jacquot, Aurore; Grønberg, Christina; López-Marqués, Rosa L.; Palmgren, Michael G.; Garrigos, Manuel; le Maire, Marc; Decottignies, Paulette; Gourdon, Pontus; Nissen, Poul; Champeil, Philippe; Lenoir, Guillaume

    2014-01-01

    P-type ATPases from the P4 subfamily (P4-ATPases) are energy-dependent transporters, which are thought to establish lipid asymmetry in eukaryotic cell membranes. Together with their Cdc50 accessory subunits, P4-ATPases couple ATP hydrolysis to lipid transport from the exoplasmic to the cytoplasmic leaflet of plasma membranes, late Golgi membranes, and endosomes. To gain insights into the structure and function of these important membrane pumps, robust protocols for expression and purification are required. In this report, we present a procedure for high-yield co-expression of a yeast flippase, the Drs2p-Cdc50p complex. After recovery of yeast membranes expressing both proteins, efficient purification was achieved in a single step by affinity chromatography on streptavidin beads, yielding ∼1–2 mg purified Drs2p-Cdc50p complex per liter of culture. Importantly, the procedure enabled us to recover a fraction that mainly contained a 1∶1 complex, which was assessed by size-exclusion chromatography and mass spectrometry. The functional properties of the purified complex were examined, including the dependence of its catalytic cycle on specific lipids. The dephosphorylation rate was stimulated in the simultaneous presence of the transported substrate, phosphatidylserine (PS), and the regulatory lipid phosphatidylinositol-4-phosphate (PI4P), a phosphoinositide that plays critical roles in membrane trafficking events from the trans-Golgi network (TGN). Likewise, overall ATP hydrolysis by the complex was critically dependent on the simultaneous presence of PI4P and PS. We also identified a prominent role for PI4P in stabilization of the Drs2p-Cdc50p complex towards temperature- or C12E8-induced irreversible inactivation. These results indicate that the Drs2p-Cdc50p complex remains functional after affinity purification and that PI4P as a cofactor tightly controls its stability and catalytic activity. This work offers appealing perspectives for detailed structural and

  11. Protein kinase Gin4 negatively regulates flippase function and controls plasma membrane asymmetry.

    Science.gov (United States)

    Roelants, Françoise M; Su, Brooke M; von Wulffen, Joachim; Ramachandran, Subramaniam; Sartorel, Elodie; Trott, Amy E; Thorner, Jeremy

    2015-02-02

    Plasma membrane function requires distinct leaflet lipid compositions. Two of the P-type ATPases (flippases) in yeast, Dnf1 and Dnf2, translocate aminoglycerophospholipids from the outer to the inner leaflet, stimulated via phosphorylation by cortically localized protein kinase Fpk1. By monitoring Fpk1 activity in vivo, we found that Fpk1 was hyperactive in cells lacking Gin4, a protein kinase previously implicated in septin collar assembly. Gin4 colocalized with Fpk1 at the cortical site of future bud emergence and phosphorylated Fpk1 at multiple sites, which we mapped. As judged by biochemical and phenotypic criteria, a mutant (Fpk1(11A)), in which 11 sites were mutated to Ala, was hyperactive, causing increased inward transport of phosphatidylethanolamine. Thus, Gin4 is a negative regulator of Fpk1 and therefore an indirect negative regulator of flippase function. Moreover, we found that decreasing flippase function rescued the growth deficiency of four different cytokinesis mutants, which suggests that the primary function of Gin4 is highly localized control of membrane lipid asymmetry and is necessary for optimal cytokinesis. © 2015 Roelants et al.

  12. Dynamic Transbilayer Lipid Asymmetry

    OpenAIRE

    van Meer, Gerrit

    2011-01-01

    Flippases move lipids from the outer leaflet of the membrane to the inner leaflet; floppases export them in the opposite direction. This creates an asymmetry critical for membrane function and facilitates vesicle budding.

  13. Cfs1p, a Novel Membrane Protein in the PQ-Loop Family, Is Involved in Phospholipid Flippase Functions in Yeast

    Directory of Open Access Journals (Sweden)

    Takaharu Yamamoto

    2017-01-01

    Full Text Available Type 4 P-type ATPases (P4-ATPases function as phospholipid flippases, which translocate phospholipids from the exoplasmic leaflet to the cytoplasmic leaflet of the lipid bilayer, to generate and maintain asymmetric distribution of phospholipids at the plasma membrane and endosomal/Golgi membranes. The budding yeast Saccharomyces cerevisiae has four heteromeric flippases (Drs2p, Dnf1p, Dnf2p, and Dnf3p, associated with the Cdc50p family noncatalytic subunit, and one monomeric flippase, Neo1p. They have been suggested to function in vesicle formation in membrane trafficking pathways, but details of their mechanisms remain to be clarified. Here, to search for novel factors that functionally interact with flippases, we screened transposon insertional mutants for strains that suppressed the cold-sensitive growth defect in the cdc50Δ mutant. We identified a mutation of YMR010W encoding a novel conserved membrane protein that belongs to the PQ-loop family including the cystine transporter cystinosin and the SWEET sugar transporters. We named this gene CFS1 (cdc fifty suppressor 1. GFP-tagged Cfs1p was partially colocalized with Drs2p and Neo1p to endosomal/late Golgi membranes. Interestingly, the cfs1Δ mutation suppressed growth defects in all flippase mutants. Accordingly, defects in membrane trafficking in the flippase mutants were also suppressed. These results suggest that Cfs1p and flippases function antagonistically in membrane trafficking pathways. A growth assay to assess sensitivity to duramycin, a phosphatidylethanolamine (PE-binding peptide, suggested that the cfs1Δ mutation changed PE asymmetry in the plasma membrane. Cfs1p may thus be a novel regulator of phospholipid asymmetry.

  14. A high-yield co-expression system for the purification of an intact drs2p-cdc50p lipid flippase complex, critically dependent on and stabilized by phosphatidylinositol-4-phosphate

    DEFF Research Database (Denmark)

    Azouaoui, Hassina; Montigny, Cédric; Ash, Miriam-Rose;

    2014-01-01

    P-type ATPases from the P4 subfamily (P4-ATPases) are energy-dependent transporters, which are thought to establish lipid asymmetry in eukaryotic cell membranes. Together with their Cdc50 accessory subunits, P4-ATPases couple ATP hydrolysis to lipid transport from the exoplasmic to the cytoplasmic...... in the simultaneous presence of the transported substrate, phosphatidylserine (PS), and the regulatory lipid phosphatidylinositol-4-phosphate (PI4P), a phosphoinositide that plays critical roles in membrane trafficking events from the trans-Golgi network (TGN). Likewise, overall ATP hydrolysis by the complex...... was critically dependent on the simultaneous presence of PI4P and PS. We also identified a prominent role for PI4P in stabilization of the Drs2p-Cdc50p complex towards temperature- or C12E8-induced irreversible inactivation. These results indicate that the Drs2p-Cdc50p complex remains functional after affinity...

  15. On the molecular mechanism of flippase- and scramblase-mediated phospholipid transport.

    Science.gov (United States)

    Montigny, Cédric; Lyons, Joseph; Champeil, Philippe; Nissen, Poul; Lenoir, Guillaume

    2016-08-01

    Phospholipid flippases are key regulators of transbilayer lipid asymmetry in eukaryotic cell membranes, critical to many trafficking and signaling pathways. P4-ATPases, in particular, are responsible for the uphill transport of phospholipids from the exoplasmic to the cytosolic leaflet of the plasma membrane, as well as membranes of the late secretory/endocytic pathways, thereby establishing transbilayer asymmetry. Recent studies combining cell biology and biochemical approaches have improved our understanding of the path taken by lipids through P4-ATPases. Additionally, identification of several protein families catalyzing phospholipid 'scrambling', i.e. disruption of phospholipid asymmetry through energy-independent bi-directional phospholipid transport, as well as the recent report of the structure of such a scramblase, opens the way to a deeper characterization of their mechanism of action. Here, we discuss the molecular nature of the mechanism by which lipids may 'flip' across membranes, with an emphasis on active lipid transport catalyzed by P4-ATPases. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.

  16. Endometriosis and Type I Interferon & Characterization of a Mammalian Flippase

    DEFF Research Database (Denmark)

    Vestergaard, Anna Lindeløv

    2010-01-01

    , and ERa, when analyzed by bisulfate PCR and melting curve analysis. Also, no mutations of BRAF, HRAS, NRAS, CTNNB1, CDK4, FGFR3, PIK3CA, P53, and PTEN were detected by PCR denaturing gradient gel electrophoresis analysis. A well-known cancer-associated mutation in KRAS was detected in a single...... protein family are believed to be chaperones or additional subunits to these enzymes. The molecular mechanism of the flippases is currently unknown, and whereas studies of the yeast family members have provided some functional knowledge on the matter, the mammalian homologs are still fairly...

  17. Resistance of Gram-positive bacteria to nisin is not determined by Lipid II levels

    NARCIS (Netherlands)

    Kramer, NE; Smid, EJ; Kok, J; de Kruijff, B; Kuipers, OP; Breukink, E; Kramer, Naomi E.; Smid, Eddy J.

    2004-01-01

    Lipid II is essential for nisin-mediated pore formation at nano-molar concentrations. We tested whether nisin resistance could result from different Lipid II levels, by comparing the maximal Lipid II pool in Micrococcus flavus (sensitive) and Listeria monocytogenes (relatively insensitive) and their

  18. Mice deficient in the putative phospholipid flippase ATP11C exhibit altered erythrocyte shape, anemia, and reduced erythrocyte life span.

    Science.gov (United States)

    Yabas, Mehmet; Coupland, Lucy A; Cromer, Deborah; Winterberg, Markus; Teoh, Narci C; D'Rozario, James; Kirk, Kiaran; Bröer, Stefan; Parish, Christopher R; Enders, Anselm

    2014-07-11

    Transmembrane lipid transporters are believed to establish and maintain phospholipid asymmetry in biological membranes; however, little is known about the in vivo function of the specific transporters involved. Here, we report that developing erythrocytes from mice lacking the putative phosphatidylserine flippase ATP11C showed a lower rate of PS translocation in vitro compared with erythrocytes from wild-type littermates. Furthermore, the mutant mice had an elevated percentage of phosphatidylserine-exposing mature erythrocytes in the periphery. Although erythrocyte development in ATP11C-deficient mice was normal, the mature erythrocytes had an abnormal shape (stomatocytosis), and the life span of mature erythrocytes was shortened relative to that in control littermates, resulting in anemia in the mutant mice. Thus, our findings uncover an essential role for ATP11C in erythrocyte morphology and survival and provide a new candidate for the rare inherited blood disorder stomatocytosis with uncompensated anemia. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. In vivo cluster formation of nisin and lipid II is correlated with membrane depolarization.

    Science.gov (United States)

    Tol, Menno B; Morales Angeles, Danae; Scheffers, Dirk-Jan

    2015-01-01

    Nisin and related lantibiotics kill bacteria by pore formation or by sequestering lipid II. Some lantibiotics sequester lipid II into clusters, which were suggested to kill cells through delocalized peptidoglycan synthesis. Here, we show that cluster formation is always concomitant with (i) membrane pore formation and (ii) membrane depolarization. Nisin variants that cluster lipid II kill L-form bacteria with similar efficiency, suggesting that delocalization of peptidoglycan synthesis is not the primary killing mechanism of these lantibiotics.

  20. Flippase (FLP) recombinase-mediated marker recycling in the dermatophyte Arthroderma vanbreuseghemii.

    Science.gov (United States)

    Yamada, Yohko; Maeda, Mari; Alshahni, Mohamed Mahdi; Monod, Michel; Staib, Peter; Yamada, Tsuyoshi

    2014-10-01

    Biological processes can be elucidated by investigating complex networks of relevant factors and genes. However, this is not possible in species for which dominant selectable markers for genetic studies are unavailable. To overcome the limitation in selectable markers for the dermatophyte Arthroderma vanbreuseghemii (anamorph: Trichophyton mentagrophytes), we adapted the flippase (FLP) recombinase-recombination target (FRT) site-specific recombination system from the yeast Saccharomyces cerevisiae as a selectable marker recycling system for this fungus. Taking into account practical applicability, we designed FLP/FRT modules carrying two FRT sequences as well as the flp gene adapted to the pathogenic yeast Candida albicans (caflp) or a synthetic codon-optimized flp (avflp) gene with neomycin resistance (nptII) cassette for one-step marker excision. Both flp genes were under control of the Trichophyton rubrum copper-repressible promoter (PCTR4). Molecular analyses of resultant transformants showed that only the avflp-harbouring module was functional in A. vanbreuseghemii. Applying this system, we successfully produced the Ku80 recessive mutant strain devoid of any selectable markers. This strain was subsequently used as the recipient for sequential multiple disruptions of secreted metalloprotease (fungalysin) (MEP) or serine protease (SUB) genes, producing mutant strains with double MEP or triple SUB gene deletions. These results confirmed the feasibility of this system for broad-scale genetic manipulation of dermatophytes, advancing our understanding of functions and networks of individual genes in these fungi.

  1. An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II

    NARCIS (Netherlands)

    Hasper, Hester E.; Kramer, Naomi E.; Smith, James L.; Hillman, J. D.; Zachariah, Cherian; Kuipers, Oscar P.; de Kruijff, Ben; Breukink, Eefjan

    2006-01-01

    Lantibiotics are polycyclic peptides containing unusual amino acids, which have binding specificity for bacterial cells, targeting the bacterial cell wall component lipid II to form pores and thereby lyse the cells. Yet several members of these lipid II - targeted lantibiotics are too short to be ab

  2. In vivo cluster formation of nisin and Lipid II is correlated with membrane depolarization

    NARCIS (Netherlands)

    Tol, Menno B; Angeles, Danae Morales; Scheffers, Dirk-Jan

    2015-01-01

    Nisin and related lantibiotics kill bacteria by pore formation, or by sequestering Lipid II. Some lantibiotics sequester Lipid II into clusters, which were suggested to kill cells through delocalized peptidoglycan synthesis. Here, we show that cluster formation is always concomitant with (i)

  3. Plectasin, a Fungal Defensin, Targets the Bacterial Cell Wall Precursor Lipid II

    DEFF Research Database (Denmark)

    Schneider, Tanja; Kruse, Thomas; Wimmer, Reinhard

    2010-01-01

    that plectasin, a fungal defensin, acts by directly binding the bacterial cell-wall precursor Lipid II. A wide range of genetic and biochemical approaches identify cell-wall biosynthesis as the pathway targeted by plectasin. In vitro assays for cell-wall synthesis identified Lipid II as the specific cellular...

  4. Identification of FtsW as a transporter of lipid-linked cell wall precursors across the membrane

    Science.gov (United States)

    Mohammadi, Tamimount; van Dam, Vincent; Sijbrandi, Robert; Vernet, Thierry; Zapun, André; Bouhss, Ahmed; Diepeveen-de Bruin, Marlies; Nguyen-Distèche, Martine; de Kruijff, Ben; Breukink, Eefjan

    2011-01-01

    Bacterial cell growth necessitates synthesis of peptidoglycan. Assembly of this major constituent of the bacterial cell wall is a multistep process starting in the cytoplasm and ending in the exterior cell surface. The intracellular part of the pathway results in the production of the membrane-anchored cell wall precursor, Lipid II. After synthesis this lipid intermediate is translocated across the cell membrane. The translocation (flipping) step of Lipid II was demonstrated to require a specific protein (flippase). Here, we show that the integral membrane protein FtsW, an essential protein of the bacterial division machinery, is a transporter of the lipid-linked peptidoglycan precursors across the cytoplasmic membrane. Using Escherichia coli membrane vesicles we found that transport of Lipid II requires the presence of FtsW, and purified FtsW induced the transbilayer movement of Lipid II in model membranes. This study provides the first biochemical evidence for the involvement of an essential protein in the transport of lipid-linked cell wall precursors across biogenic membranes. PMID:21386816

  5. Wheat leaf lipids during heat stress: II. Lipids experiencing coordinated metabolism are detected by analysis of lipid co-occurrence.

    Science.gov (United States)

    Narayanan, Sruthi; Prasad, P V Vara; Welti, Ruth

    2016-03-01

    Identifying lipids that experience coordinated metabolism during heat stress would provide information regarding lipid dynamics under stress conditions and assist in developing heat-tolerant wheat varieties. We hypothesized that co-occurring lipids, which are up-regulated or down-regulated together through time during heat stress, represent groups that can be explained by coordinated metabolism. Wheat plants (Triticum aestivum L.) were subjected to 12 days of high day and/or night temperature stress, followed by a 4-day recovery period. Leaves were sampled at four time points, and 165 lipids were measured by electrospray ionization-tandem mass spectrometry. Correlation analysis of lipid levels in 160 leaf samples from each of two wheat genotypes revealed 13 groups of lipids. Lipids within each group co-occurred through the high day and night temperature stress treatments. The lipid groups can be broadly classified as groups containing extraplastidic phospholipids, plastidic glycerolipids, oxidized glycerolipids, triacylglycerols, acylated sterol glycosides and sterol glycosides. Current knowledge of lipid metabolism suggests that the lipids in each group co-occur because they are regulated by the same enzyme(s). The results suggest that increases in activities of desaturating, oxidizing, glycosylating and acylating enzymes lead to simultaneous changes in levels of multiple lipid species during high day and night temperature stress in wheat.

  6. Mice Deficient in the Putative Phospholipid Flippase ATP11C Exhibit Altered Erythrocyte Shape, Anemia, and Reduced Erythrocyte Life Span*♦

    Science.gov (United States)

    Yabas, Mehmet; Coupland, Lucy A.; Cromer, Deborah; Winterberg, Markus; Teoh, Narci C.; D'Rozario, James; Kirk, Kiaran; Bröer, Stefan; Parish, Christopher R.; Enders, Anselm

    2014-01-01

    Transmembrane lipid transporters are believed to establish and maintain phospholipid asymmetry in biological membranes; however, little is known about the in vivo function of the specific transporters involved. Here, we report that developing erythrocytes from mice lacking the putative phosphatidylserine flippase ATP11C showed a lower rate of PS translocation in vitro compared with erythrocytes from wild-type littermates. Furthermore, the mutant mice had an elevated percentage of phosphatidylserine-exposing mature erythrocytes in the periphery. Although erythrocyte development in ATP11C-deficient mice was normal, the mature erythrocytes had an abnormal shape (stomatocytosis), and the life span of mature erythrocytes was shortened relative to that in control littermates, resulting in anemia in the mutant mice. Thus, our findings uncover an essential role for ATP11C in erythrocyte morphology and survival and provide a new candidate for the rare inherited blood disorder stomatocytosis with uncompensated anemia. PMID:24898253

  7. Phospholipid flippase associates with cisplatin resistance in plasma membrane of lung adenocarcinoma A549 cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The fusion of the liposomes containing N-(7-nitro-2, 1, 3-benzoxadiazol-4-yl)-i ,2-hexadecanoylSn-glycero-3-1abeled phosphatidylethanolamine (NBD-PE) with A549 and A549/DDP cells was performed, and the activity of the phospholipid flippase in the plasma membrane of the cells was measured by fluorescence intensity change of NBDPE in the outer membrane. When A549 or A549/DDP cells containing N BD-PE were incubated at 37 C for 0, 30, 60 and 90 min, the fluorescence intensities in the outer membrane of the cells were 0%, 1.4%, 2.9% and 7.8% for A59cells, and 0%, 10.5 %, 15. 5 % and 18.3 % for A549/DDP cells respectively, demonstrating that the phospholipid flippase was distributed in the plasma membrane of As49 cells, but its activity in the drug-resistant A549/DDP cells was much higher than that in the A549 cells. When the A549/DDP cells were incubated with a multidrug resistance reverse agent, verapamil, for 60 min at 37C, the results showed that the NBD-PE in outer membrane decreased by 25.0% compared with the control's. Furthermore, when A549/DDP cells were incubated with 25 μmol/L cisplatin, which is a specific anticancer drug, the flippase activity decreased by 31.6%, and it further decreased with the increase of cisplatin concentration, suggesting that phospholipid flippase in the membrane might be related to the cisplatin-resistance of human lung adenocarcinoma cancer cells.

  8. Lipid-II Independent Antimicrobial Mechanism of Nisin Depends On Its Crowding And Degree Of Oligomerization

    Science.gov (United States)

    Prince, Ashutosh; Sandhu, Padmani; Kumar, Pankaj; Dash, Eva; Sharma, Shingarika; Arakha, Manoranjan; Jha, Suman; Akhter, Yusuf; Saleem, Mohammed

    2016-11-01

    Nisin inhibits bacterial growth by generating pores in cell membrane and interrupting cell-wall biosynthesis through specific lipid II interaction. However, the role of the hinge region and C-terminus residues of the peptide in antibacterial action of nisin is largely unknown. Here, using molecular dynamics simulations and experimental approach, we report that at high concentration regimes of nisin, interaction with phospholipids may equally deform the bacterial cell membranes even under significantly varying amounts of lipid-II. Membrane thinning, destabilization and decrease in lipid density depend on the degree of oligomerization of nisin. Growth kinetics of Bacillus subtilis and Escherichia coli interestingly show recovery by extended lag phase under low concentrations of nisin treatment while high concentrations of nisin caused decrease in cell viability as recorded by striking reduction in membrane potential and surface area. The significant changes in the dipole potential and fluorescence anisotropy were observed in negatively charged membranes in the absence of lipid-II with increasing concentration of nisin. The identical correlation of cell viability, membrane potential dissipation and morphology with the concentration regime of nisin, in both Bacillus subtilis (lipid II rich) and Escherichia coli (lipid II impoverished), hints at a non-specific physical mechanism where degree of membrane deformation depends on degree of crowding and oligomerization of nisin.

  9. Quality control of photosystem II: lipid peroxidation accelerates photoinhibition under excessive illumination.

    Directory of Open Access Journals (Sweden)

    Tiffanie Chan

    Full Text Available Environmental stresses lower the efficiency of photosynthesis and sometimes cause irreversible damage to plant functions. When spinach thylakoids and Photosystem II membranes were illuminated with excessive visible light (100-1,000 µmol photons m(-1 s(-1 for 10 min at either 20°C or 30°C, the optimum quantum yield of Photosystem II decreased as the light intensity and temperature increased. Reactive oxygen species and endogenous cationic radicals produced through a photochemical reaction at and/or near the reaction center have been implicated in the damage to the D1 protein. Here we present evidence that lipid peroxidation induced by the illumination is involved in the damage to the D1 protein and the subunits of the light-harvesting complex of Photosystem II. This is reasoned from the results that considerable lipid peroxidation occurred in the thylakoids in the light, and that lipoxygenase externally added in the dark induced inhibition of Photosystem II activity in the thylakoids, production of singlet oxygen, which was monitored by electron paramagnetic resonance spin trapping, and damage to the D1 protein, in parallel with lipid peroxidation. Modification of the subunits of the light-harvesting complex of Photosystem II by malondialdehyde as well as oxidation of the subunits was also observed. We suggest that mainly singlet oxygen formed through lipid peroxidation under light stress participates in damaging the Photosystem II subunits.

  10. Lipids in the Structure of Photosystem I, Photosystem II and the Cytochrome b6f Complex

    NARCIS (Netherlands)

    Kern, Jan; Zouni, Athina; Guskov, Albert; Krauss, Norbert; Wada, Hajime; Murata, Norio

    2009-01-01

    This chapter describes the data accumulated in the last decade regarding the specific function of lipids in oxygenic photosynthesis, based on crystal structures of at least 3.0 Å resolution of the main photosynthetic membrane protein—pigment complexes, photosystem I, photosystem II and cytochrome b6

  11. Lipids in the Structure of Photosystem I, Photosystem II and the Cytochrome b6f Complex

    NARCIS (Netherlands)

    Kern, Jan; Zouni, Athina; Guskov, Albert; Krauss, Norbert; Wada, Hajime; Murata, Norio

    2009-01-01

    This chapter describes the data accumulated in the last decade regarding the specific function of lipids in oxygenic photosynthesis, based on crystal structures of at least 3.0 Å resolution of the main photosynthetic membrane protein—pigment complexes, photosystem I, photosystem II and cytochrome

  12. Lipids as indicators of paleoclimatic changes, II: terrestrial biomarkers

    Directory of Open Access Journals (Sweden)

    Luiz A. S. Madureira

    1999-01-01

    Full Text Available Variations in the abundance of specific lipid biomarker compounds derived from terrestrial sources are shown to be closely related to past climatic changes. Despite biodegradation processes, which take place mostly at the water column and sediment water interface, these compounds are found well preserved in oceanic sediments. Here, their relative distribution is employed as a tool to assess changes in terrestrial fluxes to the seabed accompanying climatic variations during glacial and interglacial intervals. These changes in biomarker distribution were estimated in two sediment cores taken ttom the eastern North Atlantic, covering the past 210,000 years. Comparisons with other paleoclimate proxies showed good agreement and suggest that some specific groups of biomarkers are important indicators of changes in terrestrial inputs to the sea.A variação na abundância de alguns biomarcadores lipídicos derivados de aportes terrestres pode estar relacionada com mudanças climáticas no passado. Apesar dos processos de biodegradação que, na grande maioria, ocorrem na coluna aquática e na interface sedimento-água, esses compostos são encontrados bem preservados em sedimentos oceânicos. Nesse trabalho, a distribuição relativa desses compostos é empregada como uma ferramenta para avaliar mudanças no transporte de material terrestre para o mar em paralelo às variações climáticas durante os intervalos glaciais e interglaciais. As mudanças na distribuição dos biomarcadores foram estimadas em dois testemunhos coletados ao leste do Atlântico Norte e que correspondem aos últimos 210 mil anos. Os resultados mostraram uma boa correlação entre a distribuição dos biomarcadores e outros parâmetros paleoclimáticos previamente avaliados nos perfis, sugerindo que alguns grupos específicos de compostos orgânicos são importantes indicadores de aporte terrestre para ornar.

  13. Zn(II)-dipicolylamine-based metallo-lipids as novel non-viral gene vectors.

    Science.gov (United States)

    Su, Rong-Chuan; Liu, Qiang; Yi, Wen-Jing; Zhao, Zhi-Gang

    2017-08-01

    In this study, a series of Zn(II)-dipicolylamine (Zn-DPA) based cationic lipids bearing different hydrophobic tails (long chains, α-tocopherol, cholesterol or diosgenin) were synthesized. Structure-activity relationship (SAR) of these lipids was studied in detail by investigating the effects of several structural aspects including the type of hydrophobic tails, the chain length and saturation degree. In addition, several assays were used to study their interactions with plasmid DNA, and results reveal that these lipids could condense DNA into nanosized particles with appropriate size and zeta-potentials. MTT-based cell viability assays showed that lipoplexes 5 had low cytotoxicity. The in vitro gene transfection studies showed the hydrophobic tails clearly affected the TE, and hexadecanol-containing lipid 5b gives the best TE, which was 2.2 times higher than bPEI 25k in the presence of 10% serum. The results not only demonstrate that these lipids might be promising non-viral gene vectors, but also afford us clues for further optimization of lipidic gene delivery materials.

  14. Semisynthetic Lipopeptides Derived from Nisin Display Antibacterial Activity and Lipid II Binding on Par with That of the Parent Compound.

    Science.gov (United States)

    Koopmans, Timo; Wood, Thomas M; 't Hart, Peter; Kleijn, Laurens H J; Hendrickx, Antoni P A; Willems, Rob J L; Breukink, Eefjan; Martin, Nathaniel I

    2015-07-29

    The lipid II-binding N-terminus of nisin, comprising the so-called A/B ring system, was synthetically modified to provide antibacterially active and proteolytically stable derivatives. A variety of lipids were coupled to the C-terminus of the nisin A/B ring system to generate semisynthetic constructs that display potent inhibition of bacterial growth, with activities approaching that of nisin itself. Most notable was the activity observed against clinically relevant bacterial strains including MRSA and VRE. Experiments with membrane models indicate that these constructs operate via a lipid II-mediated mode of action without causing pore formation. A lipid II-dependent mechanism of action is further supported by antagonization assays wherein the addition of lipid II was found to effectively block the antibacterial activity of the nisin-derived lipopeptides.

  15. Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II

    DEFF Research Database (Denmark)

    Dahl, Morten; Bauer, Alison K; Arredouani, Mohamed

    2007-01-01

    Alveolar macrophages (AMs) express the class A scavenger receptors (SRAs) macrophage receptor with collagenous structure (MARCO) and scavenger receptor AI/II (SRA-I/II), which recognize oxidized lipids and provide innate defense against inhaled pathogens and particles. Increased MARCO expression......, consistent with SRA function in binding oxidized lipids. SR-AI/II-/- mice showed similar enhanced acute lung inflammation after beta-epoxide or another inhaled oxidant (aerosolized leachate of residual oil fly ash). In contrast, subacute ozone exposure did not enhance inflammation in SR-AI/II-/- versus SR-AI...

  16. Molecular Dynamics Simulations Reveal the Conformational Flexibility of Lipid II and Its Loose Association with the Defensin Plectasin in the Staphylococcus aureus Membrane

    DEFF Research Database (Denmark)

    Witzke, Sarah; Petersen, Michael; Carpenter, Timothy S.

    2016-01-01

    Lipid II is critical for peptidoglycan synthesis, which is the main component of the bacterial cell wall. Lipid II is a relatively conserved and important part of the cell wall biosynthesis pathway and is targeted by antibiotics such as the lantibiotics, which achieve their function by disrupting...... of Lipid II mediated by cations. In the presence of the defensin peptide plectasin, the conformational lability of Lipid II allows it to form loose complexes with the protein, via a number of different binding modes....... dynamics simulation study of the conformational dynamics of Lipid II within a detailed model of the Staphylococcus aureus cell membrane. We show that Lipid II is able to adopt a range of conformations, even within the packed lipidic environment of the membrane. Our simulations also reveal dimerization...

  17. Lipopolysaccharides from Yersinia pestis. Studies on lipid A of lipopolysaccharides I and II.

    Science.gov (United States)

    Dalla Venezia, N; Minka, S; Bruneteau, M; Mayer, H; Michel, G

    1985-09-01

    The chemical structure of the lipid A of lipopolysaccharide I and II from Yersinia pestis, strain EV 40, was studied. It consists of a (1 ---- 6), beta-linked D-glucosamine disaccharide which carries two phosphate groups; one phosphate is linked glycosidically with a glucosamine unit, the other one is linked to the non-reducing glucosamine. Various degradation methods combined with 31P nuclear magnetic resonance spectroscopy showed that the ester-bound phosphate group is linked to a 4-aminoarabinosyl residue and the glycosidically linked phosphate group is linked to a D-arabinofuranosyl residue in lipopolysaccharide II and to the phosphorylethanolamine in lipopolysaccharide I. The hydroxyl groups of the disaccharide are acylated by dodecanoic, hexadecenoic, 3-hydroxytetradecanoic and 3-dodecanoyloxytetradecanoic acids. The amino groups of the disaccharide carry 3-hydroxytetradecanoic and 3-dodecanoyloxytetradecanoic acids. In addition smaller amounts of 3-tetradecanoyloxyltetradecanoic and 3-hexadecanoyloxytetradecanoic acids are present in ester linkage.

  18. Two roles of thylakoid lipids in modifying the activity of herbicides which inhibit photosystem II

    Energy Technology Data Exchange (ETDEWEB)

    Kupatt, C.C. Jr.

    1985-01-01

    Thylakoid lipids may modify the activity of herbicides which inhibit electron transport at the Q/sub B/ protein of photosystem II in two ways: (1) lipids can act as a hydrophobic barrier to a binding site localized close to the loculus of the membrane, and (2) changes in lipid composition can reduce the ability of inhibitors to block electron transport, possibly due to a change in the conformation of the Q/sub B/ protein. The herbicide binding site was localized close to the locular side of the thylakoid membrane by determining the activity of a number of substituted phenylurea and s-triazine herbicides in inverted and non-inverted thylakoids. Quantitative structure-activity relationship analysis showed that inversion of thylakoids reduced the requirement of molecular lipophilicity deemed necessary for phenylurea activity in non-inverted membranes, whereas s-triazines exhibited no differences in the lipophilicity requirement in thylakoid membranes of either orientation. The binding affinity of /sup 14/C-diuron was reduced in bicarbonate-depleted thylakoids relative to reconstituted or control membranes, as is the case with atrazine binding. These observations support a model of the herbicide binding site containing both common and herbicide family specific binding domains. Thylakoids isolated either from detached lambs quarters (Chenopodium album L.) leaves, treated with SAN 6706, or from soybean (Glycine max L.), with norflurazon or pyrazon applied preemergence, exhibited decreased susceptibility to atrazine. The ability of lipid-modifying treatments to decrease the atrazine susceptibility of field-grown soybeans was also investigated.

  19. Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Adebiyi, Adebowale, E-mail: aadebiyi@uthsc.edu; Soni, Hitesh; John, Theresa A.; Yang, Fen

    2014-05-15

    Angiotensin II (ANG-II) receptors (AGTRs) contribute to renal physiology and pathophysiology, but the underlying mechanisms that regulate AGTR function in glomerular mesangium are poorly understood. Here, we show that AGTR1 is the functional AGTR subtype expressed in neonatal pig glomerular mesangial cells (GMCs). Cyclodextrin (CDX)-mediated cholesterol depletion attenuated cell surface AGTR1 protein expression and ANG-II-induced intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub i}) elevation in the cells. The COOH-terminus of porcine AGTR1 contains a caveolin (CAV)-binding motif. However, neonatal GMCs express CAV-1, but not CAV-2 and CAV-3. Colocalization and in situ proximity ligation assay detected an association between endogenous AGTR1 and CAV-1 in the cells. A synthetic peptide corresponding to the CAV-1 scaffolding domain (CSD) sequence also reduced ANG-II-induced [Ca{sup 2+}]{sub i} elevation in the cells. Real-time imaging of cell growth revealed that ANG-II stimulates neonatal GMC proliferation. ANG-II-induced GMC growth was attenuated by EMD 66684, an AGTR1 antagonist; BAPTA, a [Ca{sup 2+}]{sub i} chelator; KN-93, a Ca{sup 2+}/calmodulin-dependent protein kinase II inhibitor; CDX; and a CSD peptide, but not PD 123319, a selective AGTR2 antagonist. Collectively, our data demonstrate [Ca{sup 2+}]{sub i}-dependent proliferative effect of ANG-II and highlight a critical role for lipid raft microdomains in AGTR1-mediated signal transduction in neonatal GMCs. - Highlights: • AGTR1 is the functional AGTR subtype expressed in neonatal mesangial cells. • Endogenous AGTR1 associates with CAV-1 in neonatal mesangial cells. • Lipid raft disruption attenuates cell surface AGTR1 protein expression. • Lipid raft disruption reduces ANG-II-induced [Ca{sup 2+}]{sub i} elevation in neonatal mesangial cells. • Lipid raft disruption inhibits ANG-II-induced neonatal mesangial cell growth.

  20. Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation.

    Science.gov (United States)

    Zhang, Xingwang; Chen, Guijiang; Zhang, Tianpeng; Ma, Zhiguo; Wu, Baojian

    2014-01-01

    Lipid nanocarriers are becoming a versatile platform for oral delivery of lipophilic drugs. In this article, we aimed to explore the gastrointestinal behaviors of lipid nanoparticles and the effect of PEGylation on oral absorption of fenofibrate (FN), a Biopharmaceutics Classification System (BCS) II model drug. FN-loaded PEGylated lipid nanoparticles (FN-PLNs) were prepared by the solvent-diffusion method and characterized by particle size distribution, morphology, Fourier transform infrared spectroscopy, and drug release. Lipolytic experiments were performed to assess the resistance of lipid nanoparticles against pancreatic lipase. Pharmacokinetics was evaluated in rats after oral administration of FN preparations. The obtained FN-PLNs were 186.7 nm in size with an entrapment efficiency of >95%. Compared to conventional lipid nanoparticles, PLNs exhibited slower drug release in the lipase-containing medium, strikingly reduced mucin binding, and suppressed lipolysis in vitro. Further, oral absorption of FN was significantly enhanced using PLNs with relative bioavailability of 123.9% and 157.0% to conventional lipid nanoparticles and a commercial formulation (Lipanthyl(®)), respectively. It was demonstrated that reduced mucin trapping, suppressed lipolysis, and/or improved mucosal permeability were responsible for increased oral absorption. These results facilitated a better understanding of the in vivo fate of lipid nanoparticles, and suggested the potential of PLNs as oral carriers of BCS II drugs.

  1. ASSESSMENT OF SERUM LIPIDS IN TYPE II DIABETES MALE AND FEMALE PATIENTS

    Directory of Open Access Journals (Sweden)

    Annapurna

    2015-10-01

    Full Text Available BACKGROUND AND OBJECTIVE: Type II diabetes mellitus (T2DM often have both quantitative and qualitative abnormalities of lipoproteins that are responsible for increased incidence of microvascular and macrovascular complications. Incidence of coronary heart disease is three to four folds higher in patients with type 2 diabetes mellitus compared to non - diabetics. It has been proposed that the composition of lipid particles in diabetic dyslipidemia is more atherogenic than other types of dyslipidemia. This study was conducted to asses s serum lipid profile in type diabetes male and female patients. MATERIALS AND METHODS: This study was conducted on 50 T2DM patients with history more than ten yrs diabetes. Diabetic patients with overt complications and patients on drugs like diuretics, s teroids, oral contraceptives and beta blockers etc are excluded from study. 5 ml of whole blood was collected via vena puncture with the help of a disposable syringe in between 7.00am and 8.00am. Fasting plasma glucose and different Lipid fractions were es timated using standard procedure. All values were expressed as mean ± S.D. Statistical significance of differences between control and study groups were evaluated by student’s t test. A p - value less than 0.05 were considered as significant. RESULTS: The se rum total cholesterol, LDL cholesterol and triglycerides were significantly raised in both males and females . CONCLUSION: Hyperlipidaemia is a common finding among DM patients. DM patients should be screened and appropriate management should be instituted to reduce the risk of CHD and atherosclerosis

  2. Characterization of the P4-ATPase ATP8A2: Identification of Key Residues Involved in Catalysis and Lipid Transport

    DEFF Research Database (Denmark)

    Coleman, Jonathan Allan; Vestergaard, Anna Lindeløv; Molday, Robert S.;

    ATP8A2 is a P4-ATPase ("lipid flippase") highly expressed in the retina, brain, and testes. Previous studies in our laboratory have shown that ATP8A2 exists as a complex with its β-subunit CDC50A in retinal rod and cone photoreceptor cells and this complex preferentially transports phosphatidylse......ATP8A2 is a P4-ATPase ("lipid flippase") highly expressed in the retina, brain, and testes. Previous studies in our laboratory have shown that ATP8A2 exists as a complex with its β-subunit CDC50A in retinal rod and cone photoreceptor cells and this complex preferentially transports...... are likely the only species which are transported by P4-ATPases. These studies form a basis for further understanding lipid transport by this critical yet poorly understood class of P-type ATPases....

  3. Lipid Requirements for the Enzymatic Activity of MraY Translocases and in Vitro Reconstitution of the Lipid II Synthesis Pathway.

    Science.gov (United States)

    Henrich, Erik; Ma, Yi; Engels, Ina; Münch, Daniela; Otten, Christian; Schneider, Tanja; Henrichfreise, Beate; Sahl, Hans-Georg; Dötsch, Volker; Bernhard, Frank

    2016-01-29

    Screening of new compounds directed against key protein targets must continually keep pace with emerging antibiotic resistances. Although periplasmic enzymes of bacterial cell wall biosynthesis have been among the first drug targets, compounds directed against the membrane-integrated catalysts are hardly available. A promising future target is the integral membrane protein MraY catalyzing the first membrane associated step within the cytoplasmic pathway of bacterial peptidoglycan biosynthesis. However, the expression of most MraY homologues in cellular expression systems is challenging and limits biochemical analysis. We report the efficient production of MraY homologues from various human pathogens by synthetic cell-free expression approaches and their subsequent characterization. MraY homologues originating from Bordetella pertussis, Helicobacter pylori, Chlamydia pneumoniae, Borrelia burgdorferi, and Escherichia coli as well as Bacillus subtilis were co-translationally solubilized using either detergent micelles or preformed nanodiscs assembled with defined membranes. All MraY enzymes originating from Gram-negative bacteria were sensitive to detergents and required nanodiscs containing negatively charged lipids for obtaining a stable and functionally folded conformation. In contrast, the Gram-positive B. subtilis MraY not only tolerates detergent but is also less specific for its lipid environment. The MraY·nanodisc complexes were able to reconstitute a complete in vitro lipid I and lipid II forming pipeline in combination with the cell-free expressed soluble enzymes MurA-F and with the membrane-associated protein MurG. As a proof of principle for future screening platforms, we demonstrate the inhibition of the in vitro lipid II biosynthesis with the specific inhibitors fosfomycin, feglymycin, and tunicamycin.

  4. Nanostructured lipid carriers for incorporation of copper(II complexes to be used against Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Sato MR

    2017-03-01

    Full Text Available Mariana R Sato,1 João A Oshiro Junior,1 Rachel TA Machado,1 Paula C de Souza,2 Débora L Campos,2 Fernando R Pavan,2 Patricia B da Silva,1,* Marlus Chorilli1,* 1Department of Drugs and Medicines, Faculdade de Ciências Farmacêuticas, UNESP – Univ Estadual Paulista, Campus Araraquara, Araraquara, SP, Brazil; 2Department of Biological Sciences, Faculdade de Ciências Farmacêuticas, UNESP – Univ Estadual Paulista, Campus Araraquara, Araraquara, SP, Brazil *These authors contributed equally to this work Abstract: Tuberculosis (TB is a disease caused by Mycobacterium tuberculosis. Cessation of treatment before the recommended conclusion may lead to the emergence of multidrug-resistant strains. The aim of this study was to develop nanostructured lipid carriers (NLCs for use in the treatment of M. tuberculosis. The NLCs comprised the following lipid phase: 2.07% polyoxyethylene 40 stearate, 2.05% caprylic/capric triglyceride, and 0.88% polyoxyl 40 hydrogenated castor oil; the following aqueous phase: 3.50% poloxamer 407 (F1–F6, and 0.50% cetyltrimethylammonium bromide (F7–F12; and incorporated the copper(II complexes [CuCl2(INH2]·H2O (1, [Cu(NCS2(INH2]·5H2O (2, and [Cu(NCO2(INH2]·4H2O (3 to form compounds F11.1, F11.2, and F11.3, respectively. The mean diameter of F11, F11.1, F11.2, and F11.3 ranged from 111.27±21.86 to 134.25±22.72 nm, 90.27±12.97 to 116.46±9.17 nm, 112.4±10.22 to 149.3±15.82 nm, and 78.65±6.00 to 122.00±8.70 nm, respectively. The polydispersity index values for the NLCs ranged from 0.13±0.01 to 0.30±0.09. The NLCs showed significant changes in zeta potential, except for F11.2, with F11, F11.1, F11.2, and F11.3 ranging from 18.87±4.04 to 23.25±1.13 mV, 17.03±1.77 to 21.42±1.87 mV, 20.51±1.88 to 22.60±3.44 mV, and 17.80±1.96 to 25.25±7.78 mV, respectively. Atomic force microscopy confirmed the formation of nanoscale spherical particle dispersions by the NLCs. Differential scanning calorimetry determined

  5. Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

    Directory of Open Access Journals (Sweden)

    Zhang XW

    2014-11-01

    Full Text Available Xingwang Zhang,* Guijiang Chen,* Tianpeng Zhang, Zhiguo Ma, Baojian WuDivision of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: Lipid nanocarriers are becoming a versatile platform for oral delivery of lipophilic drugs. In this article, we aimed to explore the gastrointestinal behaviors of lipid nanoparticles and the effect of PEGylation on oral absorption of fenofibrate (FN, a Biopharmaceutics Classification System (BCS II model drug. FN-loaded PEGylated lipid nanoparticles (FN-PLNs were prepared by the solvent-diffusion method and characterized by particle size distribution, morphology, Fourier transform infrared spectroscopy, and drug release. Lipolytic experiments were performed to assess the resistance of lipid nanoparticles against pancreatic lipase. Pharmacokinetics was evaluated in rats after oral administration of FN preparations. The obtained FN-PLNs were 186.7 nm in size with an entrapment efficiency of >95%. Compared to conventional lipid nanoparticles, PLNs exhibited slower drug release in the lipase-containing medium, strikingly reduced mucin binding, and suppressed lipolysis in vitro. Further, oral absorption of FN was significantly enhanced using PLNs with relative bioavailability of 123.9% and 157.0% to conventional lipid nanoparticles and a commercial formulation (Lipanthyl®, respectively. It was demonstrated that reduced mucin trapping, suppressed lipolysis, and/or improved mucosal permeability were responsible for increased oral absorption. These results facilitated a better understanding of the in vivo fate of lipid nanoparticles, and suggested the potential of PLNs as oral carriers of BCS II drugs.Keywords: fenofibrate, lipid nanoparticles, PEGylation, oral bioavailability, absorption mechanism

  6. Effect of carnitine on lipid metabolism in the neonate. II. Carnitine addition to lipid infusion during prolonged total parenteral nutrition.

    Science.gov (United States)

    Orzali, A; Maetzke, G; Donzelli, F; Rubaltelli, F F

    1984-03-01

    The effect of carnitine administration on lipid metabolism and carnitine and acylcarnitine plasma values of newborn infants, given total parenteral nutrition for the first 7 days of life, was studied during a 4-hour infusion of Intralipid. An increase in plasma concentrations of total carnitine, free carnitine, and short-chain and long-chain acylcarnitine was found, but no significant change in triglycerides, free fatty acids, glycerol, or beta-hydroxybutyrate plasma values was noted, as compared with values obtained without carnitine administration. Moreover, the low free carnitine and short-chain and long-chain acylcarnitine plasma levels found in newborn infants after 7 days of total parenteral nutrition did not seem to impair the utilization of infused lipids. The results support the concept that the relation between the carnitine pool and lipid metabolism can be influenced by intravenous glucose infusion. Low carnitine plasma concentrations do not necessarily signify a depletion of body carnitine, and sufficient tissue carnitine concentrations can probably maintain good lipid utilization for an extended period.

  7. How to distinguish between the vacuum cleaner and flippase mechanisms of the LmrA multi-drug transporter in Lactococcus lactis

    NARCIS (Netherlands)

    Hofmeyr, JHS; Rohwer, JM; Snoep, JL; Westerhoff, HV; Konings, WN

    2002-01-01

    A numerical model of the LmrA multi-drug transport system of Lactococcus lactis is used to explore the possibility of distinguishing experimentally between two putative transport mechanisms, i.e., the vacuum-cleaner and the flippase mechanisms. This comparative model also serves as an example of num

  8. Food patterns associated with blood lipids are predictive of coronary heart disease: the Whitehall II study.

    Science.gov (United States)

    McNaughton, Sarah A; Mishra, Gita D; Brunner, Eric J

    2009-08-01

    Analysis of the epidemiological effects of overall dietary patterns offers an alternative approach to the investigation of the role of diet in CHD. We analysed the role of blood lipid-related dietary patterns using a two-step method to confirm the prospective association of dietary pattern with incident CHD. Analysis is based on 7314 participants of the Whitehall II study. Dietary intake was measured using a 127-item FFQ. Reduced rank regression (RRR) was used to derive dietary pattern scores using baseline serum total and HDL-cholesterol, and TAG levels as dependent variables. Cox proportional hazard regression was used to confirm the association between dietary patterns and incident CHD (n 243) over 15 years of follow-up. Increased CHD risk (hazard ratio (HR) for top quartile: 2.01 (95% CI 1.41, 2.85) adjusted for age, sex, ethnicity and energy misreporting) was observed with a diet characterised by high consumption of white bread, fried potatoes, sugar in tea and coffee, burgers and sausages, soft drinks, and low consumption of French dressing and vegetables. The diet-CHD relationship was attenuated after adjustment for employment grade and health behaviours (HR for top quartile: 1.81; 95% CI 1.26, 2.62), and further adjustment for blood pressure and BMI (HR for top quartile: 1.57; 95% CI 1.08, 2.27). Dietary patterns are associated with serum lipids and predict CHD risk after adjustment for confounders. RRR identifies dietary patterns using prior knowledge and focuses on the pathways through which diet may influence disease. The present study adds to the evidence that diet is an important risk factor for CHD.

  9. Nanostructured lipid carriers for incorporation of copper(II) complexes to be used against Mycobacterium tuberculosis

    Science.gov (United States)

    Sato, Mariana R; Oshiro Junior, João A; Machado, Rachel TA; de Souza, Paula C; Campos, Débora L; Pavan, Fernando R; da Silva, Patricia B; Chorilli, Marlus

    2017-01-01

    Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis. Cessation of treatment before the recommended conclusion may lead to the emergence of multidrug-resistant strains. The aim of this study was to develop nanostructured lipid carriers (NLCs) for use in the treatment of M. tuberculosis. The NLCs comprised the following lipid phase: 2.07% polyoxyethylene 40 stearate, 2.05% caprylic/capric triglyceride, and 0.88% polyoxyl 40 hydrogenated castor oil; the following aqueous phase: 3.50% poloxamer 407 (F1–F6), and 0.50% cetyltrimethylammonium bromide (F7–F12); and incorporated the copper(II) complexes [CuCl2(INH)2]·H2O (1), [Cu(NCS)2(INH)2]·5H2O (2), and [Cu(NCO)2(INH)2]·4H2O (3) to form compounds F11.1, F11.2, and F11.3, respectively. The mean diameter of F11, F11.1, F11.2, and F11.3 ranged from 111.27±21.86 to 134.25±22.72 nm, 90.27±12.97 to 116.46±9.17 nm, 112.4±10.22 to 149.3±15.82 nm, and 78.65±6.00 to 122.00±8.70 nm, respectively. The polydispersity index values for the NLCs ranged from 0.13±0.01 to 0.30±0.09. The NLCs showed significant changes in zeta potential, except for F11.2, with F11, F11.1, F11.2, and F11.3 ranging from 18.87±4.04 to 23.25±1.13 mV, 17.03±1.77 to 21.42±1.87 mV, 20.51±1.88 to 22.60±3.44 mV, and 17.80±1.96 to 25.25±7.78 mV, respectively. Atomic force microscopy confirmed the formation of nanoscale spherical particle dispersions by the NLCs. Differential scanning calorimetry determined the melting points of the constituents of the NLCs. The in vitro activity of copper(II) complex-loaded NLCs against M. tuberculosis H37Rv showed an improvement in the anti-TB activity of 55.4, 27.1, and 41.1 times the activity for complexes 1, 2, and 3, respectively. An in vivo acute toxicity study of complex-loaded NLCs demonstrated their reduced toxicity. The results suggest that NLCs may be a powerful tool to optimize the activity of copper(II) complexes against M. tuberculosis. PMID:28356717

  10. Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells.

    Science.gov (United States)

    Adebiyi, Adebowale; Soni, Hitesh; John, Theresa A; Yang, Fen

    2014-05-15

    Angiotensin II (ANG-II) receptors (AGTRs) contribute to renal physiology and pathophysiology, but the underlying mechanisms that regulate AGTR function in glomerular mesangium are poorly understood. Here, we show that AGTR1 is the functional AGTR subtype expressed in neonatal pig glomerular mesangial cells (GMCs). Cyclodextrin (CDX)-mediated cholesterol depletion attenuated cell surface AGTR1 protein expression and ANG-II-induced intracellular Ca(2+) ([Ca(2+)]i) elevation in the cells. The COOH-terminus of porcine AGTR1 contains a caveolin (CAV)-binding motif. However, neonatal GMCs express CAV-1, but not CAV-2 and CAV-3. Colocalization and in situ proximity ligation assay detected an association between endogenous AGTR1 and CAV-1 in the cells. A synthetic peptide corresponding to the CAV-1 scaffolding domain (CSD) sequence also reduced ANG-II-induced [Ca(2+)]i elevation in the cells. Real-time imaging of cell growth revealed that ANG-II stimulates neonatal GMC proliferation. ANG-II-induced GMC growth was attenuated by EMD 66684, an AGTR1 antagonist; BAPTA, a [Ca(2+)]i chelator; KN-93, a Ca(2+)/calmodulin-dependent protein kinase II inhibitor; CDX; and a CSD peptide, but not PD 123319, a selective AGTR2 antagonist. Collectively, our data demonstrate [Ca(2+)]i-dependent proliferative effect of ANG-II and highlight a critical role for lipid raft microdomains in AGTR1-mediated signal transduction in neonatal GMCs. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. A Crystal Structure of a Dimer of the Antibiotic Ramoplanin Illustrates Membrane Positioning and a Potential Lipid II Docking Interface

    Energy Technology Data Exchange (ETDEWEB)

    Hamburger, J.; Hoertz, A; Lee, A; Senturia, R; McCafferty, D; Loll, P

    2009-01-01

    The glycodepsipeptide antibiotic ramoplanin A2 is in late stage clinical development for the treatment of infections from Gram-positive pathogens, especially those that are resistant to first line antibiotics such as vancomycin. Ramoplanin A2 achieves its antibacterial effects by interfering with production of the bacterial cell wall; it indirectly inhibits the transglycosylases responsible for peptidoglycan biosynthesis by sequestering their Lipid II substrate. Lipid II recognition and sequestration occur at the interface between the extracellular environment and the bacterial membrane. Therefore, we determined the structure of ramoplanin A2 in an amphipathic environment, using detergents as membrane mimetics, to provide the most physiologically relevant structural context for mechanistic and pharmacological studies. We report here the X-ray crystal structure of ramoplanin A2 at a resolution of 1.4 {angstrom}. This structure reveals that ramoplanin A2 forms an intimate and highly amphipathic dimer and illustrates the potential means by which it interacts with bacterial target membranes. The structure also suggests a mechanism by which ramoplanin A2 recognizes its Lipid II ligand.

  12. Insight into invertebrate defensin mechanism of action: oyster defensins inhibit peptidoglycan biosynthesis by binding to lipid II.

    Science.gov (United States)

    Schmitt, Paulina; Wilmes, Miriam; Pugnière, Martine; Aumelas, André; Bachère, Evelyne; Sahl, Hans-Georg; Schneider, Tanja; Destoumieux-Garzón, Delphine

    2010-09-17

    Three oyster defensin variants (Cg-Defh1, Cg-Defh2, and Cg-Defm) were produced as recombinant peptides and characterized in terms of activities and mechanism of action. In agreement with their spectrum of activity almost specifically directed against Gram-positive bacteria, oyster defensins were shown here to be specific inhibitors of a bacterial biosynthesis pathway rather than mere membrane-active agents. Indeed, at lethal concentrations, the three defensins did not compromise Staphylococcus aureus membrane integrity but inhibited the cell wall biosynthesis as indicated by the accumulation of the UDP-N-acetylmuramyl-pentapeptide cell wall precursor. In addition, a combination of antagonization assays, thin layer chromatography, and surface plasmon resonance measurements showed that oyster defensins bind almost irreversibly to the lipid II peptidoglycan precursor, thereby inhibiting the cell wall biosynthesis. To our knowledge, this is the first detailed analysis of the mechanism of action of antibacterial defensins produced by invertebrates. Interestingly, the three defensins, which were chosen as representative of the oyster defensin molecular diversity, bound differentially to lipid II. This correlated with their differential antibacterial activities. From our experimental data and the analysis of oyster defensin sequence diversity, we propose that oyster defensin activity results from selective forces that have conserved residues involved in lipid II binding and diversified residues at the surface of oyster defensins that could improve electrostatic interactions with the bacterial membranes.

  13. Plasma membrane aminoglycerolipid flippase function is required for signaling competence in the yeast mating pheromone response pathway.

    Science.gov (United States)

    Sartorel, Elodie; Barrey, Evelyne; Lau, Rebecca K; Thorner, Jeremy

    2015-01-01

    The class 4 P-type ATPases ("flippases") maintain membrane asymmetry by translocating phosphatidylethanolamine and phosphatidylserine from the outer leaflet to the cytosolic leaflet of the plasma membrane. In Saccharomyces cerevisiae, five related gene products (Dnf1, Dnf2, Dnf3, Drs2, and Neo1) are implicated in flipping of phosphatidylethanolamine, phosphatidylserine, and phosphatidylcholine. In MAT A: cells responding to α-factor, we found that Dnf1, Dnf2, and Dnf3, as well as the flippase-activating protein kinase Fpk1, localize at the projection ("shmoo") tip where polarized growth is occurring and where Ste5 (the central scaffold protein of the pheromone-initiated MAPK cascade) is recruited. Although viable, a MAT A: dnf1∆ dnf2∆ dnf3∆ triple mutant exhibited a marked decrease in its ability to respond to α-factor, which we could attribute to pronounced reduction in Ste5 stability resulting from an elevated rate of its Cln2⋅Cdc28-initiated degradation. Similarly, a MAT A: dnf1∆ dnf3∆ drs2∆ triple mutant also displayed marked reduction in its ability to respond to α-factor, which we could attribute to inefficient recruitment of Ste5 to the plasma membrane due to severe mislocalization of the cellular phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate pools. Thus proper remodeling of plasma membrane aminoglycerolipids and phosphoinositides is necessary for efficient recruitment, stability, and function of the pheromone signaling apparatus. © 2015 Sartorel et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  14. Composition of MHC class II-enriched lipid microdomains is modified during maturation of primary dendritic cells.

    Science.gov (United States)

    Setterblad, Niclas; Roucard, Corinne; Bocaccio, Claire; Abastado, Jean-Pierre; Charron, Dominique; Mooney, Nuala

    2003-07-01

    Dendritic cells (DCs) are the most potent antigen presenting cells. Major histocompatibility complex (MHC) class II molecule expression changes with maturation; immature DCs concentrate MHC class II molecules intracellularly, whereas maturation increases surface expression of MHC class II and costimulatory molecules to optimize antigen presentation. Signal transduction via MHC class II molecules localized in lipid microdomains has been described in B lymphocytes and in the THP-1 monocyte cell line. We have characterized MHC class II molecules throughout human DC maturation with particular attention to their localization in lipid-rich microdomains. Only immature DCs expressed empty MHC class II molecules, and maturation increased the level of peptide-bound heterodimers. Ligand binding to surface human leukocyte antigen (HLA)-DR induced rapid internalization in immature DCs. The proportion of cell-surface detergent-insoluble glycosphingolipid-enriched microdomain-clustered HLA-DR was higher in immature DCs despite the higher surface expression of HLA-DR in mature DCs. Constituents of HLA-DR containing microdomains included the src kinase Lyn and the cytoskeletal protein tubulin in immature DCs. Maturation modified the composition of the HLA-DR-containing microdomains to include protein kinase C (PKC)-delta, Lyn, and the cytoskeletal protein actin, accompanied by the loss of tubulin. Signaling via HLA-DR redistributed HLA-DR and -DM and PKC-delta as well as enriching the actin content of mature DC microdomains. The increased expression of HLA-DR as a result of DC maturation was therefore accompanied by modification of the spatial organization of HLA-DR. Such regulation could contribute to the distinct responses induced by ligand binding to MHC class II molecules in immature versus mature DCs.

  15. Specific binding of nisin to the peptidoglycan precursor lipid II combines pore formation and inhibition of cell wall biosynthesis for potent antibiotic activity

    NARCIS (Netherlands)

    Wiedemann, [No Value; Breukink, E; van Kraaij, C; Kuipers, OP; Bierbaum, G; de Kruijff, B; Sahl, HA

    2001-01-01

    Unlike numerous pore-forming amphiphilic peptide antibiotics, the lantibiotic nisin is active in nanomolar concentrations, which results from its ability to use the Lipid-bound cell wall precursor lipid II as a docking molecule for subsequent pore formation. Here we use genetically engineered nisin

  16. Ca2+ -regulated lysosome fusion mediates angiotensin II-induced lipid raft clustering in mesenteric endothelial cells.

    Science.gov (United States)

    Han, Wei-Qing; Chen, Wen-Dong; Zhang, Ke; Liu, Jian-Jun; Wu, Yong-Jie; Gao, Ping-Jin

    2016-04-01

    It has been reported that intracellular Ca2+ is involved in lysosome fusion and membrane repair in skeletal cells. Given that angiotensin II (Ang II) elicits an increase in intracellular Ca2+ and that lysosome fusion is a crucial mediator of lipid raft (LR) clustering, we hypothesized that Ang II induces lysosome fusion and activates LR formation in rat mesenteric endothelial cells (MECs). We found that Ang II acutely increased intracellular Ca2+ content, an effect that was inhibited by the extracellular Ca2+ chelator ethylene glycol tetraacetic acid (EGTA) and the inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release inhibitor 2-aminoethoxydiphenyl borate (2-APB). Further study showed that EGTA almost completely blocked Ang II-induced lysosome fusion, the translocation of acid sphingomyelinase (ASMase) to LR clusters, ASMase activation and NADPH (nicotinamide adenine dinucleotide phosphate) oxidase activation. In contrast, 2-APB had a slight inhibitory effect. Functionally, both the lysosome inhibitor bafilomycin A1 and the ASMase inhibitor amitriptyline reversed Ang II-induced impairment of vasodilation. We conclude that Ca2+ -regulated lysosome fusion mediates the Ang II-induced regulation of the LR-redox signaling pathway and mesenteric endothelial dysfunction.

  17. Apolipoprotein A-II Plus Lipid Emulsion Enhance Cell Growth via SR-B1 and Target Pancreatic Cancer In Vitro and In Vivo.

    Science.gov (United States)

    Julovi, Sohel M; Xue, Aiqun; Thanh LE, Thao N; Gill, Anthony J; Bulanadi, Jerikho C; Patel, Mili; Waddington, Lynne J; Rye, Kerry-Anne; Moghaddam, Minoo J; Smith, Ross C

    2016-01-01

    Apolipoprotein A-II (ApoA-II) is down regulated in the sera of pancreatic ductal adenocarcinoma (PDAC) patients, which may be due to increase utilization of high density lipoprotein (HDL) lipid by pancreatic cancer tissue. This study examined the influence of exogenous ApoA-II on lipid uptake and cell growth in pancreatic cancer (PC) both in vitro and in vivo. Cryo transmission electron microscopy (TEM) examined ApoA-II's influence on morphology of SMOFLipid emulsion. The influence of ApoA-II on proliferation of cancer cell lines was determined by incubating them with lipid+/-ApoA-II and anti-SR-B1 antibody. Lipid was labeled with the fluorophore, DiD, to trace lipid uptake by cancer cells in vitro by confocal microscopy and in vivo in PDAC patient derived xenograft tumours (PDXT) by fluorescence imaging. Scavenger receptor class B type-1(SR-B1) expression in PDAC cell lines and in PDAC PDXT was measured by western blotting and immunohistochemistry, respectively. ApoA-II spontaneously converted lipid emulsion into very small unilamellar rHDL like vesicles (rHDL/A-II) and enhanced lipid uptake in PANC-1, CFPAC-1 and primary tumour cells as shown by confocal microscopy. SR-B1 expression was 13.2, 10.6, 3.1 and 2.3 fold higher in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cell lines than the normal pancreatic cell line (HPDE6) and 3.7 fold greater in PDAC tissue than in normal pancreas. ApoA-II plus lipid significantly increased the uptake of labeled lipid and promoted cell growth in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cells which was inhibited by anti SR-B1 antibody. Further, ApoA-II increased the uptake of lipid in xenografts by 3.4 fold. Our data suggest that ApoA-II enhance targeting potential of lipid in pancreatic cancer which may have imaging and drug delivery potentialities.

  18. Apolipoprotein A-II Plus Lipid Emulsion Enhance Cell Growth via SR-B1 and Target Pancreatic Cancer In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Sohel M Julovi

    Full Text Available Apolipoprotein A-II (ApoA-II is down regulated in the sera of pancreatic ductal adenocarcinoma (PDAC patients, which may be due to increase utilization of high density lipoprotein (HDL lipid by pancreatic cancer tissue. This study examined the influence of exogenous ApoA-II on lipid uptake and cell growth in pancreatic cancer (PC both in vitro and in vivo.Cryo transmission electron microscopy (TEM examined ApoA-II's influence on morphology of SMOFLipid emulsion. The influence of ApoA-II on proliferation of cancer cell lines was determined by incubating them with lipid+/-ApoA-II and anti-SR-B1 antibody. Lipid was labeled with the fluorophore, DiD, to trace lipid uptake by cancer cells in vitro by confocal microscopy and in vivo in PDAC patient derived xenograft tumours (PDXT by fluorescence imaging. Scavenger receptor class B type-1(SR-B1 expression in PDAC cell lines and in PDAC PDXT was measured by western blotting and immunohistochemistry, respectively.ApoA-II spontaneously converted lipid emulsion into very small unilamellar rHDL like vesicles (rHDL/A-II and enhanced lipid uptake in PANC-1, CFPAC-1 and primary tumour cells as shown by confocal microscopy. SR-B1 expression was 13.2, 10.6, 3.1 and 2.3 fold higher in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cell lines than the normal pancreatic cell line (HPDE6 and 3.7 fold greater in PDAC tissue than in normal pancreas. ApoA-II plus lipid significantly increased the uptake of labeled lipid and promoted cell growth in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cells which was inhibited by anti SR-B1 antibody. Further, ApoA-II increased the uptake of lipid in xenografts by 3.4 fold.Our data suggest that ApoA-II enhance targeting potential of lipid in pancreatic cancer which may have imaging and drug delivery potentialities.

  19. Effect of lipid matrix and cytoskeleton proteins on Ca2+-activated K+ channels in erythrocytes of alcoholic and II type diabetes mellitus patients.

    Science.gov (United States)

    Prokop'eva, V D; Petrova, I V; Sitozhevskii, A V; Kremeno, S V; Koryukin, V I; Baskakov, M B; Bokhan, N A; Novitskii, V V

    2002-10-01

    We studied the effect of changes in erythrocyte volume and irreversible thermal denaturation of cytoskeleton proteins and lipid matrix on activity of Ca(2+)-activated K+ channels in erythrocytes of alcoholic and patients with II type diabetes mellitus. Changes in Ca(2+)-dependent potassium permeability of erythrocyte membrane in alcoholic patients and patients with II type diabetes mellitus are related to modification of cytoskeleton, rather than to changes in lipid matrix.

  20. Opt2 mediates the exposure of phospholipids during cellular adaptation to altered lipid asymmetry.

    Science.gov (United States)

    Yamauchi, Saori; Obara, Keisuke; Uchibori, Kenya; Kamimura, Akiko; Azumi, Kaoru; Kihara, Akio

    2015-01-01

    Plasma membrane lipid asymmetry is important for various membrane-associated functions and is regulated by membrane proteins termed flippases and floppases. The Rim101 pathway senses altered lipid asymmetry in the yeast plasma membrane. The mutant lem3Δ cells, in which lipid asymmetry is disturbed owing to the inactivation of the plasma membrane flippases, showed a severe growth defect when the Rim101 pathway was impaired. To identify factors involved in the Rim101-pathway-dependent adaptation to altered lipid asymmetry, we performed DNA microarray analysis and found that Opt2 induced by the Rim101 pathway plays an important role in the adaptation to altered lipid asymmetry. Biochemical investigation of Opt2 revealed its localization to the plasma membrane and the Golgi, and provided several lines of evidence for the Opt2-mediated exposure of phospholipids. In addition, Opt2 was found to be required for the maintenance of vacuolar morphology and polarized cell growth. These results suggest that Opt2 is a novel factor involved in cell homeostasis by regulating lipid asymmetry.

  1. Composition of cellular membranes in the pancreas of the guinea pig. II. Lipids.

    Science.gov (United States)

    Meldolesi, J; Jamieson, J D; Palade, G E

    1971-04-01

    The lipid composition of rough and smooth microsomal membranes, zymogen granule membranes, and a plasmalemmal fraction from the guinea pig pancreatic exocrine cell has been determined. As a group, membranes of the smooth variety (i.e., smooth microsomes, zymogen granule membranes, and the plasmalemma) were similar in their content of phospholipids, cholesterol and neutral lipids, and in the ratio of total lipids to membrane proteins. In contrast, rough microsomal membranes contained much less sphingomyelin and cholesterol and possessed a smaller lipid/protein ratio. All membrane fractions were unusually high in their content of lysolecithin (up to approximately 20% of the total phospholipids) and of neutral lipids, especially fatty acids. The lysolecithin content was shown to be due to the hydrolysis of membrane lecithin by pancreatic lipase; the fatty acids, liberated by the action of lipase on endogenous triglyceride stores, are apparently scavenged by the membranes from the suspending media. Similar artifactually high levels of lysolecithin and fatty acids were noted in hepatic microsomes incubated with pancreatic postmicrosomal supernatant. E 600, an inhibitor of lipase, largely prevented the appearance of lysolecithin and fatty acids in pancreatic microsomes and in liver microsomes treated with pancreatic supernatant.

  2. Metallothionein-II Inhibits Lipid Peroxidation and Improves Functional Recovery after Transient Brain Ischemia and Reperfusion in Rats

    Directory of Open Access Journals (Sweden)

    Araceli Diaz-Ruiz

    2014-01-01

    Full Text Available After transient cerebral ischemia and reperfusion (I/R, damaging mechanisms, such as excitotoxicity and oxidative stress, lead to irreversible neurological deficits. The induction of metallothionein-II (MT-II protein is an endogenous mechanism after I/R. Our aim was to evaluate the neuroprotective effect of MT-II after I/R in rats. Male Wistar rats were transiently occluded at the middle cerebral artery for 2 h, followed by reperfusion. Rats received either MT (10 μg per rat i.p. or vehicle after ischemia. Lipid peroxidation (LP was measured 22 h after reperfusion in frontal cortex and hippocampus; also, neurological deficit was evaluated after ischemia, using the Longa scoring scale. Infarction area was analyzed 72 hours after ischemia. Results showed increased LP in frontal cortex (30.7% and hippocampus (26.4%, as compared to control group; this effect was fully reversed by MT treatment. Likewise, we also observed a diminished neurological deficit assessed by the Longa scale in those animals treated with MT compared to control group values. The MT-treated group showed a significant (P<0.05 reduction of 39.9% in the infarction area, only at the level of hippocampus, as compared to control group. Results suggest that MT-II may be a novel neuroprotective treatment to prevent ischemia injury.

  3. Understanding physical developer (PD): Part I--Is PD targeting lipids?

    Science.gov (United States)

    de la Hunty, Mackenzie; Moret, Sébastien; Chadwick, Scott; Lennard, Chris; Spindler, Xanthe; Roux, Claude

    2015-12-01

    Physical developer (PD) is a fingermark development technique that involves the selective reduction of silver onto fingermark residue. PD can develop marks on porous substrates even if they have been wet, leading to the logical, long held belief that the reagent targets the water insoluble constituents in the fingermark residue. The present research has tested this hypothesis as part of a broader study that aims to identify the targets of physical developer. Spot tests of some fatty acids, cholesterol and squalene, treated with PD, showed that only cholesterol produced significant silver deposition. PD is known to be particularly effective on aged marks, however cholesterol degrades over time. These observations indicate that PD reactivity with fingermarks cannot solely be due to the presence of cholesterol. Fingermarks were deposited on paper and washed with various organic solvents before being treated with PD. PD effectiveness was intermittent on both solvent washed and unwashed sides of both natural and groomed marks; however, it was seen to effectively develop groomed samples that had been exposed to common lipid extraction solvents, shown to have removed the lipids by visualisation using the lipid stain Nile red. PD effectiveness was most affected by exposure of samples to solvents that could dissolve water soluble components, showing that the removal of these constituents (by either water, or other solvents) decreases the amount of silver deposited on the fingermark residue by the working solution. Close observation of PD developed samples showed variation in silver deposition uniformity when comparing a developed ridge to a pore site located on that ridge. Some samples showed an absence of silver, and other showed an increase of silver at pore locations. This indicates that the material excreted by the pores on the finger has an effect on silver deposition, suggesting that PD may be specifically targeting eccrine constituents that are present along the

  4. Review: P4-ATPases as Phospholipid Flippases-Structure, Function, and Enigmas

    DEFF Research Database (Denmark)

    Andersen, Jens P; Vestergaard, Anna L; Mikkelsen, Stine A

    2016-01-01

    P4-ATPases comprise a family of P-type ATPases that actively transport or flip phospholipids across cell membranes. This generates and maintains membrane lipid asymmetry, a property essential for a wide variety of cellular processes such as vesicle budding and trafficking, cell signaling, blood...... is highlighted by the finding that genetic defects in two P4-ATPases ATP8A2 and ATP8B1 are associated with severe human disorders. Recent studies have provided insight into how P4-ATPases translocate phospholipids across membranes. P4-ATPases form a phosphorylated intermediate at the aspartate of the P......-type ATPase signature sequence, and dephosphorylation is activated by the lipid substrate being flipped from the exoplasmic to the cytoplasmic leaflet similar to the activation of dephosphorylation of Na+/K+-ATPase by exoplasmic K+. How the phospholipid is translocated can be understood in terms...

  5. Nutritional and biochemical properties of human milk: II. Lipids, micronutrients, and bioactive factors.

    Science.gov (United States)

    Rodriguez-Palmero, M; Koletzko, B; Kunz, C; Jensen, R

    1999-06-01

    Human milk lipids contain preformed LCPUFA in considerable amounts, which serve as precursors for the formation of prostaglandins, prostacyclins, and other lipid mediators, as well as essential components in membrane-rich tissues (such as the brain and the retina), thus affecting functional outcomes. Besides a balanced nutrient composition and a number of conditionally essential nutrients, human milk provides different types and classes of bioactive factors, such as enzymes, hormones, and growth factors, many of which appear to have a role in supporting infantile growth and development. The bioactive agents include antimicrobial factors (e.g., secretory IgA, oligosaccharides, FA); anti-inflammatory agents; transporters (e.g., lactoferrin); and digestive enzymes (e.g., BSSL). Several nonpeptide hormones (thyroid hormones, cortisol, progesterone, pregnanediol, estrogens, and artificial contraceptive) and peptide hormones and growth factors (erythropoietin, hHG, gonadotropin-releasing hormone, epidermal growth factor insulin, insulin-like growth factor-I, nerve growth factor, transforming growth factor-alpha, gastrointestinal regulatory peptides and thyroid-parathyroid hormones) have been isolated and quantitated in human milk. Some of these components are also involved in the maturation of the gastrointestinal tract of the infant. In addition to the passive benefits provided by human milk, several data support the hypothesis that breastfeeding promotes the development of the infant's own immune system, which might confer long-term benefits for the newborn infant. The risk of IDDM, Crohn's disease, and atopic disease is lower in individuals who had been breastfed during infancy. Areas of major interest in human milk research include the study of human milk synthesis and the contributions of dietary composition and maternal metabolism to human milk composition, infantile utilization of human milk components, and the study of bioactive components, such as

  6. Identification and in vitro analysis of the GatD/MurT enzyme-complex catalyzing lipid II amidation in Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Daniela Münch

    2012-01-01

    Full Text Available The peptidoglycan of Staphylococcus aureus is characterized by a high degree of crosslinking and almost completely lacks free carboxyl groups, due to amidation of the D-glutamic acid in the stem peptide. Amidation of peptidoglycan has been proposed to play a decisive role in polymerization of cell wall building blocks, correlating with the crosslinking of neighboring peptidoglycan stem peptides. Mutants with a reduced degree of amidation are less viable and show increased susceptibility to methicillin. We identified the enzymes catalyzing the formation of D-glutamine in position 2 of the stem peptide. We provide biochemical evidence that the reaction is catalyzed by a glutamine amidotransferase-like protein and a Mur ligase homologue, encoded by SA1707 and SA1708, respectively. Both proteins, for which we propose the designation GatD and MurT, are required for amidation and appear to form a physically stable bi-enzyme complex. To investigate the reaction in vitro we purified recombinant GatD and MurT His-tag fusion proteins and their potential substrates, i.e. UDP-MurNAc-pentapeptide, as well as the membrane-bound cell wall precursors lipid I, lipid II and lipid II-Gly₅. In vitro amidation occurred with all bactoprenol-bound intermediates, suggesting that in vivo lipid II and/or lipid II-Gly₅ may be substrates for GatD/MurT. Inactivation of the GatD active site abolished lipid II amidation. Both, murT and gatD are organized in an operon and are essential genes of S. aureus. BLAST analysis revealed the presence of homologous transcriptional units in a number of gram-positive pathogens, e.g. Mycobacterium tuberculosis, Streptococcus pneumonia and Clostridium perfringens, all known to have a D-iso-glutamine containing PG. A less negatively charged PG reduces susceptibility towards defensins and may play a general role in innate immune signaling.

  7. A Nanostructured Lipid System as a Strategy to Improve the in Vitro Antibacterial Activity of Copper(II Complexes

    Directory of Open Access Journals (Sweden)

    Patricia B. da Silva

    2015-12-01

    Full Text Available The aim of this study was to construct a nanostructured lipid system as a strategy to improve the in vitro antibacterial activity of copper(II complexes. New compounds with the general formulae [CuX2(INH2]·nH2O (X = Cl− and n = 1 (1; X = NCS− and n = 5 (2; X = NCO− and n = 4 (3; INH = isoniazid, a drug widely used to treat tuberculosis derived from the reaction between the copper(II chloride and isoniazid in the presence or absence of pseudohalide ions (NCS− or NCO− were synthesized and characterized by infrared spectrometry, electronic absorption spectroscopy, electron paramagnetic resonance (EPR spectroscopy, elemental analysis, melting points and complexometry with 2,2′,2′′,2′′′-(Ethane-1,2-diyldinitrilotetraacetic acid (EDTA. The characterization techniques allowed us to confirm the formation of the copper(II complexes. The Cu(II complexes were loaded into microemulsion (MEs composed of 10% phase oil (cholesterol, 10% surfactant [soy oleate and Brij® 58 (1:2] and 80% aqueous phase (phosphate buffer pH = 7.4 prepared by sonication. The Cu(II complex-loaded MEs displayed sizes ranging from 158.0 ± 1.060 to 212.6 ± 1.539 nm, whereas the polydispersity index (PDI ranged from 0.218 ± 0.007 to 0.284 ± 0.034. The antibacterial activity of the free compounds and those that were loaded into the MEs against Staphylococcus aureus ATCC® 25923 and Escherichia coli ATCC® 25922, as evaluated by a microdilution technique, and the cytotoxicity index (IC50 against the Vero cell line (ATCC® CCL-81TM were used to calculate the selectivity index (SI. Among the free compounds, only compound 2 (MIC 500 μg/mL showed activity for S. aureus. After loading the compounds into the MEs, the antibacterial activity of compounds 1, 2 and 3 was significantly increased against E. coli (MIC’s 125, 125 and 500 μg/mL, respectively and S. aureus (MICs 250, 500 and 125 μg/mL, respectively. The loaded compounds were less toxic against the Vero

  8. A Nanostructured Lipid System as a Strategy to Improve the in Vitro Antibacterial Activity of Copper(II) Complexes.

    Science.gov (United States)

    Silva, Patricia B da; Bonifácio, Bruna V; Frem, Regina C G; Godoy Netto, Adelino V; Mauro, Antonio E; Ferreira, Ana M da Costa; Lopes, Erica de O; Raddi, Maria S G; Bauab, Tais M; Pavan, Fernando R; Chorilli, Marlus

    2015-12-16

    The aim of this study was to construct a nanostructured lipid system as a strategy to improve the in vitro antibacterial activity of copper(II) complexes. New compounds with the general formulae [CuX₂(INH)₂]·nH₂O (X = Cl(-) and n = 1 (1); X = NCS(-) and n = 5 (2); X = NCO(-) and n = 4 (3); INH = isoniazid, a drug widely used to treat tuberculosis) derived from the reaction between the copper(II) chloride and isoniazid in the presence or absence of pseudohalide ions (NCS(-) or NCO(-)) were synthesized and characterized by infrared spectrometry, electronic absorption spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, elemental analysis, melting points and complexometry with 2,2',2'',2'''-(Ethane-1,2-diyldinitrilo)tetraacetic acid (EDTA). The characterization techniques allowed us to confirm the formation of the copper(II) complexes. The Cu(II) complexes were loaded into microemulsion (MEs) composed of 10% phase oil (cholesterol), 10% surfactant [soy oleate and Brij® 58 (1:2)] and 80% aqueous phase (phosphate buffer pH = 7.4) prepared by sonication. The Cu(II) complex-loaded MEs displayed sizes ranging from 158.0 ± 1.060 to 212.6 ± 1.539 nm, whereas the polydispersity index (PDI) ranged from 0.218 ± 0.007 to 0.284 ± 0.034. The antibacterial activity of the free compounds and those that were loaded into the MEs against Staphylococcus aureus ATCC® 25923 and Escherichia coli ATCC® 25922, as evaluated by a microdilution technique, and the cytotoxicity index (IC50) against the Vero cell line (ATCC® CCL-81(TM)) were used to calculate the selectivity index (SI). Among the free compounds, only compound 2 (MIC 500 μg/mL) showed activity for S. aureus. After loading the compounds into the MEs, the antibacterial activity of compounds 1, 2 and 3 was significantly increased against E. coli (MIC's 125, 125 and 500 μg/mL, respectively) and S. aureus (MICs 250, 500 and 125 μg/mL, respectively). The loaded compounds were less toxic against the Vero

  9. Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye - Part II - Ocular drug-loaded lipid nanoparticles.

    Science.gov (United States)

    Sánchez-López, E; Espina, M; Doktorovova, S; Souto, E B; García, M L

    2017-01-01

    In the recent decades, various controlled delivery systems have been introduced with the aim to improve solubility, stability and bioavailability of poorly absorbed drugs. Among all, lipid nanoparticles gather interesting properties as drug or gene delivery carriers. These systems, composed either of solid lipids (SLN) or of solid and liquid lipids (NLC) stabilized with surfactants, combine the advantages of other colloidal particles such as polymeric nanoparticles, fat emulsions and liposomes avoiding their main disadvantages. Lipid nanoparticles represent an interesting approach for eye drug delivery as they can improve the corneal absorption of drugs enhancing their bioavailability. The Generally Recognized as Safe status of formulation excipients, the scaling-up facilities and the possibility of sterilization, make them suitable for industrial production. In this review, the latest findings, potential applications, and challenges related to the use of lipid nanoparticles for ocular drug delivery are comprehensively discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. The processes of lipid peroxidation in the cells of Chlorobium limicola IMV K-8 under the influence of copper (II sulphate

    Directory of Open Access Journals (Sweden)

    T. B. Segin

    2015-12-01

    Full Text Available The effect of stressors, including heavy metal ions such as Cu2+, promotes activation of free radical processes in the cells of microorganisms, which causes changes in their physiological and biochemical properties and the structure of bacterial membranes. The aim of this work was to assess the influence of copper (II sulphate on intensity of lipid peroxidation (LPO of Chlorobium limicola IMV K-8 by measuring the content of primary (conjugated dienes and lipid hydroperoxides and secondary lipid peroxidation products (TBA-reactive products. Microorganisms were cultivated at a temperature of 28 °C in GSB cultivation medium with exposure to light of wavelength 700–800 nm and intensity 40 lux. A suspension of C. limicola ІМV К-8 cells in the phase of exponential growth was treated for one hour with metal salt solution in concentrations 0.05–0.50 mM for investigation of the influence of copper (II sulphate on its physiological and biochemical properties. The control samples did not contain any copper (II sulphate. Biomass was determined by turbidity of diluted cell suspension by application of photoelectric colorimeter KFK-3. A mixture of n-heptane and isopropyl alcohol was added into cell-free extract for conjugated dienes determination. The samples were incubated at room temperature and centrifuged. Water was added into the supernatant and the samples were stirred. Ethanol was added to the heptanes phase and adsorption was measured at 233 nm. The content of lipid hydroperoxides was determined by a method based on protein precipitation by trichloroacetic acid followed by addition of ammonium thiocyanate. The concentration of TBA-reactive products in the cell-free extracts was determined by color reaction with malondialdehyde and thiobarbituric acid exposed to high temperature and acidity of the medium, which causes formation of trimetinic adduct with maximal absorption at 532 nm. It was shown that when CuSO4 was added to the incubation

  11. Effect of Vit C Supplement on Fasting Blood Glucose and Plasma Lipid Level in Type II Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Mehri Delvarianzadeh

    2008-01-01

    Full Text Available Introduction: Diabetic people are more at risk of diseases such as vascular, kidneys and eye diseases, compared with normal people. Since Vit C competitively replaces glucose in most chemical reactions; so inhibit on non enzymatic glycosylation such as hemoglobin and lipoproteins, it seems that Vit C can be effective to prevent diabetic complications .In this study effect of Vit C supplements on blood sugar and fats level in type II diabetic patients was investigated. Methods: This study was conducted as a clinical trial using paired random sampling on 136 type II diabetic patients. At first, the patients weights, age, type of diet were recorded .Then their fasting blood glucose (FBS, glycosylated hemoglobin (HbAIC, Cholesterol, triglyceride, HDL and LDL were measured. After that the patients were divided in two randomized groups. The first group (control was subject of administration of Vit C supplement (1250 mg, 5 times a day, for a period of 3 months and the second group received placebo. Data were analyzed by paired t- test and SPSS Software. Results: In this study most of patients were women (62.2% of control group and 64.7% of placebo group. The mean age between the control group and placebo group were reported 51.2 ± 6.8 and 50.37± 9.71 years respectively. At the end of study , after 3 months of administration of Vit C supplement to control group, the mean concentration of FBS, LDL triglyceride Cholesterol and glycosylated hemoglobin has been reduced significantly with respect to the placebo group and the mean value of HDL has been increased as well. Conclusion: The finding shows that Vit C supplements might reduce the amount of glucose, lipids and glycosylated hemoglobin in patients with type 2 diabetes. Therefore, its consumption in diabetic patients can be recommended and as a result patient complications will be significantly reduced.

  12. Prevention of non-communicable disease in a population in nutrition transition: Tehran Lipid and Glucose Study phase II

    Directory of Open Access Journals (Sweden)

    Hedayati Mehdi

    2009-01-01

    Full Text Available Abstract Background The Tehran Lipid and Glucose Study (TLGS is a long term integrated community-based program for prevention of non-communicable disorders (NCD by development of a healthy lifestyle and reduction of NCD risk factors. The study begun in 1999, is ongoing, to be continued for at least 20 years. A primary survey was done to collect baseline data in 15005 individuals, over 3 years of age, selected from cohorts of three medical heath centers. A questionnaire for past medical history and data was completed during interviews; blood pressure, pulse rate, and anthropometrical measurements and a limited physical examination were performed and lipid profiles, fasting blood sugar and 2-hours-postload-glucose challenge were measured. A DNA bank was also collected. For those subjects aged over 30 years, Rose questionnaire was completed and an electrocardiogram was taken. Data collected were directly stored in computers as database software- computer assisted system. The aim of this study is to evaluate the feasibility and effectiveness of lifestyle modification in preventing or postponing the development of NCD risk factors and outcomes in the TLGS population. Design and methods In phase II of the TLGS, lifestyle interventions were implemented in 5630 people and 9375 individuals served as controls. Primary, secondary and tertiary interventions were designed based on specific target groups including schoolchildren, housewives, and high-risk persons. Officials of various sectors such as health, education, municipality, police, media, traders and community leaders were actively engaged as decision makers and collaborators. Interventional strategies were based on lifestyle modifications in diet, smoking and physical activity through face-to-face education, leaflets & brochures, school program alterations, training volunteers as health team and treating patients with NCD risk factors. Collection of demographic, clinical and laboratory data will be

  13. Annotated compound data for modulators of detergent-solubilised or lipid-reconstituted respiratory type II NADH dehydrogenase activity obtained by compound library screening

    OpenAIRE

    Dunn, Elyse A.; Cook, Gregory M.; Adam Heikal

    2015-01-01

    The energy-generating membrane protein NADH dehydrogenase (NDH-2), a proposed antibacterial drug target (see “Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs” Weinstein et al. 2005 [1]), was screened for modulators of activity in either detergent-solublised or lipid reconstituted (proteolipsome) form. Here we present an annotated list of compounds identified in a small-scale screen against NDH-2. The dataset contains information regarding the li...

  14. In Vitro Activity of Copper(II) Complexes, Loaded or Unloaded into a Nanostructured Lipid System, against Mycobacterium tuberculosis

    Science.gov (United States)

    da Silva, Patricia B.; de Souza, Paula C.; Calixto, Giovana Maria Fioramonti; Lopes, Erica de O.; Frem, Regina C. G.; Netto, Adelino V. G.; Mauro, Antonio E.; Pavan, Fernando R.; Chorilli, Marlus

    2016-01-01

    Tuberculosis (TB) is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis (Mtb), presenting 9.5 million new cases and 1.5 million deaths in 2014. The aim of this study was to evaluate a nanostructured lipid system (NLS) composed of 10% phase oil (cholesterol), 10% surfactant (soy phosphatidylcholine, sodium oleate), and Eumulgin® HRE 40 ([castor oil polyoxyl-40-hydrogenated] in a proportion of 3:6:8), and an 80% aqueous phase (phosphate buffer pH = 7.4) as a tactic to enhance the in vitro anti-Mtb activity of the copper(II) complexes [CuCl2(INH)2]·H2O (1), [Cu(NCS)2(INH)2]·5H2O (2) and [Cu(NCO)2(INH)2]·4H2O (3). The Cu(II) complex-loaded NLS displayed sizes ranging from 169.5 ± 0.7095 to 211.1 ± 0.8963 nm, polydispersity index (PDI) varying from 0.135 ± 0.0130 to 0.236 ± 0.00100, and zeta potential ranging from −0.00690 ± 0.0896 to −8.43 ± 1.63 mV. Rheological analysis showed that the formulations behave as non-Newtonian fluids of the pseudoplastic and viscoelastic type. Antimycobacterial activities of the free complexes and NLS-loaded complexes against Mtb H37Rv ATCC 27294 were evaluated by the REMA methodology, and the selectivity index (SI) was calculated using the cytotoxicity index (IC50) against Vero (ATCC® CCL-81), J774A.1 (ATCC® TIB-67), and MRC-5 (ATCC® CCL-171) cell lines. The data suggest that the incorporation of the complexes into NLS improved the inhibitory action against Mtb by 52-, 27-, and 4.7-fold and the SI values by 173-, 43-, and 7-fold for the compounds 1, 2 and 3, respectively. The incorporation of the complexes 1, 2 and 3 into the NLS also resulted in a significant decrease of toxicity towards an alternative model (Artemia salina L.). These findings suggest that the NLS may be considered as a platform for incorporation of metallic complexes aimed at the treatment of TB. PMID:27196901

  15. Plant P4-ATPases: lipid translocators with a role in membrane traficking

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura

    recently completed the biochemical characterization of two ALA proteins: ALA2, a prevacuolar compartment-localized protein with an unusually tight specificity, and ALA10, a plasma membrane-localized protein with and unforeseen broad substrate specificity. Besides providing an insight into the mechanism...... of lipid translocation, our results suggest that the different transport features of these proteins might be related to their physiological function at the membrane where they are located....... a large family of membrane proteins involved in pumping different physiologically-relevant substrates across biological membranes [4]. The members of the P4 subfamily (also known as flippases) catalyze the energy-driven translocation of lipids necessary for establishing transbilayer lipid asymmetry [5...

  16. Dentate gyrus-cornu ammonis (CA) 4 volume is decreased and associated with depressive episodes and lipid peroxidation in bipolar II disorder: Longitudinal and cross-sectional analyses.

    Science.gov (United States)

    Elvsåshagen, Torbjørn; Zuzarte, Pedro; Westlye, Lars T; Bøen, Erlend; Josefsen, Dag; Boye, Birgitte; Hol, Per K; Malt, Ulrik F; Young, L Trevor; Andreazza, Ana C

    2016-12-01

    Reduced dentate gyrus volume and increased oxidative stress have emerged as potential pathophysiological mechanisms in bipolar disorder. However, the relationship between dentate gyrus volume and peripheral oxidative stress markers remains unknown. Here, we examined dentate gyrus-cornu ammonis (CA) 4 volume longitudinally in patients with bipolar II disorder (BD-II) and healthy controls and investigated whether BD-II is associated with elevated peripheral levels of oxidative stress. We acquired high-resolution structural 3T-magnetic resonance imaging (MRI) images and quantified hippocampal subfield volumes using an automated segmentation algorithm in individuals with BD-II (n=29) and controls (n=33). The participants were scanned twice, at study inclusion and on average 2.4 years later. In addition, we measured peripheral levels of two lipid peroxidation markers (4-hydroxy-2-nonenal [4-HNE] and lipid hydroperoxides [LPH]). First, we demonstrated that the automated hippocampal subfield segmentation technique employed in this work reliably measured dentate gyrus-CA4 volume. Second, we found a decreased left dentate gyrus-CA4 volume in patients and that a larger number of depressive episodes between T1 and T2 predicted greater volume decline. Finally, we showed that 4-HNE was elevated in BD-II and that 4-HNE was negatively associated with left and right dentate gyrus-CA4 volumes in patients. These results are consistent with a role for the dentate gyrus in the pathophysiology of bipolar disorder and suggest that depressive episodes and elevated oxidative stress might contribute to hippocampal volume decreases. In addition, these findings provide further support for the hypothesis that peripheral lipid peroxidation markers may reflect brain alterations in bipolar disorders. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Apolipoprotein C-II and lipoprotein lipase show a temporal and geographic correlation with surfactant lipid synthesis in preparation for birth

    Directory of Open Access Journals (Sweden)

    Gérard-Hudon Marie-Christine

    2010-11-01

    Full Text Available Abstract Background Fatty acids are precursors in the synthesis of surfactant phospholipids. Recently, we showed expression of apolipoprotein C-II (apoC-II, the essential cofactor of lipoprotein lipase (LPL, in the fetal mouse lung and found the protein on the day of the surge of surfactant synthesis (gestation day 17.5 in secretory granule-like structures in the distal epithelium. In the present study, we will answer the following questions: Does apoC-II protein localization change according to the stage of lung development, thus according to the need in surfactant? Are LPL molecules translocated to the luminal surface of capillaries? Do the sites of apoC-II and LPL gene expression change according to the stage of lung development and to protein localization? Results The present study investigated whether the sites of apoC-II and LPL mRNA and protein accumulation are regulated in the mouse lung between gestation day 15 and postnatal day 10. The major sites of apoC-II and LPL gene expression changed over time and were found mainly in the distal epithelium at the end of gestation but not after birth. Accumulation of apoC-II in secretory granule-like structures was not systematically observed, but was found in the distal epithelium only at the end of gestation and soon after birth, mainly in epithelia with no or small lumina. A noticeable increase in surfactant lipid content was measured before the end of gestation day 18, which correlates temporally with the presence of apoC-II in secretory granules in distal epithelium with no or small lumina but not with large lumina. LPL was detected in capillaries at all the developmental times studied. Conclusions This study demonstrates that apoC-II and LPL mRNAs correlate temporally and geographically with surfactant lipid synthesis in preparation for birth and suggests that fatty acid recruitment from the circulation by apoC-II-activated LPL is regionally modulated by apoC-II secretion. We propose a model

  18. Comparative Evaluation of the Lipid Profile in the Serum of Patients with Type II Diabetes Mellitus and Healthy Individuals with Periodontitis.

    Science.gov (United States)

    Thomas, Biju; Prasad, Rajendra B; Shetty, Sucheta; Vishakh, R

    2017-01-01

    Periodontal disease is an immuno-inflammatory disease that is initiated by the interaction between microbial plaque and the periodontal tissues. The data available on the association of periodontal diseases with the lipid profile are conflicting. Therefore, a need for a study in this area was felt. To evaluate the lipid profile in the serum of patients with chronic periodontitis and chronic periodontitis with Type II diabetes mellitus (DM) patients and to compare it with healthy controls, to see whether they can serve as potential markers for chronic periodontitis and also to assess whether periodontitis can have systemic effects. This study is a cross-sectional study. This cross-sectional study was conducted involving 300 participants in the age group of 30-60 years from October 2010 to May 2015. Five milliliters of venous blood was collected from each of the study participants, from the antecubital vein. Lipid profile was assessed using the ERBA commercially available kit. Statistical analysis was carried out using SPSS software version 17. Multigroup comparison was carried out using ANOVA. The honest significant difference Tukey's test was used in conjunction with ANOVA to find means which are significantly different from each other. When the lipid profile was estimated, total cholesterol (TC) levels were seen to be significantly higher (P periodontitis group. High-density lipoprotein (HDL) levels were seen to be significantly higher (P periodontitis group. The triglyceride (TGL) values were also significantly higher (P periodontitis group. The HDL and LDL levels were seen to be nonsignificant between chronic periodontitis and chronic periodontitis with diabetic group. The findings of the study showed that the lipid profile was significantly altered in patients with chronic periodontitis as compared to healthy controls. There was a potentiated difference in the values for TC, VLDL cholesterol, and TGL in patients with chronic periodontitis when compared to

  19. Effect of intensive versus moderate lipid lowering on endothelial function and vascular responsiveness to angiotensin II in stable coronary artery disease.

    Science.gov (United States)

    van der Harst, Pim; Wagenaar, Lodewijk J; Buikema, Hendrik; Voors, Adriaan A; Plokker, H W Thijs; Morshuis, Wim J; Six, A Jacob; Boonstra, Piet W; Nickenig, Georg; Wassmann, Sven; van Veldhuisen, Dirk J; van Gilst, Wiek H

    2005-11-15

    Recent evidence has demonstrated that intensive lipid-lowering therapy with a high-dose statin provides significant clinical benefit beyond moderate lipid-lowering therapy. However, dose-dependent effects of short-term statin therapy on vascular function have not been demonstrated. We studied endothelial function and vascular responsiveness to angiotensin II in patients who had coronary artery diseased and were randomized to receive low- or high-dose atorvastatin (10 or 80 mg, respectively) or placebo. Internal thoracic artery segments were obtained during coronary bypass surgery and studied in vitro. Endothelium-dependent vasodilation was increased with atorvastatin therapy (p = 0.035) but was significantly increased further in patients who received 80 mg compared with those who received 10 mg of atorvastatin (p = 0.05). Endothelium improvement was accompanied by decreased vascular response to angiotensin II (p = 0.039). These findings suggest a mechanism for the clinical benefit of intensive lipid-lowering treatment in coronary heart disease.

  20. 30-year trends in serum lipids among United States adults: results from the National Health and Nutrition Examination Surveys II, III, and 1999-2006.

    Science.gov (United States)

    Cohen, Jerome D; Cziraky, Mark J; Cai, Qian; Wallace, Anna; Wasser, Thomas; Crouse, John R; Jacobson, Terry A

    2010-10-01

    Data from National Health and Nutrition Examination Survey (NHANES) II (1976 to 1980), NHANES III (1988 to 1994), and NHANES 1999 to 2006 were examined to assess trends in total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglycerides (TGs), lipid-lowering medication use, and obesity. Age-adjusted decreases in TC (210 to 200 mg/dl) and LDL cholesterol (134 to 119 mg/dl) were observed. Those with high TC showed a decrease of 9% from NHANES II to NHANES 1999 to 2006, whereas those with LDL cholesterol ≥160 mg/dl showed a decrease of 8%. A significant increase in mean high-density lipoprotein cholesterol was observed (50 to 53 mg/dl, p lipid medication use by those with high cholesterol increased from 16% to 38%. Mean body mass index increased from 26 to 29 kg/m(2), and prevalence of obesity doubled and was significantly associated with increased TG. In conclusion, recent favorable trends in TC and LDL cholesterol are likely due to increased awareness of high cholesterol and the greater use of lipid-lowering drugs. However, countertrends in obesity and TG levels, if continued, will likely have a negative impact on cardiovascular disease in the future.

  1. Part I: In-situ fluorometric quantification of microalgal neutral lipids. Part II: Thermal degradation behavior of investment casting polymer patterns

    Science.gov (United States)

    Zhao, Hongfang

    Research described in this dissertation covers two topics. Part-I is focused on in-situ determination of neutral lipid content of microalgae using a lipophilic fluorescent dye. The traditional Nile red stain-based method for detecting microalgal intracellular lipids is limited due to varying composition and thickness of rigid cell walls. In this study, the addition of dilute acid and heating of solution, were found to greatly enhance staining efficiency of Nile red for microalgal species evaluated. Oil-in-water (O/W) microemulsion stabilized by a non-ionic surfactant was employed as a pseudo-standard that mimics lipid-bearing microalgal cells suspended in water. The average neutral lipid contents determined were very close to the results obtained by traditional gravimetric method and solid phase extraction. Part II of the dissertation explores thermo-physico-chemical properties of polymeric pattern materials, including expanded polystyrene (EPS) foam, polyurethane foam, and epoxy stereolithography (SLA) patterns, that are used in investment casting. Density, elastic modulus, expansion coefficient, thermal degradation behavior, etc. were experimentally investigated for their effects on metal casting quality. The reduction in toxic hydrogen cyanide (HCN) generated during thermal decomposition of polyurethane pattern was achieved by increasing either oxidant level or residence time in heated zone. Thermal degradation kinetics of the pattern materials were examined with a thermogravimetric analysis and activation energies were determined by Kissinger and Flynn-Wall-Ozawa methods.

  2. Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3: understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations.

    Science.gov (United States)

    Williams, Hywel D; Sassene, Philip; Kleberg, Karen; Calderone, Marilyn; Igonin, Annabel; Jule, Eduardo; Vertommen, Jan; Blundell, Ross; Benameur, Hassan; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H

    2013-12-01

    Recent studies have shown that digestion of lipid-based formulations (LBFs) can stimulate both supersaturation and precipitation. The current study has evaluated the drug, formulation and dose-dependence of the supersaturation - precipitation balance for a range of LBFs. Type I, II, IIIA/B LBFs containing medium-chain (MC) or long-chain (LC) lipids, and lipid-free Type IV LBF incorporating different doses of fenofibrate or tolfenamic acid were digested in vitro in a simulated intestinal medium. The degree of supersaturation was assessed through comparison of drug concentrations in aqueous digestion phases (APDIGEST) during LBF digestion and the equilibrium drug solubility in the same phases. Increasing fenofibrate or tolfenamic acid drug loads (i.e., dose) had negligible effects on LC LBF performance during digestion, but promoted drug crystallization (confirmed by XRPD) from MC and Type IV LBF. Drug crystallization was only evident in instances when the calculated maximum supersaturation ratio (SR(M)) was >3. This threshold SR(M) value was remarkably consistent across all LBF and was also consistent with previous studies with danazol. The maximum supersaturation ratio (SR(M)) provides an indication of the supersaturation 'pressure' exerted by formulation digestion and is strongly predictive of the likelihood of drug precipitation in vitro. This may also prove effective in discriminating the in vivo performance of LBFs.

  3. Annotated compound data for modulators of detergent-solubilised or lipid-reconstituted respiratory type II NADH dehydrogenase activity obtained by compound library screening.

    Science.gov (United States)

    Dunn, Elyse A; Cook, Gregory M; Heikal, Adam

    2016-03-01

    The energy-generating membrane protein NADH dehydrogenase (NDH-2), a proposed antibacterial drug target (see "Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs" Weinstein et al. 2005 [1]), was screened for modulators of activity in either detergent-solublised or lipid reconstituted (proteolipsome) form. Here we present an annotated list of compounds identified in a small-scale screen against NDH-2. The dataset contains information regarding the libraries screened, the identities of hit compounds and the physicochemical properties governing solubility and permeability. The implications of these data for future antibiotic discovery are discussed in our associated report, "Comparison of lipid and detergent enzyme environments for identifying inhibitors of membrane-bound energy-transducing proteins" [2].

  4. Annotated compound data for modulators of detergent-solubilised or lipid-reconstituted respiratory type II NADH dehydrogenase activity obtained by compound library screening

    Directory of Open Access Journals (Sweden)

    Elyse A. Dunn

    2016-03-01

    Full Text Available The energy-generating membrane protein NADH dehydrogenase (NDH-2, a proposed antibacterial drug target (see “Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs” Weinstein et al. 2005 [1], was screened for modulators of activity in either detergent-solublised or lipid reconstituted (proteolipsome form. Here we present an annotated list of compounds identified in a small-scale screen against NDH-2. The dataset contains information regarding the libraries screened, the identities of hit compounds and the physicochemical properties governing solubility and permeability. The implications of these data for future antibiotic discovery are discussed in our associated report, “Comparison of lipid and detergent enzyme environments for identifying inhibitors of membrane-bound energy-transducing proteins” [2].

  5. Perspectives on marine zooplankton lipids

    DEFF Research Database (Denmark)

    Kattner, G.; Hagen, W.; Lee, R.F.

    2007-01-01

    We developed new perspectives to identify important questions and to propose approaches for future research on marine food web lipids. They were related to (i) structure and function of lipids, (ii) lipid changes during critical life phases, (iii) trophic marker lipids, and (iv) potential impact ...

  6. Association of Neuropeptide-Y (NPY) and Interleukin-1beta (IL1B), Genotype-Phenotype Correlation and Plasma Lipids with Type-II Diabetes

    OpenAIRE

    Patel, Roma; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Ansarullah; Naresh C. Laddha; Thakker, Ami; A. V. Ramachandran; Begum, Rasheedunnisa

    2016-01-01

    Background Neuropeptide Y (NPY) is known to play a role in the regulation of satiety, energy balance, body weight, and insulin release. Interleukin-1beta (IL1B) has been associated with loss of beta-cell mass in type-II diabetes (TIID). Objectives The present study attempts to investigate the association of NPY exon2 +1128 T/C (Leu7Pro; rs16139), NPY promoter -399 T/C (rs16147) and IL1B -511 C/T (rs16944) polymorphisms with TIID and their correlation with plasma lipid levels, BMI, and IL1B tr...

  7. The Ins and Outs of Lipid Flip-Flop.

    Science.gov (United States)

    Allhusen, John S; Conboy, John C

    2017-01-17

    Our current view of cellular membranes centers on the fluid-mosaic model, which envisions the cellular membrane as a "liquidlike" bilayer of lipids, cholesterol, and proteins that freely diffuse in two dimensions. In stark contrast, the exchange of materials between the leaflets of a bilayer was presumed to be prohibited by the large enthalpic barrier associated with translocating hydrophilic materials, such as a charged lipid headgroup, through the hydrophobic membrane core. This static picture with regard to lipid translocation (or "flip-flop" as it is affectionately known) has been a long-held belief in the study of membrane dynamics. The current accepted membrane model invokes specific protein flippase (inward moving), floppase (outward moving), and scramblase (bidirectional) enzymes that assist in the movement of lipids between the leaflets of cellular membranes. The low rate of protein-free lipid flip-flop has also been a cornerstone of our understanding of the bilateral organization of cellular membrane components, specifically the asymmetric distribution of lipid species found in the luminal and extracellular leaflets of the plasma membrane of eukaryotic cells. Much of the previous work contributing to our current understanding of lipid flip-flop has utilized fluorescent- or spin-labeled lipids. However, there is growing evidence that these lipid probes do not accurately convey the dynamics and thermodynamics of native (unlabeled) lipid motion. This Account summarizes our research efforts directed toward developing a deep physical and chemical understanding of protein-free lipid flip-flop in phospholipid membrane models using sum-frequency vibrational spectroscopy (SFVS). Our use of SFVS enables the direct measurement of native lipid flip-flop in model membranes. In particular, we have explored the kinetic rates and activation thermodynamics of lipid translocation as a means of deciphering the underlying chemical and physical directors governing this

  8. Comparative evaluation of the lipid profile in the serum of patients with type II diabetes mellitus and healthy individuals with periodontitis

    Directory of Open Access Journals (Sweden)

    Biju Thomas

    2017-01-01

    Full Text Available Context: Periodontal disease is an immuno-inflammatory disease that is initiated by the interaction between microbial plaque and the periodontal tissues. The data available on the association of periodontal diseases with the lipid profile are conflicting. Therefore, a need for a study in this area was felt. Aims: To evaluate the lipid profile in the serum of patients with chronic periodontitis and chronic periodontitis with Type II diabetes mellitus (DM patients and to compare it with healthy controls, to see whether they can serve as potential markers for chronic periodontitis and also to assess whether periodontitis can have systemic effects. Settings and Design: This study is a cross-sectional study. Subjects and Methods: This cross-sectional study was conducted involving 300 participants in the age group of 30–60 years from October 2010 to May 2015. Five milliliters of venous blood was collected from each of the study participants, from the antecubital vein. Lipid profile was assessed using the ERBA commercially available kit. Statistical Analysis: Statistical analysis was carried out using SPSS software version 17. Multigroup comparison was carried out using ANOVA. The honest significant difference Tukey's test was used in conjunction with ANOVA to find means which are significantly different from each other. Results: When the lipid profile was estimated, total cholesterol (TC levels were seen to be significantly higher (P < 0.001 in the DM with periodontitis group. High-density lipoprotein (HDL levels were seen to be significantly higher (P < 0.001 in the control group. Mean serum low-density lipoprotein (LDL and very LDL (VLDL levels were seen to be significantly higher (P < 0.001 in the DM with periodontitis group. The triglyceride (TGL values were also significantly higher (P < 0.001 in the DM with periodontitis group. The HDL and LDL levels were seen to be nonsignificant between chronic periodontitis and chronic periodontitis with

  9. Lipids and apolipoproteins A-I, B and C-II and different rapid weight loss programs (weight lifters, wrestlers, boxers and judokas).

    Science.gov (United States)

    Jauhiainen, M; Laitinen, M; Penttilä, I; Nousiainen, U; Ahonen, E

    1985-01-01

    Apolipoproteins A-I, B, C-II and lipids were studied before and after rapid weight loss schedules. The compared groups were all athletic. Apolipoproteins were determined by electroimmunoassay methods using apoproteins purified by chromatofocusing column method. Dextran T10 was shown to increase rocket height in ApoB assay. Over 1% Dextran concentrations gave poor response. The linearity during calibration was from 0.3 to 3.0 g ApoB/l. Baseline values of ApoA-I in wrestlers, weightlifters, boxers and judokas were slightly higher as compared to "normal" population; ApoB was clearly reduced (mean value of 690 mg/l). Weight-loss was significant in each experimental group; mean value of 4.1% in active exercise, sauna and diuretic groups together. Compared as the whole sportsmen group in passive weight loss (or sauna) and diuretic groups the most pronounced changes were seen to be elevated apoprotein concentrations, whereas weight-loss by active rapid exercise resulted no apoprotein changes, but instead an increment in HDL cholesterol and decrement in triglycerides, respectively. The present study was the first to evaluate baseline values of apoproteins A-I, B and C-II in first class athletes and also the possible changes in these and lipid values in rapid weight-loss practices.

  10. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations

    Science.gov (United States)

    Das, Surajit; Kiong Ng, Wai; Tan, Reginald B. H.

    2014-03-01

    This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs.

  11. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers. II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations.

    Science.gov (United States)

    Das, Surajit; Ng, Wai Kiong; Tan, Reginald B H

    2014-03-14

    This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs.

  12. Relationship between insulin resistance and blood lipid and sport in patients with type II diabetes mellitus complicated with hypertension%2型糖尿病合并高血压患者胰岛素低抗

    Institute of Scientific and Technical Information of China (English)

    谭丽艳; 杨红玉; 柴国禄; 沈凌元

    2001-01-01

    Objective To study the relationship between insulin resistance and blood pressure and blood lipid in patients with type II diabetes mellitus complicated with hypertension.Methods The serum concentration of fasting glucose,insulin,lipids and the level of blood pressure were measured in 56 patients with type II diabetes mellitus complicated with hypertension.Results The insulin sensitivity index(ISI) decreased in patients with type II diabetes mellitus complicated with hypertension compared with the patients with type II diabetes mellitus with normal blood pressure(P< 0.05).A negative correlation with hypertension was found between ISI and SBP,DBP,TG,ApoB in patients with type II diabetes mellitus complicated with hypertension(P<0.05).There was a positive correlation between ISI and HDL in patients with type II diabetes mellitus complicated with hypertension(P<0.05).Conclusion Insulin resistance presents in patients of type II diabetes mellitus complicated with hypertension.Insulin resistance is the major cause of hypertension and lipid metabolic disturbance in patients with type II diabetes mellitus complicated with hypertension.

  13. Perspectives on marine zooplankton lipids

    DEFF Research Database (Denmark)

    Kattner, G.; Hagen, W.; Lee, R.F.

    2007-01-01

    We developed new perspectives to identify important questions and to propose approaches for future research on marine food web lipids. They were related to (i) structure and function of lipids, (ii) lipid changes during critical life phases, (iii) trophic marker lipids, and (iv) potential impact...... of climate change. The first addresses the role of lipids in membranes, storage lipids, and buoyancy with the following key question: How are the properties of membranes and deposits affected by the various types of lipids? The second deals with the importance of various types of lipids during reproduction......, development, and resting phases and addresses the role of the different storage lipids during growth and dormancy. The third relates to trophic marker lipids, which are an important tool to follow lipid and energy transfer through the food web. The central question is how can fatty acids be used to identify...

  14. Montelukast-loaded nanostructured lipid carriers: part II pulmonary drug delivery and in vitro-in vivo aerosol performance.

    Science.gov (United States)

    Patil-Gadhe, Arpana; Kyadarkunte, Abhay; Patole, Milind; Pokharkar, Varsha

    2014-09-01

    The aim of the present study was to establish the potential of montelukast loaded nanostructured lipid carrier (MNLC) for pulmonary application. The formulated nanoparticles were evaluated in vitro for aerodynamic characterization and in vivo for pulmokinetics in Wistar rats. The in vitro cytotoxicity was performed on A549 cell line and compared with montelukast-aqueous solution. MNLC was prepared with montelukast (0.2%), Precirol ATO5 (solid lipid), and Capryol-90 (liquid lipid) in the ratio of 7:3 using melt-emulsification-homogenization method. dl-Pyrrolidonecarboxylic acid salt of l-cocyl arginine ethyl ester (CAE), a biodegradable surfactant in the concentration of 1% was used to stabilize the nanoparticles. The particle size and encapsulation efficiency (EE) were 184.6 ± 2.7 nm and >95%, respectively. MNLC-Dry powder for inhalation (DPI) was prepared by lyophilization using 3% mannitol as cryoprotectant and carrier. MNLC-DPI was evaluated for flow, crystallographic and thermal properties. Mass median diameters (MMD) and density for MNLC-DPI were found to be 15.1 ± 1.4 μm and 0.051 ± 0.002 g/cc, respectively. In vitro aerosol performance study indicated more than 95% of the emitted dose (ED) at both the flow rates studied. Mass median aerodynamic diameters (MMAD) of 3.24 ± 0.67 μm with 69.98 ± 1.9% fine particle fraction (FPF) were obtained at 30 L/min flow rate, whereas at 60 L/min MMAD and FPF were found to be 2.83 ± 0.46 μm and 90.22 ± 2.6%, respectively. In vitro cytotoxicity study on A549 cells revealed higher safety of MNLC than pure drug. The pulmonary pharmacokinetic study demonstrated improved bioavailability, longer residence of drug in the lung and targeting factor of 11.76 for MNLC as compared to montelukast-aqueous solution. Thus, the results of the study demonstrated the potential of montelukast lipidic nanoparticulate formulation to improve the efficacy with reduced toxicity leading to better performance of drug as MNLC-DPI for

  15. Association of Neuropeptide-Y (NPY) and Interleukin-1beta (IL1B), Genotype-Phenotype Correlation and Plasma Lipids with Type-II Diabetes

    Science.gov (United States)

    Mansuri, Mohmmad Shoab; Ansarullah; Laddha, Naresh C.; Thakker, Ami; Ramachandran, A. V.; Begum, Rasheedunnisa

    2016-01-01

    Background Neuropeptide Y (NPY) is known to play a role in the regulation of satiety, energy balance, body weight, and insulin release. Interleukin-1beta (IL1B) has been associated with loss of beta-cell mass in type-II diabetes (TIID). Objectives The present study attempts to investigate the association of NPY exon2 +1128 T/C (Leu7Pro; rs16139), NPY promoter -399 T/C (rs16147) and IL1B -511 C/T (rs16944) polymorphisms with TIID and their correlation with plasma lipid levels, BMI, and IL1B transcript levels. Methods PCR-RFLP was used for genotyping these polymorphisms in a case-control study involving 558 TIID patients and 1085 healthy age-matched controls from Gujarat. Linkage disequilibrium and haplotype analysis of the NPY polymorphic sites were performed to assess their association with TIID. IL1B transcript levels in PBMCs were also assessed in 108 controls and 101 patients using real-time PCR. Results Our results show significant association of both structural and promoter polymorphisms of NPY (pLDL levels (p = 0.01). Conclusion The present study provides an evidence for a strong correlation between structural and promoter polymorphisms of NPY gene and upregulation of IL1B transcript levels with susceptibility to TIID and altering the lipid metabolism in Gujarat population. PMID:27749914

  16. Effects of Low-Molecular-Weight Fucoidan and High Stability Fucoxanthin on Glucose Homeostasis, Lipid Metabolism, and Liver Function in a Mouse Model of Type II Diabetes

    Directory of Open Access Journals (Sweden)

    Hong-Ting Victor Lin

    2017-04-01

    Full Text Available The combined effects of low-molecular-weight fucoidan (LMF and fucoxanthin (Fx in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism. As for glucose and lipid metabolism in the adipose tissue, the expression of insulin receptor substrate (IRS-1, glucose transporter (GLUT, peroxisome proliferator-activated receptor gamma (PPARγ, and uncoupling protein (UCP-1 mRNAs in the adipose tissue of diabetic mice was significantly upregulated by Fx and LMF + Fx, and levels of inflammatory adipocytokines, such as adiponectin, tumor necrosis factor-α (TNF-α, and interleukin-6 (IL-6, were significantly modulated only by LMF + Fx supplementation. The efficacy of LMF + Fx supplementation on the decrease in urinary sugar and on glucose and lipid metabolism in the white adipose tissue of db/db mice was better than that of Fx or LMF alone, indicating the occurrence of a synergistic effect of LMF and Fx.

  17. The role of lipid-based nano delivery systems on oral bioavailability enhancement of fenofibrate, a BCS II drug: comparison with fast-release formulations.

    Science.gov (United States)

    Weng, Tengfei; Qi, Jianping; Lu, Yi; Wang, Kai; Tian, Zhiqiang; Hu, Kaili; Yin, Zongning; Wu, Wei

    2014-09-24

    The aim of this study was to compare various formulations solid dispersion pellets (SDP), nanostructured lipid carriers (NLCs) and a self-microemulsifying drug delivery system (SMEDDS) generally accepted to be the most efficient drug delivery systems for BCS II drugs using fenofibrate (FNB) as a model drug. The size and morphology of NLCs and SMEDDS was characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Their release behaviors were investigated in medium with or without pancreatic lipase. The oral bioavailability of the various formulations was compared in beagle dogs using commercial Lipanthyl® capsules (micronized formulation) as a reference. The release of FNB from SDP was much faster than that from NLCs and SMEDDS in medium without lipase, whereas the release rate from NLCs and SMEDDS was increased after adding pancreatic lipase into the release medium. However, NLCs and SMEDDS increased the bioavailability of FNB to 705.11% and 809.10%, respectively, in comparison with Lipanthyl® capsules, although the relative bioavailability of FNB was only 366.05% after administration of SDPs. Thus, lipid-based drug delivery systems (such as NLCs and SMEDDS) may have more advantages than immediate release systems (such as SDPs and Lipanthyl® capsules).

  18. CORRELATION OF PLASMA FIBRINOGEN WITH BLOOD PRESSURE, BMI, LIPID PROFILE AND GLYCEMIC STATUS IN TYPE II D M

    Directory of Open Access Journals (Sweden)

    Suresh

    2014-12-01

    Full Text Available BACKGROUND: Diabetes is the most common metabolic disorder all over the world3.The incidence of diabetes is showing an alarming rise in developing countries, particularly in India. Type 2 diabetes is the most prevalent form in India and constitutes more than 95% of the cases.9 During the past decade, the potential role of haemostatic factors particularly fibrinogen in various disorders and their complication has gained considerable interest. Plasma fibrinogen is a important marker in type 2 Diabetes, but its correlation with smoking, age, sex, hypertension, obesity, family history lipids, has not been evaluated in large studies. In view of paucity of data from Indian studies, we attempt to correlate plasma fibrinogen with blood pressure, BMI, lipid profile and glycemic status in type 2 diabetes mellitus. METHODS: A total of 100, known and newly detected type-2 diabetic patients with and without associated hypertension of more than 40 years of age belonging to both sexes were included. All these patients were registered cases in Basaveshwar Teaching & General Hospital, Gulbarga as outpatients and in-patients. Type-2 diabetic patients associated with myocardial infarction, stroke, chronic inflammatory diseases, tuberculosis, malignancy, secondary hypertension and pregnancy were excluded from this study. After a detailed clinical examination, the following investigations were done: For diabetes mellitus: Random blood sugar, fasting blood sugar, post-prandial blood sugar and glycosylated haemoglobin (ERBA Kit. Renal profile: Blood urea and serum creatinine. Serum lipids: Cholesterol, triglyceride (TG, high density lipoprotein (HDL and low density lipoprotein (LDL by commercially available kits (ERBA Kit. Routine urine examination: Sugar and albumin. Estimation of plasma fibrinogen: The plasma fibrinogen was estimated by thrombin-clotting method by using FIBROQUANT KIT [Tulip Diagnostics (P Ltd.]. OBJECTIVES: To know the fibrinogen levels in patients

  19. Cyanobacterial photosystem II at 2.9-A resolution and the role of quinones, lipids, channels and chloride

    NARCIS (Netherlands)

    Guskov, Albert; Kern, Jan; Gabdulkhakov, Azat; Broser, Matthias; Zouni, Athina; Saenger, Wolfram

    2009-01-01

    Photosystem II (PSII) is a large homodimeric protein-cofactor complex located in the photosynthetic thylakoid membrane that acts as light-driven water:plastoquinone oxidoreductase. The crystal structure of PSII from Thermosynechococcus elongatus at 2.9-A resolution allowed the unambiguous assignment

  20. Study of biodistribution of lipidic nanospheres charged with cis-diaminedichloroplatinum (II) and labelled with radioactive nuclei of Indium-111; Estudio de biodistribucion de nanoesferas lipidicas cargadas con cis-diaminodicloroplatino (II) y marcadas con nucleos radioactivos de Indio-111

    Energy Technology Data Exchange (ETDEWEB)

    Lopez R, V.; Juarez O, C.; Medina L, A. [Unidad de Investigacion Biomedica en Cancer INCAN-UNAM, Mexico D.F. (Mexico); Perez C, E.; Garcia L, P. [Instituto nacional de cancerologia, Mexico D.F. (Mexico)

    2007-07-01

    The general objective of the study was to evaluate the lipidic nanospheres biodistribution charged with cis-diaminedichloroplatinum (II) (cis-DDP) and labelled with radioactive nuclei of Indium-111 (Lip-Cis-in-111) in Wistar rats and in a tumoral model of CaCu. The conclusions were: 1. The system Lip-Cis-in-111 it presents a very fast elimination probably, to a fast recognition response of the reticuloendothelial system (RES). 2. It is planned to make modifications to the formulation to increase the quantity of the hydrophilic polymer (PEG), so that its time of residence in the blood is bigger and allow a bigger accumulation in the tumor. (Author)

  1. Lipid Profile

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Lipid Profile Share this page: Was this page helpful? Also ... as: Lipid Panel; Coronary Risk Panel Formal name: Lipid Profile Related tests: Cholesterol ; HDL Cholesterol ; LDL Cholesterol ; Triglycerides ; ...

  2. Differences between easy- and difficult-to-mill chickpea (Cicer arietinum L.) genotypes. Part II: protein, lipid and mineral composition.

    Science.gov (United States)

    Wood, Jennifer A; Knights, Edmund J; Campbell, Grant M; Choct, Mingan

    2014-05-01

    Part I introduced the concept of easy- and difficult-to-mill chickpea genotypes, the broad chemical composition of their seed fractions and proposed mechanistic explanations for physical differences consistent with observed variation in milling ease. Part II continues this research by delving deeper into the amino acid, fatty acid and mineral components. No association between fatty acid composition and ease of milling was observed. However, particular amino acids and mineral elements were identified that further support roles of lectins, pectins and mineral-facilitated binding in the adhesion of chickpea seed coat and cotyledons. These differences suggest underlying mechanisms that could be exploited by breeding programmes to improve milling performance. This study shows that the content and composition of amino acids, fatty acids and minerals within different chickpea tissues vary with seed type (desi and kabuli) and within desi genotypes in ways that are consistent with physical explanations of how seed structure and properties relate to milling behaviour. © 2013 Society of Chemical Industry.

  3. EFFECTS OF TRAINING AND DETRAINING ON GLYCOSYLATED HAEMOGLOBIN, GLYCAEMIA AND LIPID PROFILE IN TYPE-II DIABETICS.

    Science.gov (United States)

    Yuing Farias, Tuillang; Santos-Lozano, Alejandro; Solís Urra, Patricio; Cristi-Montero, Carlos

    2015-10-01

    Objetivo: el propósito del presente estudio fue determinar el efecto del entrenamiento y las consecuencias del desentrenamiento comparando un protocolo de entrenamiento aeróbico (E-Aer) y otro de sobrecarga (E-Sob). Métodos: participaron 30 personas entre 45-50 años de edad con diagnóstico de diabetes mellitus tipo II (DMII) sin tratamiento farmacológico. Fueron aleatorizados a un grupo de E-Aer (65% de su esfuerzo máximo) o a un grupo de E-Sob (protocolo 1 x 2 x 3 al 65% de 1RM). Se midió el peso, el índice de masa corporal, el colesterol total, HDL-C, LDL-C, triglicéridos, glucemia en ayuno y la hemoglobina glucosilada (HbA1C) al inicio, al finalizar las seis semanas de entrenamiento y tras seis semanas de desentrenamiento. Resultados: los resultados indican que ambos protocolos de entrenamiento físico son capaces de inducir modificaciones significativas en el perfil lipídico, la glicemia en ayuno y los niveles de HbA1C; sin embargo, solo el grupo E-Sob demostró mantener los beneficios logrados tras haber interrumpido el programa de entrenamiento en la reducción del LDL-C, HbA1C y en el incremento del HDL-C. Conclusiones: el ejercicio de sobrecarga en personas con DMII influye de manera importante en la salud, efecto que podría mantenerse incluso si se llega a interrumpir a corto plazo el programa de entrenamiento.

  4. The membranotropic activity of N-terminal peptides from the pore-forming proteins sticholysin I and II is modulated by hydrophobic and electrostatic interactions as well as lipid composition

    Indian Academy of Sciences (India)

    Uris Ros; Lohans Pedrera; Daylín Díaz; Juan C De Karam; Tatiane P Sudbrack; Pedro A Valiente; Diana Martínez; Eduardo M Cilli; Fabiola Pazos; Rosangela Itri; Maria E Lanio; Shirley Schreier; Carlos Álvarez

    2011-12-01

    The sea anemone Stichodactyla helianthus produces two pore-forming proteins, sticholysins I and II (St I and St II). Despite their high identity (93%), these toxins exhibit differences in hemolytic activity that can be related to those found in their N-terminal. To clarify the contribution of the N-terminal amino acid residues to the activity of the toxins, we synthesized peptides spanning residues 1–31 of St I (StI1-31) or 1–30 of St II (StII1-30) and demonstrated that StII1-30 promotes erythrocyte lysis to a higher extent than StI1-31. For a better understanding of the molecular mechanism underlying the peptide activity, here we studied their binding to lipid monolayers and pemeabilizing activity in liposomes. For this, we examined the effect on peptide membranotropic activity of including phospatidic acid and cholesterol in a lipid mixture of phosphatidylcholine and sphingomyelin. The results suggest the importance of continuity of the 1–10 hydrophobic sequence in StII1-30 for displaying higher binding and activity, in spite of both peptides’ abilities to form pores in giant unilamellar vesicles. Thus, the different peptide membranotropic action is explained in terms of the differences in hydrophobic and electrostatic peptide properties as well as the enhancing role of membrane inhomogeneities.

  5. Association of Neuropeptide-Y (NPY) and Interleukin-1beta (IL1B), Genotype-Phenotype Correlation and Plasma Lipids with Type-II Diabetes.

    Science.gov (United States)

    Patel, Roma; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Ansarullah; Laddha, Naresh C; Thakker, Ami; Ramachandran, A V; Begum, Rasheedunnisa

    2016-01-01

    Neuropeptide Y (NPY) is known to play a role in the regulation of satiety, energy balance, body weight, and insulin release. Interleukin-1beta (IL1B) has been associated with loss of beta-cell mass in type-II diabetes (TIID). The present study attempts to investigate the association of NPY exon2 +1128 T/C (Leu7Pro; rs16139), NPY promoter -399 T/C (rs16147) and IL1B -511 C/T (rs16944) polymorphisms with TIID and their correlation with plasma lipid levels, BMI, and IL1B transcript levels. PCR-RFLP was used for genotyping these polymorphisms in a case-control study involving 558 TIID patients and 1085 healthy age-matched controls from Gujarat. Linkage disequilibrium and haplotype analysis of the NPY polymorphic sites were performed to assess their association with TIID. IL1B transcript levels in PBMCs were also assessed in 108 controls and 101 patients using real-time PCR. Our results show significant association of both structural and promoter polymorphisms of NPY (p<0.0001 and p<0.0001 respectively) in patients with TIID. However, the IL1B C/T polymorphism did not show any association (p = 0.3797) with TIID patients. Haplotype analysis revealed more frequent association of CC and CT haplotypes (p = 3.34 x 10-5, p = 6.04 x 10-9) in diabetics compared to controls and increased the risk of diabetes by 3.02 and 2.088 respectively. Transcript levels of IL1B were significantly higher (p<0.0001) in patients as compared to controls. Genotype-phenotype correlation of IL1B polymorphism did not show any association with its higher transcript levels. In addition, NPY +1128 T/C polymorphism was found to be associated with increased plasma LDL levels (p = 0.01). The present study provides an evidence for a strong correlation between structural and promoter polymorphisms of NPY gene and upregulation of IL1B transcript levels with susceptibility to TIID and altering the lipid metabolism in Gujarat population.

  6. Phospholipid flippases Lem3p-Dnf1p and Lem3p-Dnf2p are involved in the sorting of the tryptophan permease Tat2p in yeast.

    Science.gov (United States)

    Hachiro, Takeru; Yamamoto, Takaharu; Nakano, Kenji; Tanaka, Kazuma

    2013-02-01

    The type 4 P-type ATPases are flippases that generate phospholipid asymmetry in membranes. In budding yeast, heteromeric flippases, including Lem3p-Dnf1p and Lem3p-Dnf2p, translocate phospholipids to the cytoplasmic leaflet of membranes. Here, we report that Lem3p-Dnf1/2p are involved in transport of the tryptophan permease Tat2p to the plasma membrane. The lem3Δ mutant exhibited a tryptophan requirement due to the mislocalization of Tat2p to intracellular membranes. Tat2p was relocalized to the plasma membrane when trans-Golgi network (TGN)-to-endosome transport was inhibited. Inhibition of ubiquitination by mutations in ubiquitination machinery also rerouted Tat2p to the plasma membrane. Lem3p-Dnf1/2p are localized to endosomal/TGN membranes in addition to the plasma membrane. Endocytosis mutants, in which Lem3p-Dnf1/2p are sequestered to the plasma membrane, also exhibited the ubiquitination-dependent missorting of Tat2p. These results suggest that Tat2p is ubiquitinated at the TGN and missorted to the vacuolar pathway in the lem3Δ mutant. The NH(2)-terminal cytoplasmic region of Tat2p containing ubiquitination acceptor lysines interacted with liposomes containing acidic phospholipids, including phosphatidylserine. This interaction was abrogated by alanine substitution mutations in the basic amino acids downstream of the ubiquitination sites. Interestingly, a mutant Tat2p containing these substitutions was missorted in a ubiquitination-dependent manner. We propose the following model based on these results; Tat2p is not ubiquitinated when the NH(2)-terminal region is bound to membrane phospholipids, but if it dissociates from the membrane due to a low level of phosphatidylserine caused by perturbation of phospholipid asymmetry in the lem3Δ mutant, Tat2p is ubiquitinated and then transported from the TGN to the vacuole.

  7. The Crystal Structure of the Lipid II-degrading Bacteriocin Syringacin M Suggests Unexpected Evolutionary Relationships between Colicin M-like Bacteriocins

    Science.gov (United States)

    Grinter, Rhys; Roszak, Aleksander W.; Cogdell, Richard J.; Milner, Joel J.; Walker, Daniel

    2012-01-01

    Colicin-like bacteriocins show potential as next generation antibiotics with clinical and agricultural applications. Key to these potential applications is their high potency and species specificity that enables a single pathogenic species to be targeted with minimal disturbance of the wider microbial community. Here we present the structure and function of the colicin M-like bacteriocin, syringacin M from Pseudomonas syringae pv. tomato DC3000. Syringacin M kills susceptible cells through a highly specific phosphatase activity that targets lipid II, ultimately inhibiting peptidoglycan synthesis. Comparison of the structures of syringacin M and colicin M reveals that, in addition to the expected similarity between the homologous C-terminal catalytic domains, the receptor binding domains of these proteins, which share no discernible sequence homology, share a striking structural similarity. This indicates that the generation of the novel receptor binding and species specificities of these bacteriocins has been driven by diversifying selection rather than diversifying recombination as suggested previously. Additionally, the structure of syringacin M reveals the presence of an active site calcium ion that is coordinated by a conserved aspartic acid side chain and is essential for catalytic activity. We show that mutation of this residue to alanine inactivates syringacin M and that the metal ion is absent from the structure of the mutant protein. Consistent with the presence of Ca2+ in the active site, we show that syringacin M activity is supported by Ca2+, along with Mg2+ and Mn2+, and the protein is catalytically inactive in the absence of these ions. PMID:22995910

  8. Association of PvuII and XbaI polymorphisms on estrogen receptor alpha (ESR1) gene to changes into serum lipid profile of post-menopausal women: Effects of aging, body mass index and breast cancer incidence.

    Science.gov (United States)

    Gomes-Rochette, Neuza Felix; Souza, Letícia Soncini; Tommasi, Bruno Otoni; Pedrosa, Diego França; Eis, Sérgio Ragi; Fin, Irani do Carmo Francischetto; Vieira, Fernando Luiz Herkenhoff; Graceli, Jones Bernardes; Rangel, Letícia Batista Azevedo; Silva, Ian Victor

    2017-01-01

    Estrogen is a steroidal hormone involved in several physiological functions in the female body including regulation of serum lipid metabolism and breast cancer (BC). Estrogen actions on serum lipids mostly occur through its binding to intracellular Estrogen Receptor alpha (ERalpha) isoform, expressed in most of tissues. This gene (ESR1) exhibit many polymorphic sites (SNPs) located either on translated and non-translated regions that regulate ERalpha protein expression and function. This paper aimed to investigate the association of two intronic SNPs of ESR1 gene, namely c454-397T>C (PvuII) and c454-351A>G (XbaI) to alterations in serum levels of total cholesterol (T-chol), total lipid (TL), low density lipoprotein cholesterol (LDL), high density lipoprotein (HDL), and triglycerides (TG) in a cohort of post-menopausal women. In addition, we aimed to associate presence of these SNPs to development of BC along 5 years period. To do so, a group of healthy 499, highly miscigenated, post-menopausal Brazilian women, were carried using PCR-FRLP technique and further confirmed by automatic sequence analysis as well followed through 5 years for BC incidence. Measurements of serum lipid profile by standard commercial methods were carried individually whereas Dual Energy X-ray Absorciometry (DXA) measured Body Mass Indexes (BMI), Fat Mass (FM), Lean Body Mass (LBM), and Body Water Content (BWC). No effects of PvuII SNP on ESR1 gene were observed on patient´s serum T-chol, TL, LDL, HDL, and TG. However, c454-397T>C PvuII SNP is associated to lower body fat and higher levels of lean mass and body water and lower incidence of BC. On the other hand, statistically significant effect of XbaI c454-351A>G SNP on serum TG and TL levels. Patients homozygous for X allele were followed up from 2010-2015. They showed higher incidence of breast cancer (BC) when compared to either heterozygous and any P allele combination. Moreover, the increasing of TG and TL serum concentrations

  9. Association of PvuII and XbaI polymorphisms on estrogen receptor alpha (ESR1) gene to changes into serum lipid profile of post-menopausal women: Effects of aging, body mass index and breast cancer incidence

    Science.gov (United States)

    Gomes-Rochette, Neuza Felix; Souza, Letícia Soncini; Tommasi, Bruno Otoni; Pedrosa, Diego França; Fin, Irani do Carmo Francischetto; Vieira, Fernando Luiz Herkenhoff; Graceli, Jones Bernardes; Rangel, Letícia Batista Azevedo; Silva, Ian Victor

    2017-01-01

    Estrogen is a steroidal hormone involved in several physiological functions in the female body including regulation of serum lipid metabolism and breast cancer (BC). Estrogen actions on serum lipids mostly occur through its binding to intracellular Estrogen Receptor alpha (ERalpha) isoform, expressed in most of tissues. This gene (ESR1) exhibit many polymorphic sites (SNPs) located either on translated and non-translated regions that regulate ERalpha protein expression and function. This paper aimed to investigate the association of two intronic SNPs of ESR1 gene, namely c454-397T>C (PvuII) and c454-351A>G (XbaI) to alterations in serum levels of total cholesterol (T-chol), total lipid (TL), low density lipoprotein cholesterol (LDL), high density lipoprotein (HDL), and triglycerides (TG) in a cohort of post-menopausal women. In addition, we aimed to associate presence of these SNPs to development of BC along 5 years period. To do so, a group of healthy 499, highly miscigenated, post-menopausal Brazilian women, were carried using PCR-FRLP technique and further confirmed by automatic sequence analysis as well followed through 5 years for BC incidence. Measurements of serum lipid profile by standard commercial methods were carried individually whereas Dual Energy X-ray Absorciometry (DXA) measured Body Mass Indexes (BMI), Fat Mass (FM), Lean Body Mass (LBM), and Body Water Content (BWC). No effects of PvuII SNP on ESR1 gene were observed on patient´s serum T-chol, TL, LDL, HDL, and TG. However, c454-397T>C PvuII SNP is associated to lower body fat and higher levels of lean mass and body water and lower incidence of BC. On the other hand, statistically significant effect of XbaI c454-351A>G SNP on serum TG and TL levels. Patients homozygous for X allele were followed up from 2010–2015. They showed higher incidence of breast cancer (BC) when compared to either heterozygous and any P allele combination. Moreover, the increasing of TG and TL serum concentrations

  10. A putative plant aminophospholipid flippase, the Arabidopsis P4 ATPase ALA1, localizes to the plasma membrane following association with a β-subunit.

    Directory of Open Access Journals (Sweden)

    Rosa L López-Marqués

    Full Text Available Plasma membranes in eukaryotic cells display asymmetric lipid distributions with aminophospholipids concentrated in the inner leaflet and sphingolipids in the outer leaflet. This unequal distribution of lipids between leaflets is, amongst several proposed functions, hypothesized to be a prerequisite for endocytosis. P4 ATPases, belonging to the P-type ATPase superfamily of pumps, are involved in establishing lipid asymmetry across plasma membranes, but P4 ATPases have not been identified in plant plasma membranes. Here we report that the plant P4 ATPase ALA1, which previously has been connected with cold tolerance of Arabidopsis thaliana, is targeted to the plasma membrane and does so following association in the endoplasmic reticulum with an ALIS protein β-subunit.

  11. The relationship between vegetables and fruits intake and glycosylated hemoglobin values, lipids profiles and nitrogen status in type II inactive diabetic patients

    Directory of Open Access Journals (Sweden)

    Marjan Tabesh

    2013-01-01

    Conclusions : Intake of vegetables and fruits may reduce the glycosylated hemoglobin, therefore choosing the appropriate diet with high fruits and vegetables may help to develop antioxidant defense and reduce the HbA1C in diabetic patients but it did not have any impact on lipids profiles, BUN/creatinine and urine protein 24 h.

  12. Lipid somersaults

    DEFF Research Database (Denmark)

    Günther-Pomorski, Thomas; Menon, Anant K.

    2016-01-01

    Membrane lipids diffuse rapidly in the plane of the membrane but their ability to flip spontaneously across a membrane bilayer is hampered by a significant energy barrier. Thus spontaneous flip-flop of polar lipids across membranes is very slow, even though it must occur rapidly to support divers...

  13. G protein-membrane interactions II: Effect of G protein-linked lipids on membrane structure and G protein-membrane interactions.

    Science.gov (United States)

    Casas, Jesús; Ibarguren, Maitane; Álvarez, Rafael; Terés, Silvia; Lladó, Victoria; Piotto, Stefano P; Concilio, Simona; Busquets, Xavier; López, David J; Escribá, Pablo V

    2017-09-01

    G proteins often bear myristoyl, palmitoyl and isoprenyl moieties, which favor their association with the membrane and their accumulation in G Protein Coupled Receptor-rich microdomains. These lipids influence the biophysical properties of membranes and thereby modulate G protein binding to bilayers. In this context, we showed here that geranylgeraniol, but neither myristate nor palmitate, increased the inverted hexagonal (HII) phase propensity of phosphatidylethanolamine-containing membranes. While myristate and palmitate preferentially associated with phosphatidylcholine membranes, geranylgeraniol favored nonlamellar-prone membranes. In addition, Gαi1 monomers had a higher affinity for lamellar phases, while Gβγ and Gαβγ showed a marked preference for nonlamellar prone membranes. Moreover, geranylgeraniol enhanced the binding of G protein dimers and trimers to phosphatidylethanolamine-containing membranes, yet it decreased that of monomers. By contrast, both myristate and palmitate increased the Gαi1 preference for lamellar membranes. Palmitoylation reinforced the binding of the monomer to PC membranes and myristoylation decreased its binding to PE-enriched bilayer. Finally, binding of dimers and trimers to lamellar-prone membranes was decreased by palmitate and myristate, but it was increased in nonlamellar-prone bilayers. These results demonstrate that co/post-translational G protein lipid modifications regulate the membrane lipid structure and that they influence the physico-chemical properties of membranes, which in part explains why G protein subunits sort to different plasma membrane domains. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The impact of auxins used in assisted phytoextraction of metals from the contaminated environment on the alterations caused by lead(II) ions in the organization of model lipid membranes.

    Science.gov (United States)

    Hąc-Wydro, Katarzyna; Sroka, Aleksandra; Jabłońska, Klaudia

    2016-07-01

    Auxins are successfully used to improve phytoextraction efficiency of metal ions from the contaminated environment, however, the mechanism of their activity in this field is not explained. Auxins are known to exert various biochemical alterations in the plant membranes and cells, but their activity involves also direct interactions with lipids leading to changes in membrane organization. Following the suggestion that the auxins-induced modifications in membrane properties alleviate toxic effect of metal ions in this paper we have undertaken the comparative studies on the effect of metal ions and metal ions/auxins mixtures on model membrane systems. The experiments were done on lipid monolayers differing in their composition spread on water subphase and on Pb(2+), Indole-3-acetic acid (IAA), 1-Naphthaleneacetic acid (NAA) and Pb(2+)/IAA and Pb(2+)/NAA water solutions. The analysis of the collected data suggests that metal ions and auxins can change fluidity of the lipid systems and weaken the interactions between monolayer components. This manifested in the increase of the mean area per molecule and the excess area per molecule values for the films on Pb(2+), auxins as well as Pb(2+)/auxin solutions as compared to the values on pure water subphase. However, the presence of auxin in the mixture with lead(II) ions makes the alterations induced by sole metal ions weaker. This effect was more pronounced for the membranes of a higher packing. Thus it was proposed that auxins may enhance phytoextraction of metal ions by weakening their destabilizing effect on membrane. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Effects of lipids and oleic acid on biomass development in anaerobic fixed-bed reactors. Part II: Oleic acid toxicity and biodegradability.

    Science.gov (United States)

    Alves, M M; Vieira, J A; Pereira, R M; Pereira, M A; Mota, M

    2001-01-01

    Oleic acid toxicity and biodegradability were followed during long-term operation of two similar anaerobic fixed-bed units. When treating an oleate based effluent, the sludge from the bioreactor that was acclimated with lipids during the first operation period, showed a higher tolerance to oleic acid toxicity (IC50 = 137 mg/l) compared with the sludge fed with a non-fat substrate (IC50 = 80 mg/l). This sludge showed also the highest biodegradation capacity of oleic acid, achieving maximum methane production rates between 33 and 46 mlCH4(STP)/gVS.day and maximum percentages of methanization between 85 and 98% for the range of concentrations between 500 and 900 mg oleate/l. When oleate was the sole carbon source fed to both digesters, the biomass became encapsulated with organic matter, possibly oleate or an intermediate of its degradation, e.g. stearate that was degraded at a maximum rate of 99 mlCH4(STP)/gVS.day. This suggests the possibility of using adsorption-degradation cycles for the treatment of LCFA based effluents. Both tolerance to toxicity and biodegradability of oleic acid were improved by acclimatization with lipids or oleate below a threshold concentration.

  16. A mathematical model for the study of lipid accumulation in oleaginous microorganisms. II. Study of cellular lipids of Mucor circinelloides during growth on a vegetable oil

    Directory of Open Access Journals (Sweden)

    Aggelis, G.

    1995-10-01

    Full Text Available Microbial oil production from fatty materials of animal or plant origin has been an object of research and industrial interest for many years. During the process of microbial growth/accumulation of fat reserves, the dominating phenomena that define the composition of endocellular fat are, first, the specific process of incorporation of substrate fatty acids into the microbial cell and, second, the endocellular changes of fatty acids defined by the enzymic capabilities of the microorganism. The fatty acids will either be degraded for growth needs or act as substrate of endocellular biotransformation processes, leading to concentration changes and production of "new" fatty acids which did not previously exist in the substrate.
    The purpose of the present work is to study the endocellular lipids of Mucor circinelloidesCBS 172-27 grown on sunflower oil. The mathematical model, described in part I, was applied in order to investigate the following:
    a. Microorganism specificity in the incorporation of substrate fatty acids.
    b. Microorganism specificity in the degradation of fatty acids present in the reserve fat.
    c. Possibilities of endocellular biotransformations during the microbial growth.
    In conclusion, this work is aimed at developing a quantitative expression of parameters defining the lipid composition of fat reserves. The proposed mathematical model can be used not only for selection of microbial strains having specific enzymic potential but also for substrate selection.

    La producción de aceites microbianos a partir de materiales grasos de origen animal o vegetal ha sido objeto de investigación e interés industrial durante muchos años. En el proceso de crecimiento microbiano/acumulación de reservas grasas, los fenómenos dominantes que definen la composición de grasa endocelular son, primero, el proceso específico de incorporación de ácidos grasos como sustratos en la célula microbiana

  17. Synthesis of nisin AB dicarba analogs using ring-closing metathesis: influence of sp(3) versus sp(2) hybridization of the α-carbon atom of residues dehydrobutyrine-2 and dehydroalanine-5 on the lipid II binding affinity.

    Science.gov (United States)

    Slootweg, Jack C; van Herwerden, Eric F; van Doremalen, Mark F M; Breukink, Eefjan; Liskamp, Rob M J; Rijkers, Dirk T S

    2015-06-01

    Herein the synthesis of two nisin AB dicarba analogs is described, focusing on amino acid modifications at positions 2 and 5. The nisin mimics were synthesized by a combination of solid phase synthesis of the linear peptides, followed by macrocyclization via ring-closing metathesis and fragment assembly by means of solution phase chemistry. The two N-terminal nisin AB-fragment mimics contain either the native dehydrobutyrine (Dhb)/dehydroalanine (Dha) amino acid residues or alanine at position 2 and 5, respectively. The native dehydrobutyrine at position 2 and dehydroalanine at position 5 were introduced as their precursors, namely threonine and serine, respectively, and subsequent dehydration was carried out by EDCI/CuCl as the condensing agent. Both AB-fragment mimics were analyzed in a lipid II binding assay and it was found that the Ala2/Ala5 AB-mimic (2) showed a reduced activity, while the Dhb2/Dha5 AB-mimic (3) was as active as the native AB-fragment (1).

  18. Lipid signaling in plants

    NARCIS (Netherlands)

    Munnik, T.

    2010-01-01

    This book highlights the current status of plant lipid signaling. Written by leading researchers in the field, the chapters include detailed information on the measurement, regulation and function of phospholipases, lipid kinases, lipid phosphatases, inositolpolyphosphates, polyphosphoinositides, ph

  19. Lipid Metabolism Disorders

    Science.gov (United States)

    ... metabolic disorder, something goes wrong with this process. Lipid metabolism disorders, such as Gaucher disease and Tay-Sachs disease, involve lipids. Lipids are fats or fat-like substances. They ...

  20. Plant lipid signaling protocols

    NARCIS (Netherlands)

    Munnik, T.; Heilmann, I.

    2013-01-01

    Eukaryotic cells are surrounded by membranes consisting of various lipids, including sterols, sphingolipids, glycolipids, and phospholipids. Besides structural functions, membranes also contain lipids with regulatory and signaling roles. Such lipids include polyphosphoinositides, the low-abundant

  1. Human Microbiome Inspired Antibiotics with Improved β-Lactam Synergy against MDR Staphylococcus aureus.

    Science.gov (United States)

    Chu, John; Vila-Farres, Xavier; Inoyama, Daigo; Gallardo-Macias, Ricardo; Jaskowski, Mark; Satish, Shruthi; Freundlich, Joel S; Brady, Sean F

    2017-09-11

    The flippase MurJ is responsible for transporting the cell wall intermediate lipid II from the cytoplasm to the outside of the cell. While essential for the survival of bacteria, it remains an underexploited target for antibacterial therapy. The humimycin antibiotics are lipid II flippase (MurJ) inhibitors that were synthesized on the basis of bioinformatic predictions derived from secondary metabolite gene clusters found in the human microbiome. Here, we describe an SAR campaign around humimycin A that produced humimycin 17S. Compared to humimycin A, 17S is a more potent β-lactam potentiator, has a broader spectrum of activity, which now includes both methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecalis (VRE), and did not lead to any detectable resistance when used in combination with a β-lactam. Combinations of β-lactam and humimycin 17S provide a potentially useful long-term MRSA regimen.

  2. Importance of the hexagonal lipid phase in biological membrane organisation

    Directory of Open Access Journals (Sweden)

    Juliette eJouhet

    2013-12-01

    Full Text Available Abstract:Domains are present in every natural membrane. They are characterised by a distinctive protein and/or lipid composition. Their size is highly variable from the nano- to the micrometer scale. The domains confer specific properties to the membrane leading to original structure and function. The determinants leading to domain organisation are therefore important but remain obscure. This review presents how the ability of lipids to organize into hexagonal II or lamellar phases can promote particular local structures within membranes. Since biological membranes are composed of a mixture of lipids, each with distinctive biophysical properties, lateral and transversal sorting of lipids can promote creation of domains inside the membrane through local modulation of the lipid phase. Lipid biophysical properties have been characterized for long based on in vitro analyses using non-natural lipid molecules; their re-examinations using natural lipids might open interesting perspectives on membrane architecture occurring in vivo in various cellular and physiological contexts.

  3. Multiscale molecular modeling of tertiary supported lipid bilayers

    Science.gov (United States)

    Ranz, Holden T.; Faller, Roland

    2015-08-01

    Ternary lipid bilayer systems assembled from mixtures of dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), and cholesterol have been studied using coarse-grained molecular dynamics at biologically relevant temperatures (280 K to 310 K), which are between the chain melting temperatures of the pure lipid component. Free lipid bilayers were simulated using the MARTINI model (Stage I) and a variant with water-water interactions reduced to 76% (Stage II). The latter was subsequently used for preparing supported lipid bilayer simulations (Stage III). Clustering of like lipids was observed, but the simulation timescale did not yield larger phaseseparated domains.

  4. Slow Phospholipid Exchange between a Detergent-Solubilized Membrane Protein and Lipid-Detergent Mixed Micelles: Brominated Phospholipids as Tools to Follow Its Kinetics

    Science.gov (United States)

    Montigny, Cédric; Dieudonné, Thibaud; Orlowski, Stéphane; Vázquez-Ibar, José Luis; Gauron, Carole; Georgin, Dominique; Lund, Sten; le Maire, Marc; Møller, Jesper V.; Champeil, Philippe

    2017-01-01

    by using the Drs2p/Cdc50p complex, a lipid flippase with specific binding sites for lipids. PMID:28118404

  5. Bile acids and lipids in isolated rat hepatocytes. II. Source of cholesterol used for bile acid formation, estimated by incorporation of tritium from tritiated water, and by the effect of ML-236B

    NARCIS (Netherlands)

    Kempen, H.J.; Vos Van Holstein, M.; Lange, J.de

    1983-01-01

    Chemicals/CAS: cholesterol, 57-88-5; cholic acid, 32500-01-9, 361-09-1, 81-25-4; colestyramine, 11041-12-6, 58391-37-0; compactin, 73573-88-3; lipid, 66455-18-3; tritium oxide, 14940-65-9; Bile Acids and Salts; Cholesterol, 57-88-5; Cholestyramine, 11041-12-6; compactin, 73573-88-3; Lipids;

  6. Phytic Acid Inhibits Lipid Peroxidation In Vitro

    Directory of Open Access Journals (Sweden)

    Alicja Zajdel

    2013-01-01

    Full Text Available Phytic acid (PA has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II/ascorbate-induced peroxidation, as well as Fe(II/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100 μM and 500 μM effectively inhibited the decay of linoleic acid, both in the absence and presence of Fe(II/ascorbate. The observed inhibitory effect of PA on Fe(II/ascorbate-induced lipid peroxidation was lower (10–20% compared to that of autoxidation. PA did not change linoleic acid hydroperoxides concentration levels after 24 hours of Fe(II/ascorbate-induced peroxidation. In the absence of Fe(II/ascorbate, PA at 100 μM and 500 μM significantly suppressed decomposition of linoleic acid hydroperoxides. Moreover, PA at the tested nontoxic concentrations (100 μM and 500 μM significantly decreased 4-hydroxyalkenal levels in Caco-2 cells which structurally and functionally resemble the small intestinal epithelium. It is concluded that PA inhibits linoleic acid oxidation and reduces the formation of 4-hydroxyalkenals. Acting as an antioxidant it may help to prevent intestinal diseases induced by oxygen radicals and lipid peroxidation products.

  7. Phytic acid inhibits lipid peroxidation in vitro.

    Science.gov (United States)

    Zajdel, Alicja; Wilczok, Adam; Węglarz, Ludmiła; Dzierżewicz, Zofia

    2013-01-01

    Phytic acid (PA) has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II)/ascorbate-induced peroxidation, as well as Fe(II)/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100 μM and 500 μM effectively inhibited the decay of linoleic acid, both in the absence and presence of Fe(II)/ascorbate. The observed inhibitory effect of PA on Fe(II)/ascorbate-induced lipid peroxidation was lower (10-20%) compared to that of autoxidation. PA did not change linoleic acid hydroperoxides concentration levels after 24 hours of Fe(II)/ascorbate-induced peroxidation. In the absence of Fe(II)/ascorbate, PA at 100 μM and 500 μM significantly suppressed decomposition of linoleic acid hydroperoxides. Moreover, PA at the tested nontoxic concentrations (100 μM and 500 μM) significantly decreased 4-hydroxyalkenal levels in Caco-2 cells which structurally and functionally resemble the small intestinal epithelium. It is concluded that PA inhibits linoleic acid oxidation and reduces the formation of 4-hydroxyalkenals. Acting as an antioxidant it may help to prevent intestinal diseases induced by oxygen radicals and lipid peroxidation products.

  8. cobalt (ii), nickel (ii)

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The manganese (II), cobalt (II), nickel (II) and copper (II) complexes of N, N' – ... temperature and coordinated water were determined ... indicating fairly stable complex compounds (Table 1). The complex compounds are insoluble [Table 2] in water and common organic solvents, but are readily soluble in ...

  9. Genetic architecture of circulating lipid levels

    DEFF Research Database (Denmark)

    Demirkan, Ayşe; Amin, Najaf; Isaacs, Aaron

    2011-01-01

    the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify...... levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from...... suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture...

  10. Doxorubicin Lipid Complex Injection

    Science.gov (United States)

    Doxorubicin lipid complex is used to treat ovarian cancer that has not improved or that has worsened after treatment with other medications. Doxorubicin lipid complex is also used to treat Kaposi's ...

  11. Irinotecan Lipid Complex Injection

    Science.gov (United States)

    Irinotecan lipid complex is used in combination with other medications to treat pancreatic cancer that has spread to other ... worsened after treatment with other chemotherapy medications. Irinotecan lipid complex is in a class of antineoplastic medications ...

  12. Daunorubicin Lipid Complex Injection

    Science.gov (United States)

    Daunorubicin lipid complex is used to treat advanced Kaposi's sarcoma (a type of cancer that causes abnormal tissue to ... body) related to acquired immunodeficiency syndrome (AIDS). Daunorubicin lipid complex is in a class of medications called ...

  13. Vincristine Lipid Complex Injection

    Science.gov (United States)

    Vincristine lipid complex is used to treat a certain type of acute lymphoblastic leukemia (ALL; a type of cancer ... least two different treatments with other medications. Vincristine lipid complex is in a class of medications called ...

  14. Parenteral Nutrition and Lipids.

    Science.gov (United States)

    Raman, Maitreyi; Almutairdi, Abdulelah; Mulesa, Leanne; Alberda, Cathy; Beattie, Colleen; Gramlich, Leah

    2017-04-14

    Lipids have multiple physiological roles that are biologically vital. Soybean oil lipid emulsions have been the mainstay of parenteral nutrition lipid formulations for decades in North America. Utilizing intravenous lipid emulsions in parenteral nutrition has minimized the dependence on dextrose as a major source of nonprotein calories and prevents the clinical consequences of essential fatty acid deficiency. Emerging literature has indicated that there are benefits to utilizing alternative lipids such as olive/soy-based formulations, and combination lipids such as soy/MCT/olive/fish oil, compared with soybean based lipids, as they have less inflammatory properties, are immune modulating, have higher antioxidant content, decrease risk of cholestasis, and improve clinical outcomes in certain subgroups of patients. The objective of this article is to review the history of IVLE, their composition, the different generations of widely available IVLE, the variables to consider when selecting lipids, and the complications of IVLE and how to minimize them.

  15. Lipid exchange by ultracentrifugation

    DEFF Research Database (Denmark)

    Drachmann, Nikolaj Düring; Olesen, Claus

    2014-01-01

    Lipids play an important role in maintaining P-type ATPase structure and function, and often they are crucial for ATPase activity. When the P-type ATPases are in the membrane, they are surrounded by a mix of different lipids species with varying aliphatic chain lengths and saturation......, and the complex interplay between the lipids and the P-type ATPases are still not well understood. We here describe a robust method to exchange the majority of the lipids surrounding the ATPase after solubilisation and/or purification with a target lipid of interest. The method is based on an ultracentrifugation...... step, where the protein sample is spun through a dense buffer containing large excess of the target lipid, which results in an approximately 80-85 % lipid exchange. The method is a very gently technique that maintains protein folding during the process, hence allowing further characterization...

  16. Nutrients and neurodevelopment: lipids.

    Science.gov (United States)

    González, Horacio F; Visentin, Silvana

    2016-10-01

    Nutrients, lipids in particular, make up the central nervous system structure and play major functional roles: they stimulate development, migration, and nerve cell differentiation. They are part of gray matter, white matter, nerve nuclei, and synaptogenesis. Breast milk contains lipids which are crucial for infant brain development. The lipid profile of breast milk was used as a guideline for the development of breast milk substitutes. However, to date, no substitute has matched it. Complementary feeding should include docosahexaenoic acid, arachidonic acid, other polyunsaturated fatty acids, saturated fatty acids, and complex lipids found in milk fat. The lipid composition of breast milk depends on maternal intake and nutritional status during pregnancy and breast-feeding. It has a great impact on development. Our goal is to review scientific literature regarding the role of lipids on infant brain development and the importance of breast milk lipid composition, maternal diet, and complementary feeding.

  17. Lipid Structure in Triolein Lipid Droplets

    DEFF Research Database (Denmark)

    Chaban, Vitaly V; Khandelia, Himanshu

    2014-01-01

    Lipid droplets (LDs) are primary repositories of esterified fatty acids and sterols in animal cells. These organelles originate on the lumenal or cytoplasmic side of endoplasmic reticulum (ER) membrane and are released to the cytosol. In contrast to other intracellular organelles, LDs are composed...... of a mass of hydrophobic lipid esters coved by phospholipid monolayer. The small size and unique architecture of LDs makes it complicated to study LD structure by modern experimental methods. We discuss coarse-grained molecular dynamics (MD) simulations of LD formation in systems containing 1-palmitoyl-2...... to coarse-grained simulations, the presence of PE lipids at the interface has a little impact on distribution of components and on the overall LD structure. (4) The thickness of the lipid monolayer at the surface of the droplet is similar to the thickness of one leaflet of a bilayer. Computer simulations...

  18. Polyene-lipids: a new tool to image lipids

    DEFF Research Database (Denmark)

    Kuerschner, Lars; Ejsing, Christer S.; Ekroos, Kim

    2005-01-01

    conjugated double bonds as a new type of lipid tag. Polyene-lipids exhibit a unique structural similarity to natural lipids, which results in minimal effects on the lipid properties. Analyzing membrane phase partitioning, an important biophysical and biological property of lipids, we demonstrated...... the superiority of polyene-lipids to both NBD- and BODIPY-tagged lipids. Cells readily take up various polyene-lipid precursors and generate the expected end products with no apparent disturbance by the tag. Applying two-photon excitation microscopy, we imaged the distribution of polyene-lipids in living...

  19. Computational studies of plasma lipoprotein lipids.

    Science.gov (United States)

    Pan, Lurong; Segrest, Jere P

    2016-10-01

    Plasma lipoproteins are macromolecular assemblies of proteins and lipids found in the blood. The lipid components of lipoproteins are amphipathic lipids such as phospholipids (PLs), and unesterified cholesterols (UCs) and hydrophobic lipids such as cholesteryl esters (CEs) and triglycerides (TGs). Since lipoproteins are soft matter supramolecular assemblies easily deformable by thermal fluctuations and they also exist in varying densities and protein/lipid components, a detailed understanding of their structure/function is experimentally difficult. Molecular dynamics (MD) simulation has emerged as a particularly promising way to explore the structure and dynamics of lipoproteins. The purpose of this review is to survey the current status of computational studies of the lipid components of the lipoproteins. Computational studies aim to explore three levels of complexity for the 3-dimensional structural dynamics of lipoproteins at various metabolic stages: (i) lipoprotein particles consist of protein with minimal lipid; (ii) lipoprotein particles consist of PL-rich discoidal bilayer-like lipid particles; (iii) mature circulating lipoprotein particles consist of CE-rich or TG-rich spheroidal lipid-droplet-like particles. Due to energy barriers involved in conversion between these species, other biomolecules also participate in lipoprotein biological assembly. For example: (i) lipid-poor apolipoprotein A-I (apoA-I) interacts with ATP-binding cassette transporter A1 (ABCA1) to produce nascent discoidal high density lipoprotein (dHDL) particles; (ii) lecithin-cholesterol acyltransferase (LCAT) mediates the conversion of UC to CE in dHDL, driving spheroidal HDL (sHDL) formation; (iii) transfer proteins, cholesterol ester transfer protein (CETP) and phospholipid transfer protein (PLTP), transfer both CE and TG and PL, respectively, between lipoprotein particles. Computational studies have the potential to explore different lipoprotein particles at each metabolic stage in

  20. Development of a water-in-oil-in-water multiple emulsion system integrating biomimetic aqueous-core lipid nanodroplets for protein entity stabilization. Part II: process and product characterization.

    Science.gov (United States)

    Glasser, Cássia A; Vila, Marta M D C; Pereira, Júlio C; Chaud, Marco V; Oliveira Júnior, José M; Tubino, Matthieu; Balcão, Victor M

    2016-12-01

    The aqueous-core enclosed in lipid nanoballoons integrating multiple emulsions of the type water-in-oil-in-water mimic, at least in theory, the environment within viable cells, thus being suitable for housing hydrophilic protein entities such as bioactive proteins, peptides and bacteriophage particles. This study reports a complete physicochemical characterization of optimized biomimetic aqueous-core lipid nanoballoons housing hydrophilic (BSA) protein entities, evolved from a statistical 2(3)×3(1) factorial design study (three variables at two levels and one variable at three levels) that was the subject of the first paper of a series of three, aiming at complete stabilization of the three-dimensional structure of protein entities attempted via housing the said molecular entities within biomimetic aqueous-core lipid nanoballoons integrating a multiple (W/O/W) emulsion. The statistical factorial design followed led to the production of an optimum W/O/W multiple emulsion possessing quite homogeneous particles with an average hydrodynamic size of (186.2 ± 2.6) nm and average Zeta potential of (-36.5 ± 0.9) mV, and exhibiting a polydispersity index of 0.206 ± 0.014. Additionally, the results obtained for the diffusion coefficient of the lipid nanoballoons integrating the optimized W/O/W multiple emulsion were comparable and of the same order of magnitude (10(-12) m(2) s(-1)) as those published by other authors since, typically, diffusion coefficients for molecules range from 10(-10) to 10(-7) m(2) s(-1), but diffusion coefficients for nanoparticles are typically of the order of magnitude of 10(-12) m(2) s(-1).

  1. Silica-lipid hybrid microcapsules: influence of lipid and emulsifier type on in vitro performance.

    Science.gov (United States)

    Lim, Li Hui; Tan, Angel; Simovic, Spomenka; Prestidge, Clive A

    2011-05-16

    This study reports on the physicochemical characterisation and in vitro investigations of macro-porous silica-lipid hybrid (SLH) microcapsules when formulated using various lipids: long-chain triglycerides (LCT), medium-chain triglycerides (MCT), medium-chain mono-, diglycerides (MCMDG); and emulsifiers: anionic lecithin and cationic oleylamine. For the lipophilic compound coumarin 102 (logP=4.09), a complete and immediate in vitro release was attained for the SLH microcapsules under simulated intestinal sink conditions. The in vitro digestion study of various types of SLH microcapsules demonstrates: (i) reduced variability and enhanced lipid digestibility for the MCMDG-based microcapsules (i.e. 90-100% lipolysis) in comparison with an equivalent lipid solution and emulsion (50-90% lipolysis); and (ii) more controllable digestion kinetics for the LCT-based microcapsules which produce a lipolysis rate higher than that of a lipid solution but lower than that of a lipid emulsion. The drug phase partition results show approximately 5- to 17-fold increase in the drug solubilisation degree resulting from the digestion of MCT and MCMDG-based microcapsules (116 μg/mL), and LCT-based microcapsules (416 μg/mL) in comparison with the blank micellar medium (24 μg/mL). In conclusion, the SLH microcapsules could be tailored to manipulate the digestion patterns of both medium- and long-chain lipids in order to maximise the drug solubilisation capacity. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Lipid bilayers and interfaces

    NARCIS (Netherlands)

    Kik, R.A.

    2007-01-01

    In biological systems lipid bilayers are subject to many different interactions with other entities. These can range from proteins that are attached to the hydrophilic region of the bilayer or transmembrane proteins that interact with the hydrophobic region of the lipid bilayer. Interaction between

  3. Lipids and lipid binding proteins: a perfect match.

    Science.gov (United States)

    Glatz, Jan F C

    2015-02-01

    Lipids serve a great variety of functions, ranging from structural components of biological membranes to signaling molecules affecting various cellular functions. Several of these functions are related to the unique physico-chemical properties shared by all lipid species, i.e., their hydrophobicity. The latter, however, is accompanied by a poor solubility in an aqueous environment and thus a severe limitation in the transport of lipids in aqueous compartments such as blood plasma and the cellular soluble cytoplasm. Specific proteins which can reversibly and non-covalently associate with lipids, designated as lipid binding proteins or lipid chaperones, greatly enhance the aqueous solubility of lipids and facilitate their transport between tissues and within tissue cells. Importantly, transport of lipids across biological membranes also is facilitated by specific (membrane-associated) lipid binding proteins. Together, these lipid binding proteins determine the bio-availability of their ligands, and thereby markedly influence the subsequent processing, utilization, or signaling effect of lipids. The bio-availability of specific lipid species thus is governed by the presence of specific lipid binding proteins, the affinity of these proteins for distinct lipid species, and the presence of competing ligands (including pharmaceutical compounds). Recent studies suggest that post-translational modifications of lipid binding proteins may have great impact on lipid-protein interactions. As a result, several levels of regulation exist that together determine the bio-availability of lipid species. This short review discusses the significance of lipid binding proteins and their potential application as targets for therapeutic intervention.

  4. Aqueous extracts of two varieties of ginger (Zingiber officinale) inhibit angiotensin I-converting enzyme, iron(II), and sodium nitroprusside-induced lipid peroxidation in the rat heart in vitro.

    Science.gov (United States)

    Akinyemi, Ayodele J; Ademiluyi, Adedayo O; Oboh, Ganiyu

    2013-07-01

    Ginger has reportedly been used in folk medicine for the management and prevention of hypertension and other cardiovascular diseases. Therefore, this study sought to investigate the inhibitory effect of aqueous extracts of two varieties of ginger on a key enzyme linked to hypertension (angiotensin I-converting enzyme [ACE]), and on pro-oxidants [Fe(2+) and sodium nitroprusside (SNP)] which have been shown to induce lipid peroxidation in the rat's isolated heart in vitro. Aqueous extracts (0.05 mg/mL) of red ginger (Zingiber officinale var. Rubra) and white ginger (Zingiber officinale Roscoe) were prepared and the ability of the extracts to inhibit ACE along with Fe(2+)- and SNP-induced lipid peroxidation was determined in rat's heart in vitro. Results revealed that both extracts inhibited ACE in a dose-dependent manner (25-125 μg/mL). However, red ginger extract (EC50=27.5 μg/mL) had a significantly (Pginger extract (EC50=87.0 μg/mL). Furthermore, incubation of the rat's heart in the presence of Fe(2+) and SNP caused a significant increase (Pginger extracts (78-313 μg/mL) caused a dose-dependent decrease in the MDA content of the stressed heart homogenates. This suggests that the possible mechanism through which ginger exerts its antihypertensive properties may be through inhibition of ACE activity and prevention of lipid peroxidation in the heart. Furthermore, red ginger showed stronger inhibition of ACE than white ginger. Additionally, it should be noted that these protective properties of the ginger varieties could be attributed to their polyphenol contents.

  5. Big, Fat World of Lipids

    Science.gov (United States)

    ... Science Home Page The Big, Fat World of Lipids By Emily Carlson Posted August 9, 2012 Cholesterol ... ways to diagnose and treat lipid-related conditions. Lipid Encyclopedia Just as genomics and proteomics spurred advances ...

  6. Rosiglitazone and Fenofibrate Additive Effects on Lipids

    Science.gov (United States)

    2011-10-01

    fasting TG, high-density lipoprotein cholesterol ( HDL -C), LDL -C, and plasma apolipoproteins A-I, A-II, and C-III level were compared after 12 weeks of...2 diabetic patients, the mean HDL -C increased by 6% and TG by 2%. The increase in the LDL -C concentration (9%) was accompanied by a shift in small...transaminases, fasting lipid profile, apolipoproteins, HDL size, LDL size, and statistical differ- ence from baseline. At this visit, subjects were

  7. Phytic Acid Inhibits Lipid Peroxidation In Vitro

    OpenAIRE

    Alicja Zajdel; Adam Wilczok; Ludmiła Węglarz; Zofia Dzierżewicz

    2013-01-01

    Phytic acid (PA) has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II)/ascorbate-induced peroxidation, as well as Fe(II)/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100 μM and 500 μM effectively inhibited the deca...

  8. Avanti lipid tools: connecting lipids, technology, and cell biology.

    Science.gov (United States)

    Sims, Kacee H; Tytler, Ewan M; Tipton, John; Hill, Kasey L; Burgess, Stephen W; Shaw, Walter A

    2014-08-01

    Lipid research is challenging owing to the complexity and diversity of the lipidome. Here we review a set of experimental tools developed for the seasoned lipid researcher, as well as, those who are new to the field of lipid research. Novel tools for probing protein-lipid interactions, applications for lipid binding antibodies, enhanced systems for the cellular delivery of lipids, improved visualization of lipid membranes using gold-labeled lipids, and advances in mass spectrometric analysis techniques will be discussed. Because lipid mediators are known to participate in a host of signal transduction and trafficking pathways within the cell, a comprehensive lipid toolbox that aids the science of lipidomics research is essential to better understand the molecular mechanisms of interactions between cellular components. This article is part of a Special Issue entitled Tools to study lipid functions.

  9. Altered lipid composition in cortical lipid rafts occurs at early stages of sporadic Alzheimer's disease and facilitates APP/BACE1 interactions.

    Science.gov (United States)

    Fabelo, Noemí; Martín, Virginia; Marín, Raquel; Moreno, Dolores; Ferrer, Isidre; Díaz, Mario

    2014-08-01

    The presence of lipid alterations in lipid rafts from the frontal cortex in late stages of Alzheimer's disease (AD) has been recently demonstrated. Here, we have isolated and analyzed the lipid composition of lipid rafts from different brain areas from control and AD subjects at initial neuropathologic stages. We have observed that frontal cortex lipid rafts are profoundly altered in AD brains from the earliest stages of AD, namely AD I/II. These changes in the lipid matrix of lipid rafts affected both lipid classes and fatty acids and were also detected in the entorhinal cortex, but not in the cerebellum from the same subjects. Paralleling these changes, lipid rafts from AD frontal and entorhinal cortices displayed higher anisotropy for environment-sensitive probes, indicating that lipid changes in AD lipid rafts increased membrane order and viscosity in these domains. The pathophysiological consequences of these alterations in the development and progression of AD were strengthened by the significant, and specific, accumulation of β-secretase within the lipid rafts of AD subjects even at the earliest stages. Our results provide a mechanistic connection between lipid alterations in these microdomains and amyloidogenic processing of amyloid precursor protein.

  10. Regulation of lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    Peng LI

    2011-01-01

    @@ Lipids including cholesterol, phospholipids, fatty acids and triacylglycerols are important cellular constituents involved in membrane structure, energy homeostasis and many biological processes such as signal transduction, organelle development and cell differentiation.Recently, the area of lipid metabolism has drawn a great deal of attention due to its emerging role in the development of metabolic disorders such as obesity, diabetes, atherosclerosis and liver steatosis.We decided to organize a special issue of Frontiers in Biology focusing on our current understanding of lipid metabolism.

  11. Lake Superior lipids

    Science.gov (United States)

    Fish chemistry data (d13C, d15N, C:N, lipid content) published in Rapid Commun. Mass Spectrom. 2015, 29, 2069??2077 DOI: 10.1002/rcm.7367This dataset is associated with the following publication:Hoffman , J., M. Sierszen , and A. Cotter. Fish tissue lipid-C:N relationships for correcting ä13C values and estimating lipid content in aquatic food web studies. Rapid Communications in Mass Spectrometry. Wiley InterScience, Silver Spring, MD, USA, 29(21): 2069–2077, (2015).

  12. Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation.

    Science.gov (United States)

    Laugerette, Fabienne; Vors, Cécile; Peretti, Noël; Michalski, Marie-Caroline

    2011-01-01

    Metabolic diseases such as obesity are characterized by a subclinical inflammatory state that contributes to the development of insulin resistance and atherosclerosis. Recent reports also indicate that (i) there are alterations of the intestinal microbiota in metabolic diseases and (ii) absorption of endogenous endotoxins (namely lipopolysaccharides, LPS) can occur, particularly during the digestion of lipids. The aim of the present review is to highlight recently gained knowledge regarding the links between high fat diets, lipid digestion, intestinal microbiota and metabolic endotoxemia & inflammation.

  13. Multiscale structures of lipids in foods as parameters affecting fatty acid bioavailability and lipid metabolism.

    Science.gov (United States)

    Michalski, M C; Genot, C; Gayet, C; Lopez, C; Fine, F; Joffre, F; Vendeuvre, J L; Bouvier, J; Chardigny, J M; Raynal-Ljutovac, K

    2013-10-01

    On a nutritional standpoint, lipids are now being studied beyond their energy content and fatty acid (FA) profiles. Dietary FA are building blocks of a huge diversity of more complex molecules such as triacylglycerols (TAG) and phospholipids (PL), themselves organised in supramolecular structures presenting different thermal behaviours. They are generally embedded in complex food matrixes. Recent reports have revealed that molecular and supramolecular structures of lipids and their liquid or solid state at the body temperature influence both the digestibility and metabolism of dietary FA. The aim of the present review is to highlight recent knowledge on the impact on FA digestion, absorption and metabolism of: (i) the intramolecular structure of TAG; (ii) the nature of the lipid molecules carrying FA; (iii) the supramolecular organization and physical state of lipids in native and formulated food products and (iv) the food matrix. Further work should be accomplished now to obtain a more reliable body of evidence and integrate these data in future dietary recommendations. Additionally, innovative lipid formulations in which the health beneficial effects of either native or recomposed structures of lipids will be taken into account can be foreseen.

  14. 443 Review Lipids

    African Journals Online (AJOL)

    Marinda

    2009-07-20

    Jul 20, 2009 ... Keywords: lipid emulsion therapy; local anaesthetic toxicity; local anaesthetic cardiotoxicity; .... of particular importance in generating sufficient ATP from fats because ..... Propofol is poorly water soluble and is dissolved in the.

  15. Metabolism. Part III: Lipids.

    Science.gov (United States)

    Bodner, George M.

    1986-01-01

    Describes the metabolic processes of complex lipids, including saponification, activation and transport, and the beta-oxidation spiral. Discusses fatty acid degradation in regard to biochemical energy and ketone bodies. (TW)

  16. Lipid-modifying therapy

    African Journals Online (AJOL)

    2009-03-20

    Mar 20, 2009 ... risk reduction for most patients, while patients with severe ... He runs the Diabetic, Endocrine and Lipid clinics at R K Khan Hospital. Treatment .... retinopathy requiring laser therapy). ... Despite knowledge of the risk factors for.

  17. Challenges in the theoretical investigations of lipid membrane configurations

    Institute of Scientific and Technical Information of China (English)

    Tu Zhan-Chun

    2013-01-01

    We report some key results in the theoretical investigations of configurations of lipid membranes and present several challenges in this field,which involve (i) the exact solutions to the shape equation of lipid vesicles,(ii) the exact solutions to the governing equations of open lipid membranes,(iii) the neck condition of two-phase vesicles in the budding state,(iv)the nonlocal theory of membrane elasticity,and (v) the relationship between the symmetry and the magnitude of the free energy.

  18. Lipids of mitochondria.

    Science.gov (United States)

    Horvath, Susanne E; Daum, Günther

    2013-10-01

    A unique organelle for studying membrane biochemistry is the mitochondrion whose functionality depends on a coordinated supply of proteins and lipids. Mitochondria are capable of synthesizing several lipids autonomously such as phosphatidylglycerol, cardiolipin and in part phosphatidylethanolamine, phosphatidic acid and CDP-diacylglycerol. Other mitochondrial membrane lipids such as phosphatidylcholine, phosphatidylserine, phosphatidylinositol, sterols and sphingolipids have to be imported. The mitochondrial lipid composition, the biosynthesis and the import of mitochondrial lipids as well as the regulation of these processes will be main issues of this review article. Furthermore, interactions of lipids and mitochondrial proteins which are highly important for various mitochondrial processes will be discussed. Malfunction or loss of enzymes involved in mitochondrial phospholipid biosynthesis lead to dysfunction of cell respiration, affect the assembly and stability of the mitochondrial protein import machinery and cause abnormal mitochondrial morphology or even lethality. Molecular aspects of these processes as well as diseases related to defects in the formation of mitochondrial membranes will be described. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery.

    Science.gov (United States)

    Cheng, Xinwei; Lee, Robert J

    2016-04-01

    Lipid nanoparticles (LNPs) have shown promise as delivery vehicles for therapeutic oligonucleotides, including antisense oligos (ONs), siRNA, and microRNA mimics and inhibitors. In addition to a cationic lipid, LNPs are typically composed of helper lipids that contribute to their stability and delivery efficiency. Helper lipids with cone-shape geometry favoring the formation hexagonal II phase, such as dioleoylphosphatidylethanolamine (DOPE), can promote endosomal release of ONs. Meanwhile, cylindrical-shaped lipid phosphatidylcholine can provide greater bilayer stability, which is important for in vivo application of LNPs. Cholesterol is often included as a helper that improves intracellular delivery as well as LNP stability in vivo. Inclusion of a PEGylating lipid can enhance LNP colloidal stability in vitro and circulation time in vivo but may reduce uptake and inhibit endosomal release at the cellular level. This problem can be addressed by choosing reversible PEGylation in which the PEG moiety is gradually released in blood circulation. pH-sensitive anionic helper lipids, such as fatty acids and cholesteryl hemisuccinate (CHEMS), can trigger low-pH-induced changes in LNP surface charge and destabilization that can facilitate endosomal release of ONs. Generally speaking, there is no correlation between LNP activity in vitro and in vivo because of differences in factors limiting the efficiency of delivery. Designing LNPs requires the striking of a proper balance between the need for particle stability, long systemic circulation time, and the need for LNP destabilization inside the target cell to release the oligonucleotide cargo, which requires the proper selection of both the cationic and helper lipids. Customized design and empirical optimization is needed for specific applications.

  20. Omental Lipid-Coated Mesh

    Science.gov (United States)

    2011-06-16

    civilian medicine. REFERENCES: 1. Takada T, Kamei Y, Iwata T, et al. Effect of Omental Lipid Fraction on Enhancement of Skin Flap Survival. Annals of...Characterization of Feline Omentum Lipids. Lipids, 1987; 22:229-235. 7. Nottebaert M, Lane J, Juhn A, et al. Omental Angiogenic Lipid Fraction and

  1. Heart, lipids and hormones

    Directory of Open Access Journals (Sweden)

    Peter Wolf

    2017-05-01

    Full Text Available Cardiovascular disease is the leading cause of death in general population. Besides well-known risk factors such as hypertension, impaired glucose tolerance and dyslipidemia, growing evidence suggests that hormonal changes in various endocrine diseases also impact the cardiac morphology and function. Recent studies highlight the importance of ectopic intracellular myocardial and pericardial lipid deposition, since even slight changes of these fat depots are associated with alterations in cardiac performance. In this review, we overview the effects of hormones, including insulin, thyroid hormones, growth hormone and cortisol, on heart function, focusing on their impact on myocardial lipid metabolism, cardiac substrate utilization and ectopic lipid deposition, in order to highlight the important role of even subtle hormonal changes for heart function in various endocrine and metabolic diseases.

  2. LIPID PEROXIDATION IN PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    T.Sharmila Krishna

    2015-03-01

    Full Text Available Hypertension in pregnancy is a leading cause of both maternal and fetal mortality and morbidity. Preeclampsia is characterised by hypertension and proteinuria. Lipid peroxidation is an important factor in the pathophysiology of Preeclampsia. The present study was undertaken to determine Serum Malondialdehyde (MDA levels , a product of lipid peroxidation , in clinically diagnosed Preeclamptic women(n=30 and the values were compared with that of Normotensive pregnant women (n=30 aged between 18-30yrs. All of them were in their third trimester and were primigravida. Serum MDA was estimated by TBARS (thiobarbituric acid reactive substances method. We observed that Serum MDA levels were significantly increased in Preeclamptic women (p <0.000 as compared to that of Normotensive pregnant women . Increased levels of lipid peroxiation product - MDA may contribute to the pathophysiology of Preeclampsia.

  3. Lipid Ion Channels

    CERN Document Server

    Heimburg, Thomas

    2010-01-01

    The interpretation electrical phenomena in biomembranes is usually based on the assumption that the experimentally found discrete ion conduction events are due to a particular class of proteins called ion channels while the lipid membrane is considered being an inert electrical insulator. The particular protein structure is thought to be related to ion specificity, specific recognition of drugs by receptors and to macroscopic phenomena as nerve pulse propagation. However, lipid membranes in their chain melting regime are known to be highly permeable to ions, water and small molecules, and are therefore not always inert. In voltage-clamp experiments one finds quantized conduction events through protein-free membranes in their melting regime similar to or even undistinguishable from those attributed to proteins. This constitutes a conceptual problem for the interpretation of electrophysiological data obtained from biological membrane preparations. Here, we review the experimental evidence for lipid ion channels...

  4. Bioorthogonal chemical reporters for analyzing protein lipidation and lipid trafficking.

    Science.gov (United States)

    Hang, Howard C; Wilson, John P; Charron, Guillaume

    2011-09-20

    Protein lipidation and lipid trafficking control many key biological functions in all kingdoms of life. The discovery of diverse lipid species and their covalent attachment to many proteins has revealed a complex and regulated network of membranes and lipidated proteins that are central to fundamental aspects of physiology and human disease. Given the complexity of lipid trafficking and the protein targeting mechanisms involved with membrane lipids, precise and sensitive methods are needed to monitor and identify these hydrophobic molecules in bacteria, yeast, and higher eukaryotes. Although many analytical methods have been developed for characterizing membrane lipids and covalently modified proteins, traditional reagents and approaches have limited sensitivity, do not faithfully report on the lipids of interest, or are not readily accessible. The invention of bioorthogonal ligation reactions, such as the Staudinger ligation and azide-alkyne cycloadditions, has provided new tools to address these limitations, and their use has begun to yield fresh insight into the biology of protein lipidation and lipid trafficking. In this Account, we discuss how these new bioorthogonal ligation reactions and lipid chemical reporters afford new opportunities for exploring the biology of lipid-modified proteins and lipid trafficking. Lipid chemical reporters from our laboratory and several other research groups have enabled improved detection and large-scale proteomic analysis of fatty-acylated and prenylated proteins. For example, fatty acid and isoprenoid chemical reporters in conjunction with bioorthogonal ligation methods have circumvented the limited sensitivity and hazards of radioactive analogues, allowing rapid and robust fluorescent detection of lipidated proteins in all organisms tested. These chemical tools have revealed alterations in protein lipidation in different cellular states and are beginning to provide unique insights in mechanisms of regulation. Notably, the

  5. How proteins move lipids and lipids move proteins

    NARCIS (Netherlands)

    Sprong, H.|info:eu-repo/dai/nl/222364815; van der Sluijs, P.; van Meer, G.|info:eu-repo/dai/nl/068570368

    2001-01-01

    Cells determine the bilayer characteristics of different membranes by tightly controlling their lipid composition. Local changes in the physical properties of bilayers, in turn, allow membrane deformation, and facilitate vesicle budding and fusion. Moreover, specific lipids at specific locations

  6. Scavenger receptor AI/II truncation, lung function and COPD

    DEFF Research Database (Denmark)

    Thomsen, M; Nordestgaard, B G; Tybjaerg-Hansen, A

    2011-01-01

    The scavenger receptor A-I/II (SRA-I/II) on alveolar macrophages is involved in recognition and clearance of modified lipids and inhaled particulates. A rare variant of the SRA-I/II gene, Arg293X, truncates the distal collagen-like domain, which is essential for ligand recognition. We tested whet...

  7. Organizing MHC Class II Presentation

    Directory of Open Access Journals (Sweden)

    David R Fooksman

    2014-04-01

    Full Text Available Major histocompatibility complex (MHC class II molecules are ligands for CD4+ T cells and are critical for initiating the adaptive immune response. This review is focused on what is currently known about MHC class II organization at the plasma membrane of antigen presenting cells and how this affects antigen presentation to T cells. The organization and diffusion of class II molecules have been measured by a variety of biochemical and microscopic techniques. Membrane lipids and other proteins have been implicated in MHC class II organization and function. However, when compared with the organization of MHC class I or TCR complexes, much less is known about MHC class II. Since clustering of T cell receptors occurs during activation, the organization of MHC molecules prior to recognition and during synapse formation may be critical for antigen presentation.

  8. Lipid Therapy for Intoxications

    NARCIS (Netherlands)

    Robben, Joris Henricus; Dijkman, Marieke Annet

    2017-01-01

    This review discusses the use of intravenous lipid emulsion (ILE) in the treatment of intoxications with lipophilic agents in veterinary medicine. Despite growing scientific evidence that ILE has merit in the treatment of certain poisonings, there is still uncertainty on the optimal composition of t

  9. Lipids in cheese

    Science.gov (United States)

    Lipids are present in cheese at levels above 20 percent and are analyzed by several techniques. Scanning electron microscopy and confocal laser scanning microscopy are used to examine the microstructure, gas chromatography is employed to look at fatty acid composition, and differential scanning cal...

  10. Lipid Therapy for Intoxications

    NARCIS (Netherlands)

    Robben, Joris Henricus; Dijkman, Marieke Annet

    2017-01-01

    This review discusses the use of intravenous lipid emulsion (ILE) in the treatment of intoxications with lipophilic agents in veterinary medicine. Despite growing scientific evidence that ILE has merit in the treatment of certain poisonings, there is still uncertainty on the optimal composition of t

  11. Partitioning of hydrophobic organic contaminants between polymer and lipids for two silicones and low density polyethylene

    DEFF Research Database (Denmark)

    Smedes, Foppe; Rusina, Tatsiana P.; Beeltje, Henry

    2017-01-01

    concentrations in other (defined) media, which however requires appropriate polymer to media partition coefficients. We determined thus polymer-lipid partition coefficients (KPL) of various PCB, PAH and organochlorine pesticides by equilibration of two silicones and low density polyethylene (LDPE) with fish oil...... and Triolein at 4 °C and 20 °C. We observed (i) that KPL was largely independent of lipid type and temperature, (ii) that lipid diffusion rates in the polymers were higher compared to predictions based on their molecular volume, (iii) that silicones showed higher lipid diffusion and lower lipid sorption...... compared to LDPE and (iv) that absorbed lipid behaved like a co-solute and did not affect the partitioning of HOC at least for the smaller molecular size HOC. The obtained KPL can convert measured equilibrium concentrations in passive sampling polymers into equilibrium concentrations in lipid, which...

  12. Amphotericin B Lipid Complex Injection

    Science.gov (United States)

    Amphotericin B lipid complex injection is used to treat serious, possibly life-threatening fungal infections in people who did not respond ... to tolerate conventional amphotericin B therapy. Amphotericin B lipid complex injection is in a class of medications ...

  13. Solid lipid excipients - matrix agents for sustained drug delivery.

    Science.gov (United States)

    Rosiaux, Yvonne; Jannin, Vincent; Hughes, Sophie; Marchaud, Delphine

    2014-08-28

    Lipid excipients are attracting interest from drug developers due to their performance, ease of use, versatility and their potential to generate intellectual property through innovation in drug delivery particularly in the case of modifying drug release systems. Many articles have described the use of lipid excipients to develop matrix modified release dosage forms in a range of processing techniques, therefore a comprehensive review is timely to collect together and analyze key information. This review article focuses on the utility of lipid excipients in solid sustained drug delivery systems with emphasis on the efficiency and robustness of these systems with respect to: (i) the choice of the manufacturing process and impact on drug release, (ii) the fundamental drug release mechanisms, (iii) resistance of the drug formulation under physiological conditions and (iv) long-term stability. Understanding the functionality of these versatile excipients in formulation is elementary for the development of highly robust lipid-based sustained release medicines.

  14. Lipid nanotube or nanowire sensor

    Science.gov (United States)

    Noy, Aleksandr; Bakajin, Olgica; Letant, Sonia; Stadermann, Michael; Artyukhin, Alexander B.

    2009-06-09

    A sensor apparatus comprising a nanotube or nanowire, a lipid bilayer around the nanotube or nanowire, and a sensing element connected to the lipid bilayer. Also a biosensor apparatus comprising a gate electrode; a source electrode; a drain electrode; a nanotube or nanowire operatively connected to the gate electrode, the source electrode, and the drain electrode; a lipid bilayer around the nanotube or nanowire, and a sensing element connected to the lipid bilayer.

  15. Lanolin-derived lipid mixtures mimic closely the lipid composition and organization of vernix caseosa lipids.

    Science.gov (United States)

    Rissmann, Robert; Oudshoorn, Marion H M; Kocks, Elise; Hennink, Wim E; Ponec, Maria; Bouwstra, Joke A

    2008-10-01

    The aim of the present study was to use semi-synthetic lipid mixtures to mimic the complex lipid composition, organization and thermotropic behaviour of vernix caseosa (VC) lipids. As VC shows multiple protecting and barrier supporting properties before and after birth, it is suggested that a VC substitute could be an innovative barrier cream for barrier deficient skin. Lanolin was selected as the source of the branched chain sterol esters and wax esters--the main lipid classes of VC. Different lipid fractions were isolated from lanolin and subsequently mixed with squalene, triglycerides, cholesterol, ceramides and fatty acids to generate semi-synthetic lipid mixtures that mimic the lipid composition of VC, as established by high-performance thin-layer chromatography. Differential scanning calorimetry and Fourier transform infrared spectroscopy investigations revealed that triglycerides play an important role in the (lateral) lipid organization and thermotropic behaviour of the synthetic lipid mixtures. Excellent resemblance of VC lipids was obtained when adding unsaturated triglycerides. Moreover, these lipid mixtures showed similar long range ordering as VC. The optimal lipid mixture was evaluated on tape-stripped hairless mouse skin in vivo. The rate of barrier recovery was increased and comparable to VC lipid treatment.

  16. Lipid characterization of human saliva.

    Science.gov (United States)

    Defagó, Maria Daniela; Valentich, Mirta Ana; Actis, Adriana Beatriz

    2011-12-01

    Salivary lipids have been scarcely studied, and the reported results present disparities. This literature review is presented based on the importance of saliva as a diagnostic and/or prognostic medium for various diseases, its lipid content, and on its potential use for the analysis of nutritional markers that contribute to the study of diseases related to lipid consumption and metabolism.

  17. Relation between plasma and brain lipids

    DEFF Research Database (Denmark)

    Wellington, Cheryl L; Frikke-Schmidt, Ruth

    2016-01-01

    : Plasma levels of traditional lipids and lipoproteins are not consistently associated with risk of dementia even though low plasma levels of apolipoprotein E, through unknown mechanisms, robustly predict future dementia. Experimental evidence suggests neuroprotective roles of several brain...... and cerebrospinal fluid apolipoproteins. Whether plasma levels of apolipoprotein E, or any other apolipoprotein with possible central nervous system and/or blood-brain barrier functions (apolipoproteins J, A-I, A-II, A-IV, D, C-I, and C-III) may become accessible biomarker components that improve risk prediction...

  18. Protein,carbohydrate and lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930463 The relation of polymorphism of LDLreceptor gene with serum cholesterol levels.FAN Leming(范乐明),et al.Atherosclerosis ResCenter,Nanjing Med Coll,Nanjing,210029.NatlMed J China 1993;73(4):242—244.PvuII polymorphism of LDL receptor gene andserum lipid levels were analysed in 115 nor-molipidemic subjects and 57 individuals with hy-percholesterolemia.A significant relationshipwas found between P2 allele and lower serumcholesterol level,suggesting that the LDL recep-tor might contribute to the variation in choles-terol levels in normolipidemic population.Al-

  19. Lipid domains in bicelles containing unsaturated lipids and cholesterol.

    Science.gov (United States)

    Cho, Hyo Soon; Dominick, Johnna L; Spence, Megan M

    2010-07-22

    We have created a stable bicelle system capable of forming micrometer-scale lipid domains that orient in a magnetic field, suitable for structural biology determination in solid-state NMR. The bicelles consisted of a mixture of cholesterol, saturated lipid (DMPC), and unsaturated lipid (POPC), a mixture commonly used to create domains in model membranes, along with a short chain lipid (DHPC) that allows formation of the bicelle phase. While maintaining a constant molar ratio of long to short chain lipids, q = ([POPC]+[DMPC])/[DHPC] = 3, we varied the concentrations of the unsaturated lipid, POPC, and cholesterol to observe the effects of the components on bicelle stability. Using (31)P solid-state NMR, we observed that unsaturated lipids (POPC) greatly destabilized the alignment of the membranes in the magnetic field, while cholesterol stabilized their alignment. By combining cholesterol and unsaturated lipids in the bicelles, we created membranes aligning uniformly in the magnetic field, despite very high concentrations of unsaturated lipids. These bicelles, with high concentrations of both cholesterol and unsaturated lipid, showed similar phase behavior to bicelles commonly used in structural biology, but aligned over a wider temperature range (291-314 K). Domains were observed by measuring time-dependent diffusion constants reflecting restricted diffusion of the lipids within micrometer-scale regions of the bicelles. Micron-scale domains have never been observed in POPC/DMPC/cholesterol vesicles, implying that bilayers in bicelles show different phase behavior than their counterparts in vesicles, and that bilayers in bicelles favor domain formation.

  20. Stability of lipid excipients in solid lipid nanoparticles.

    Science.gov (United States)

    Radomska-Soukharev, Anna

    2007-07-10

    The paper is devoted to the investigation of chemical stability of lipids used as excipients in the production of Solid Lipid Nanoparticles (SLN). Different lipids and amounts of surfactants were considered. Most of the formulations were produced using identical binary surfactant mixtures and concentrations to analyze the effect of the chemical nature of the lipids on their stability in SLN. In some formulations, surfactants were exchanged or their concentration was increased to assess the contribution of surfactants on stability of lipids particles. Solid Lipid Nanoparticles were characterized by photon correlation spectroscopy, laser diffractometry, zeta potential determination and differential scanning calorimetry. Potential effects of lipid crystallinity and modifications were assessed. A gas chromatography (GC) analysis in combination with a method for lipid extraction from aqueous SLN dispersions was used to investigate the chemical stability of the lipid excipients forming the particle matrix. All formulations were produced by the hot homogenization technique. The production process of SLN itself did not affect the chemical stability of lipid excipient forming the particle matrix. The formulations where lipids consisted of trigylicerides showed a negligible decomposition of the structure during incubation at 25 degrees C. Dynasan 118 showed the highest chemical stability (loss<4%) within two years.

  1. Dysregulated lipid metabolism in cancer

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells. The changes of expression and activity of lipid metabolizing enzymes are directly regulated by the activity of oncogenic signals. The dependence of tumor cells on the dysregulated lipid metabolism suggests that proteins involved in this process are excellent chemotherapeutic targets for cancer treatment. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered lipid metabolic pathways in cancer cells. Further understanding of dysregulated lipid metabolism and its associated signaling pathways will help us to better design efficient cancer therapeutic strategy.

  2. Effects of Ferulago angulata Extract on Serum Lipids and Lipid Peroxidation

    Directory of Open Access Journals (Sweden)

    Mahmoud Rafieian-kopaei

    2014-01-01

    Full Text Available Background. Nowadays, herbs they are considered to be the main source of effective drugs for lowering serum lipids and lipid peroxidation. The present experimental animal study aimed to assess the impact of Ferulago angulata on serum lipid profiles, and on levels of lipid peroxidation. Methods. Fifty male Wistar rats, weighing 250–300 g, were randomly divided into five equal groups (ten rats in each. The rat groups received different diets as follows: Group I: fat-rich diet; Group II: fat-rich diet plus hydroalcoholic extracts of Ferulago angulata at a dose of 400 mg/kg; Group III: fat-rich diet plus hydroalcoholic extracts of Ferulago angulata at a dose of 600 mg/kg; Group IV: fat-rich diet plus atorvastatin; Group V: common stock diet. The levels of serum glucose and lipids and the atherogenic index were measured. In addition, malondialdehyde (MDA, thiol oxidation, carbonyl concentrations, C-reactive proteins, and antioxidant capacity were evaluated in each group of rats. Results. Interestingly, by adding a hydroalcoholic extract of Ferulago angulata to the high-fat diet, the levels of total cholesterol and low-density lipoproteins (LDL in the high-fat diet rats were both significantly reduced. This result was considerably greater compared to when atorvastatin was added as an antilipid drug. The beneficial effects of the Ferulago angulata extract on lowering the level of triglycerides was observed only when a high dosage of this plant extraction was added to a high fat diet. Furthermore, the level of malondialdehyde, was significantly affected by the use of the plant extract in a high-fat diet, compared with a normal regimen or high-fat diet alone. Conclusion. Administration of a hydroalcoholic extract of Ferulago angulata can reduce serum levels of total cholesterol, triglycerides, and LDL. It can also inhibit lipid peroxidation.

  3. Lipids and immune function.

    Science.gov (United States)

    Vitale, J J; Broitman, S A

    1981-09-01

    There is in vitro and in vivo evidence to suggest that dietary lipids play a role in modulating immune function. A review of the current literature on the interrelationships among dietary lipids, blood cholesterol levels, immunosuppression, and tumorigenesis makes for a very strong argument that (a) immunosuppression may be causally related to lymphoproliferative disorders, as well as to tumorigenesis and (b) diets high in polyunsaturated fat, relative to diets high in saturated fat, are more immunosuppressive and are better promotors of tumorigenesis. The effects of dietary fat on immune function seem to be mediated though its component parts, the unsaturated fatty acids, specially linoleic, linolenic, and arachidonic. It is not clear how these components affect immune function. Several studies suggest that one effect is mediated by altering the lipid component of the cell membrane and thus its fluidity; the more fluid the membrane, the less responsive it is. Thus, fluidity of both immune cells and those to be destroyed or protected may be affected. The effects of saturated as well as unsaturated fatty acids may be mediated by modulating serum lipoprotein levels, prostaglandin metabolism, and cholesterol concentrations and metabolism.

  4. Tear Film Lipids

    Science.gov (United States)

    Butovich, Igor A.

    2013-01-01

    Human meibomian gland secretions (MGS, or meibum) are formed from a complex mixture of lipids of different classes such as wax esters, cholesteryl esters, (O-acyl)-ω-hydroxy fatty acids (OAHFA) and their esters, acylglycerols, diacylated diols, free fatty acids, cholesterol, and a smaller amount of other polar and nonpolar lipids, whose chemical nature and the very presence in MGS have been a matter of intense debates. The purpose of this review is to discuss recent results that were obtained using different experimental techniques, estimate limitations of their usability, and discuss their biochemical, biophysical, and physiological implications. To create a lipid map of MGS and tears, the results obtained in the author’s laboratory were integrated with available information on chemical composition of MGS and tears. The most informative approaches that are available today to researchers, such as HPLC-MS, GC-MS, and proton NMR, are discussed in details. A map of the meibomian lipidome (as it is seen in reverse phase liquid chromatography/mass spectrometry experiments) is presented. Directions of future efforts in the area are outlined. PMID:23769846

  5. CIDE proteins and lipid metabolism.

    Science.gov (United States)

    Xu, Li; Zhou, Linkang; Li, Peng

    2012-05-01

    Lipid homeostasis is maintained through the coordination of lipid metabolism in various tissues, including adipose tissue and the liver. The disruption of lipid homeostasis often results in the development of metabolic disorders such as obesity, diabetes mellitus, liver steatosis, and cardiovascular diseases. Cell death-inducing DNA fragmentation factor 45-like effector family proteins, including Cidea, Cideb, and Fsp27 (Cidec), are emerging as important regulators of various lipid metabolic pathways and play pivotal roles in the development of metabolic disorders. This review summarizes the latest cell death-inducing DNA fragmentation factor 45-like effector protein discoveries related to the control of lipid metabolism, with emphasis on the role of these proteins in lipid droplet growth in adipocytes and in the regulation of very low-density lipoprotein lipidation and maturation in hepatocytes.

  6. Production of lipids and docosahexasaenoic acid (DHA) by a native Thraustochytrium strain

    DEFF Research Database (Denmark)

    Shene, Carolina; Leyton, Allison; Rubilar, Mónica

    2013-01-01

    conditions for (i) biomass production, (ii) lipid content of the biomass, and (iii) DHA content in the lipids was determined. Taguchi's design of experiments was used to study the influence of two discrete – carbon and nitrogen sources – and six continuous – concentrations of the carbon and nitrogen sources....... In this work the production of DHA by a native Labyrinthulomycetes strain was scaled from shaken flask to a laboratory fermentor with the aid of Taguchi's methodology, process in which biomass concentration, lipid content in the biomass, and DHA content in the lipids were increased....

  7. Polar Lipids of Burkholderia pseudomallei Induce Different Host Immune Responses

    Science.gov (United States)

    Gonzalez-Juarrero, Mercedes; Mima, Naoko; Trunck, Lily A.; Schweizer, Herbert P.; Bowen, Richard A.; Dascher, Kyle; Mwangi, Waithaka; Eckstein, Torsten M.

    2013-01-01

    Melioidosis is a disease in tropical and subtropical regions of the world that is caused by Burkholderia pseudomallei. In endemic regions the disease occurs primarily in humans and goats. In the present study, we used the goat as a model to dissect the polar lipids of B. pseudomallei to identify lipid molecules that could be used for adjuvants/vaccines or as diagnostic tools. We showed that the lipidome of B. pseudomallei and its fractions contain several polar lipids with the capacity to elicit different immune responses in goats, namely rhamnolipids and ornithine lipids which induced IFN-γ, whereas phospholipids and an undefined polar lipid induced strong IL-10 secretion in CD4+ T cells. Autologous T cells co-cultured with caprine dendritic cells (cDCs) and polar lipids of B. pseudomallei proliferated and up-regulated the expression of CD25 (IL-2 receptor) molecules. Furthermore, we demonstrated that polar lipids were able to up-regulate CD1w2 antigen expression in cDCs derived from peripheral blood monocytes. Interestingly, the same polar lipids had only little effect on the expression of MHC class II DR antigens in the same caprine dendritic cells. Finally, antibody blocking of the CD1w2 molecules on cDCs resulted in decreased expression for IFN-γ by CD4+ T cells. Altogether, these results showed that polar lipids of B. pseudomallei are recognized by the caprine immune system and that their recognition is primarily mediated by the CD1 antigen cluster. PMID:24260378

  8. Discovery of MRSA active antibiotics using primary sequence from the human microbiome.

    Science.gov (United States)

    Chu, John; Vila-Farres, Xavier; Inoyama, Daigo; Ternei, Melinda; Cohen, Louis J; Gordon, Emma A; Reddy, Boojala Vijay B; Charlop-Powers, Zachary; Zebroski, Henry A; Gallardo-Macias, Ricardo; Jaskowski, Mark; Satish, Shruthi; Park, Steven; Perlin, David S; Freundlich, Joel S; Brady, Sean F

    2016-12-01

    Here we present a natural product discovery approach, whereby structures are bioinformatically predicted from primary sequence and produced by chemical synthesis (synthetic-bioinformatic natural products, syn-BNPs), circumventing the need for bacterial culture and gene expression. When we applied the approach to nonribosomal peptide synthetase gene clusters from human-associated bacteria, we identified the humimycins. These antibiotics inhibit lipid II flippase and potentiate β-lactam activity against methicillin-resistant Staphylococcus aureus in mice, potentially providing a new treatment regimen.

  9. Amylose-lipid complexes as controlled lipid release agents during starch gelatinization and pasting.

    Science.gov (United States)

    Gelders, Greta G; Goesaert, Hans; Delcour, Jan A

    2006-02-22

    The effect of amylose-lipid (AM-L) complexes consisting of amylose populations with different peak degrees of polymerization (DP) and complexed with glyceryl monostearate (GMS) or docosanoic acid (C22) on the pasting properties of wheat and rice starches was evaluated with a rapid visco analyzer (RVA). AM-L complexes were formed by both (i) addition of lipids to amylose fractions with peak DP 20, 60, 400, or 950 at 60 degrees C or (ii) potato phosphorylase-catalyzed amylose synthesis in the presence of lipids. All AM-L complexes affected pasting properties in line with their dissociation characteristics. AM-L complexes therefore have potential as "controlled lipid release agents" with effects markedly different from those observable with emulsifier addition in starch pasting. More in particular, short chain AM-L complexes resulted in a starch pasting behavior comparable to that of cross-linked starch, as evidenced by reduced granule swelling, good viscosity stability in conditions of high temperature and shear, and a stable cold paste viscosity.

  10. 喹硫平与舒必利治疗Ⅱ型精神分裂症的效果及对患者血脂、血糖代谢影响的对比研究%Comparison of clinical efficacy and effects on blood lipid,glucose metabolism of quetiapine and sulpiride in the treat-ment of type II schizophrenia patients

    Institute of Scientific and Technical Information of China (English)

    王成柱

    2016-01-01

    Objective To compare clinical efficacy and effects on blood lipid,glucose metabolism of quetiapine and sulpiride in the treatment of type II schizophrenia patients. Methods From November 2014 to February 2016 in the Fifth Peo-ple's Hospital of of Kaifeng 60 type II schizophrenia patients were selected,which were randomly divided into quetiapine group and sulpiride group,30 cases in each. Quetiapine group were treated with quetiapine,sulpiride group were treated with sulpiride tablets. Positive and negative symptom scale(PANSS)score,blood lipid level〔total cholesterol(TC),triglyceride(TG), high density lipoprotein cholesterol( HDL - C),low density lipoprotein cholesterol( LDL - C)〕,fasting blood glucose (FBG),glycosylated hemoglobin(HbA1c ),body mass and body mass index(BMI)between the two groups were compared. Results Before and after treatment,PANSS scores between the two groups showed no significant differences(P ﹥ 0. 05). Af-ter the treatment,PANSS score were lower than the before treatment(P ﹤ 0. 05). Before treatment blood lipid level between the two groups showed no significant differences(P ﹥ 0. 05);after treatment TC,TG,LDL - C levels of quetiapine group were lower than sulpiride group and HDL - C was higher than sulpiride group(P ﹤ 0. 05). Before treatment FBG,HbA1c between the two groups showed no significant differences(P ﹥ 0. 05);after treatment FBG,HbA1c of quetiapine group were lower than sulpiride group(P ﹤ 0. 05). Before treatment body weight,BMI between the two groups showed no significant differences(P﹥ 0. 05);after treatment body mass,BMI of quetiapine group were lower than sulpiride group(P ﹤ 0. 05). Conclusion Quetiapine and sulpiride in the treatment of type II schizophrenia can obtain obvious effect,but the effect on the blood lipid, glucose metabolism quetiapine are less.%目的:比较喹硫平与舒必利治疗Ⅱ型精神分裂症的临床效果及对患者血脂、血糖代谢的影响。方法选取2014年11

  11. INFLUÊNCIA DO TEOR DE NITROGÊNIO NO CULTIVO DE Spirulina maxima EM DOIS NÍVEIS DE TEMPERATURA: Parte II: PRODUÇÃO DE LIPÍDIOS INFLUENCE OF THE NITROGEN LEVEL IN THE CULTIVATION OF Spirulina maxima IN TWO LEVELS OF TEMPERATURES: PART II: "PRODUCTION OF LIPIDS"

    Directory of Open Access Journals (Sweden)

    Ricardo Verthein Tavares de MACEDO

    2001-08-01

    Full Text Available A microalga Spirulina maxima foi cultivada em meios com 2,5g/L KNO3 (2,5N, proposto por PAOLETTI et al [10] e considerado meio padrão, em meios com 0,2g/L KNO3 (0,2N e em ausência de nitrogênio (0,0N nas temperaturas de 25°C e 35°C. A composição da biomassa celular seca apresentou a 35°C um aumento médio dos lipídios totais, de 2,8 vezes do meio com ausência de nitrogênio (0,0N e 2,9 vezes do meio 0,2N em relação ao meio padrão. A 25°C apresentou um aumento médio de 3,1 vezes do meio com ausência de nitrogênio (0,0N e 3,2 vezes do meio 0,2N em relação ao meio padrão. A biomassa em forma de gel de cada tratamento foi recolhida e feita a extração dos lipídios totais, os quais foram pesados em base seca. As análises estatísticas dos resultados, em estimativa não linear com superfície de resposta e regressão múltipla com análise de resíduos, mostraram para o aumento dos lipídios totais uma função linear com a temperatura (T e não linear com o nitrogênio (N, ajustando-se a um modelo onde o coeficiente de regressão R=0,99459 e a equação LIPT = A+B²T+CN ².The micraolgae Spirulina maxima was cultivated in medium with 2,5g/L KNO3 (2,5N, proposed by Paoletti et al [10] and considered standard medium, in media with 0,2g/L KNO3 (0,2N and in absence of nitrogen (0,0N in temperatures of 25°C and 35°C. The composition of the dry cellular biomass presented to 35°C a medium increase of the total lipids, of 2,8 times of the middle with absence of nitrogen (0,0N and 2,9 times of the half 0,2N in relation to the standard medium. To 25°C it presented a medium increase of 3,1 times of the medium with absence of nitrogen (0,0N and 3,2 times of the half 0,2N in relation to the standard medium. The biomass in form of gel of each treatment was picked up and made the extraction of the total lipids, which were heavy in base evaporate. The statistical analyses of the results, in estimate non lineal with answer surface and

  12. Lipid nanocarriers: influence of lipids on product development and pharmacokinetics.

    Science.gov (United States)

    Pathak, Kamla; Keshri, Lav; Shah, Mayank

    2011-01-01

    Lipid nanocarriers are on the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery. Owing to their size-dependent properties, lipid nanoparticles offer the possibility for development of new therapeutics and an alternative system to other colloidal counterparts for drug administration. An important point to be considered in the selection of a lipid for the carrier system is its effect on the properties of the nanocarrier and also its intended use, as different types of lipids differ in their nature. Researchers around the globe have tapped the potential of solid lipid nanoparticles (SLNs) in developing formulation(s) that can be administered by various routes such as oral, ocular, parenteral, topical, and pulmonary. Since the start of this millennium, a new generation of lipid nanoparticles, namely nanostructured lipid carriers (NLCs), lipid drug conjugates (LDCs), and pharmacosomes, has evolved that have the potential to overcome the limitations of SLNs. The current review article presents broad considerations on the influence of various types of lipids on the diverse characteristics of nanocarriers, encompassing their physicochemical, formulation, pharmacokinetic, and cytotoxic aspects.

  13. Lipides polaires marins

    OpenAIRE

    Fanni Jacques; Linder Michel; Parmentier Michel

    2004-01-01

    Les lipides polaires marins, notamment les phospholipides (PL), retiennent depuis quelques années l’attention des chercheurs et des industriels en raison de leur composition, particulièrement riche en acides gras polyinsaturés à longue chaîne (AGPI-LC). Ils combinent ainsi les propriétés reconnues des AGPI-LC à l’intérêt métabolique et structural des phospholipides. Les sources sont nombreuses et d’accès très diversifié. Le défi industriel provient de leurs caractéristiques amphiphiles et aro...

  14. Calibrating passive sampling and passive dosing techniques to lipid based concentrations

    DEFF Research Database (Denmark)

    Mayer, Philipp; Schmidt, Stine Nørgaard; Annika, A.;

    2011-01-01

    towards equilibrium partitioning concentrations in lipids (Clipid,partitioning). The first approach proceeds in two steps; (i) the concentration in the PDMS (CPDMS ) is determined and (ii) multiplied with recently determined lipid to PDMS partition ratios (Klipid,PDMS). The second approach applies...... external partitioning standards in vegetable or fish oil for the complete calibration of equilibrium sampling techniques without additional steps. Equilibrium in tissue sampling in three different fish yielded lipid based PCB concentrations in good agreement with those determined using total extraction...... and lipid normalization. These results support the validity of the in tissue sampling technique, while at the same time confirming that the fugacity capacity of these lipid-rich fish tissues for PCBs was dominated by the lipid fraction. Equilibrium sampling of PCB contaminated lake sediments with PDMS...

  15. RF Microalgal lipid content characterization

    Science.gov (United States)

    Ahmad, Mahmoud Al; Al-Zuhair, Sulaiman; Taher, Hanifa; Hilal-Alnaqbi, Ali

    2014-05-01

    Most conventional techniques for the determination of microalgae lipid content are time consuming and in most cases are indirect and require excessive sample preparations. This work presents a new technique that utilizes radio frequency (RF) for rapid lipid quantification, without the need for sample preparation. Tests showed that a shift in the resonance frequency of a RF open-ended coaxial resonator and a gradual increase in its resonance magnitude may occur as the lipids content of microalgae cells increases. These response parameters can be then calibrated against actual cellular lipid contents and used for rapid determination of the cellular lipids. The average duration of lipid quantification using the proposed technique was of about 1 minute, which is significantly less than all other conventional techniques, and was achieved without the need for any time consuming treatment steps.

  16. Chlorosome lipids from Chlorobium tepidum

    DEFF Research Database (Denmark)

    Sørensen, Peder Grove; Cox, Raymond Pickett; Miller, Mette

    2008-01-01

    We have extracted polar lipids and waxes from isolated chlorosomes from the green sulfur bacterium Chlorobium tepidum and determined the fatty acid composition of each lipid class. Polar lipids amounted to 4.8 mol per 100 mol bacteriochlorophyll in the chlorosomes, while non-polar lipids (waxes......) were present at a ratio of 5.9 mol per 100 mol bacteriochlorophyll. Glycolipids constitute 60 % of the polar lipids while phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, and an aminoglycosphingolipid make up respectively 15, 3, 8 and 12 %. A novel glycolipid was identified...... as a rhamnose derivative of monogalactosyldiacylglycerol, while the other major glycolipid was monogalactosyldiacylglycerol. Tetradecanoic acid was the major fatty acid in the aminoglycosphingolipid, while the other polar lipids contained predominantly hexandecanoic acid. The chlorosome waxes are esters...

  17. Texture of lipid bilayer domains

    DEFF Research Database (Denmark)

    Jensen, Uffe Bernchou; Brewer, Jonathan R.; Midtiby, Henrik Skov

    2009-01-01

    chains. By imaging the intensity variations as a function of the polarization angle, we map the lateral variations of the lipid tilt within domains. Results reveal that gel domains are composed of subdomains with different lipid tilt directions. We have applied a Fourier decomposition method......We investigate the texture of gel (g) domains in binary lipid membranes composed of the phospholipids DPPC and DOPC. Lateral organization of lipid bilayer membranes is a topic of fundamental and biological importance. Whereas questions related to size and composition of fluid membrane domain...... are well studied, the possibility of texture in gel domains has so far not been examined. When using polarized light for two-photon excitation of the fluorescent lipid probe Laurdan, the emission intensity is highly sensitive to the angle between the polarization and the tilt orientation of lipid acyl...

  18. Lipids and membrane lateral organization

    Directory of Open Access Journals (Sweden)

    Sandro eSonnino

    2010-11-01

    Full Text Available Shortly after the elucidation of the very basic structure and properties of cellular membranes, it became evident that cellular membranes are highly organized structures with multiple and multi-dimensional levels of order. Very early observations suggested that the lipid components of biological membranes might be active players in the creations of these levels of order. In the late 80’s, several different and diverse experimental pieces of evidence coalesced together giving rise to the lipid raft hypothesis. Lipid rafts became enormously (and, in the opinion of these authors, sometimes acritically popular, surprisingly not just within the lipidologist community (who is supposed to be naturally sensitive to the fascination of lipid rafts. Today, a PubMed search using the key word lipid rafts returned a list of 3767 papers, including 690 reviews (as a term of comparison, searching over the same time span for a very hot lipid-related key word, ceramide returned 6187 hits with 799 reviews, and a tremendous number of different cellular functions have been described as lipid raft-dependent. However, a clear consensus definition of lipid raft has been proposed only in recent times, and the basic properties, the ruling forces, and even the existence of lipid rafts in living cells have been recently matter of intense debate. The scenario that is gradually emerging from the controversies elicited by the lipid raft hypothesis emphasize multiple roles for membrane lipids in determining membrane order, that encompasses their tendency to phase separation but are clearly not limited to this. In this review, we would like to re-focus the attention of the readers on the importance of lipids in organizing the fine structure of cellular membranes.

  19. Absorption Of Dietary Lipid Components

    OpenAIRE

    Abdulkadir Hurşit

    2015-01-01

    Although the digestion and absorption of lipids that are necessary for the survival of living organisms are well known in general terms, nevertheless how different lipids to be digested, how it is distributed into the bloodstream, and how to be used by the cells, are unknown issues by most non specialist people. In recent years, knowledge of lipid digestion and absorption has expanded considerably. More insight has been gained in the mechanism of action of H + pump as a transport system in fa...

  20. Construction of higher-ordered monolayer membranes derived from archaeal membrane lipid-inspired cyclic lipids with longer alkyl chains.

    Science.gov (United States)

    Nakamura, Makoto; Goto, Rie; Tadokoro, Toshio; Shibakami, Motonari

    2007-06-15

    A series of artificial cyclic lipids that mimic archaeal membrane ones has been synthesized. The structural features of these molecules include a longer cyclic framework, in which the alkyl chain length ranges from 24 to 32 in carbon number, which is longer than our first analogous molecule with 20-carbon long alkyl chains [K. Miyawaki, T. Takagi, M. Shibakami, Synlett 8 (2002) 1326]. Microscopic observation reveals that these molecules have a self-assembling ability: hydration of the lipids yields multilamellar vesicles in aqueous solution and monolayer sheets on solid supports. High-sensitivity differential scanning calorimetry (24- and 28-carbon alkyl chain lipids) indicates that (i) the alkyl chain length affects their phase behavior and (ii) the enthalpies of endothermic peaks accompanied by phase transition were considerably lower than those of their monomeric phospholipid analogs. Fluorescence polarization measurements suggest that the membranes made from the 24-carbon alkyl chain lipid have a higher polarization factor than membranes composed of DMPC and DMPC plus cholesterol. These findings imply that the cyclic lipids containing 24- and 28-carbon alkyl chain construct well-organized monolayer membranes and, in particular, that the molecular order of the 24-carbon alkyl chain lipid is higher than that of bilayer membranes in the liquid-ordered phase.

  1. Lipid hydroperoxides in plants.

    Science.gov (United States)

    Griffiths, G; Leverentz, M; Silkowski, H; Gill, N; Sánchez-Serrano, J J

    2000-12-01

    Hydroperoxides are the primary oxygenated products of polyunsaturated fatty acids and were determined spectrophotometrically based on their reaction with an excess of Fe2+ at low pH in the presence of the dye Xylenol Orange. Triphenylphosphine-mediated hydroxide formation was used to authenticate the signal generated by the hydroperoxides. The method readily detected lipid peroxidation in a range of plant tissues including Phaseolus hypocotyls (26 +/- 5 nmol.g of fresh weight(-1); mean +/- S.D.), Alstroemeria floral tissues (sepals, 66+/-13 nmol.g of fresh weight(-1); petals, 49+/-6 nmol.g of fresh weight(-1)), potato leaves (334+/-75 nmol.g of fresh weight(-1)), broccoli florets (568+/-68 nmol.g of fresh weight(-1)) and Chlamydomonas cells (602+/-40 nmol.g of wet weight(-1)). Relative to the total fatty acid content of the tissues, the percentage hydroperoxide content was within the range of 0.6-1.7% for all tissue types (photosynthetic and non-photosynthetic) and represents the basal oxidation level of membrane fatty acids in plant cells. Leaves of transgenic potato with the fatty acid hydroperoxide lyase enzyme expressed in the antisense orientation were elevated by 38%, indicating a role for this enzyme in the maintenance of cellular levels of lipid hydroperoxides.

  2. Phloem proteomics reveals new lipid-binding proteins with a putative role in lipid-mediated signaling

    Directory of Open Access Journals (Sweden)

    Allison Marie Barbaglia

    2016-04-01

    Full Text Available Global climate changes inversely affect our ability to grow the food required for an increasing world population. To combat future crop loss due to abiotic stress, we need to understand the signals responsible for changes in plant development and the resulting adaptations, especially the signaling molecules traveling long-distance through the plant phloem. Using a proteomics approach, we had identified several putative lipid-binding proteins in the phloem exudates. Simultaneously, we identified several complex lipids as well as jasmonates. These findings prompted us to propose that phloem (phospho- lipids could act as long-distance developmental signals in response to abiotic stress, and that they are released, sensed, and moved by phloem lipid-binding proteins (Benning et al., 2012. Indeed, the proteins we identified include lipases that could release a signaling lipid into the phloem, putative receptor components, and proteins that could mediate lipid-movement. To test this possible protein-based lipid-signaling pathway, three of the proteins, which could potentially act in a relay, are characterized here: (I a putative GDSL-motif lipase (II a PIG-P-like protein, with a possible receptor-like function; (III and PLAFP (phloem lipid-associated family protein, a predicted lipid-binding protein of unknown function. Here we show that all three proteins bind lipids, in particular phosphatidic acid (PtdOH, which is known to participate in intracellular stress signaling. Genes encoding these proteins are expressed in the vasculature, a prerequisite for phloem transport. Cellular localization studies show that the proteins are not retained in the endoplasmic reticulum but surround the cell in a spotted pattern that has been previously observed with receptors and plasmodesmatal proteins. Abiotic signals that induce the production of PtdOH also regulate the expression of GDSL-lipase and PLAFP, albeit in opposite patterns. Our findings suggest that while

  3. Update of the LIPID MAPS comprehensive classification system for lipids

    NARCIS (Netherlands)

    Fahy, E.; Subramaniam, S.; Murphy, R.C.; Nishijima, M.; Raetz, C.R.H.; Shimizu, T.; Spener, F.; van Meer, G.; Wakelam, M.J.O.; Dennis, E.A.

    2009-01-01

    In 2005, the International Lipid Classification and Nomenclature Committee under the sponsorship of the LIPID MAPS Consortium developed and established a “Comprehensive Classification System for Lipids” based on well-defined chemical and biochemical principles and using an ontology that is extensibl

  4. Study of antioxidant enzymes, lipid peroxidation, lipid profile and ...

    African Journals Online (AJOL)

    McRoy

    Background: The oxidative stress and inflammation are cooperative events involved in atherosclerosis ... reactive protein (hs-CRP) and lipid status parameters in the patients with coronary artery .... Data were analyzed with t-test and expressed as mean ± SD. ... biomolecules including; lipids, proteins and DNA. Antioxidative ...

  5. Update of the LIPID MAPS comprehensive classification system for lipids

    NARCIS (Netherlands)

    Fahy, E.; Subramaniam, S.; Murphy, R.C.; Nishijima, M.; Raetz, C.R.H.; Shimizu, T.; Spener, F.; van Meer, G.|info:eu-repo/dai/nl/068570368; Wakelam, M.J.O.; Dennis, E.A.

    2009-01-01

    In 2005, the International Lipid Classification and Nomenclature Committee under the sponsorship of the LIPID MAPS Consortium developed and established a “Comprehensive Classification System for Lipids” based on well-defined chemical and biochemical principles and using an ontology that is

  6. Solid lipid nanoparticles for parenteral drug delivery

    NARCIS (Netherlands)

    Wissing, S.A.; Kayser, Oliver; Muller, R.H.

    2004-01-01

    This review describes the use of nanoparticles based on solid lipids for the parenteral application of drugs. Firstly, different types of nanoparticles based on solid lipids such as "solid lipid nanoparticles" (SLN), "nanostructured lipid carriers" (NLC) and "lipid drug conjugate" (LDC) nanoparticle

  7. Solid lipid nanoparticles for parenteral drug delivery

    NARCIS (Netherlands)

    Wissing, S.A.; Kayser, Oliver; Muller, R.H.

    2004-01-01

    This review describes the use of nanoparticles based on solid lipids for the parenteral application of drugs. Firstly, different types of nanoparticles based on solid lipids such as "solid lipid nanoparticles" (SLN), "nanostructured lipid carriers" (NLC) and "lipid drug conjugate" (LDC)

  8. Building a multilevel modeling network for lipid processing systems

    DEFF Research Database (Denmark)

    Mustaffa, Azizul Azri; Díaz Tovar, Carlos Axel; Hukkerikar, Amol

    2011-01-01

    data collected from existing process plants, and application of validated models in design and analysis of unit operations; iv) the information and models developed are used as building blocks in the development of methods and tools for computer-aided synthesis and design of process flowsheets (CAFD......The aim of this work is to present the development of a computer aided multilevel modeling network for the systematic design and analysis of processes employing lipid technologies. This is achieved by decomposing the problem into four levels of modeling: i) pure component property modeling...... and a lipid-database of collected experimental data from industry and generated data from validated predictive property models, as well as modeling tools for fast adoption-analysis of property prediction models; ii) modeling of phase behavior of relevant lipid mixtures using the UNIFAC-CI model, development...

  9. Lipid Processing Technology: Building a Multilevel Modeling Network

    DEFF Research Database (Denmark)

    Díaz Tovar, Carlos Axel; Mustaffa, Azizul Azri; Mukkerikar, Amol

    2011-01-01

    in design and analysis of unit operations; iv) the information and models developed are used as building blocks in the development of methods and tools for computer-aided synthesis and design of process flowsheets (CAFD). The applicability of this methodology is highlighted in each level of modeling through......The aim of this work is to present the development of a computer aided multilevel modeling network for the systematic design and analysis of processes employing lipid technologies. This is achieved by decomposing the problem into four levels of modeling: i) pure component property modeling...... and a lipid-database of collected experimental data from industry and generated data from validated predictive property models, as well as modeling tools for fast adoption-analysis of property prediction models; ii) modeling of phase behavior of relevant lipid mixtures using the UNIFACCI model, development...

  10. Lipid peroxidation of rabbit small intestinal microvillus membrane vesicles by iron complexes.

    Science.gov (United States)

    Fodor, I; Marx, J J

    1988-07-01

    Fe(II)- and Fe(III)-induced lipid peroxidation of rabbit small intestinal microvillus membrane vesicles was studied. Ferrous ammonium sulphate, ferrous ascorbate at a molar ratio of 10:1, and ferric citrate, at molar ratios of 1:1 and 1:20, did not stimulate lipid peroxidation. Ferrous ascorbate, 1:1, induced low stimulation, while ferrous ascorbate, 1:20 gave higher stimulation of lipid peroxidation. These results show that in our experimental system, ascorbate is a promotor rather than an inhibitor of lipid peroxidation. Ferric nitrilotriacetate (at molar ratios of 1:2 and 1:10), at an iron concentration of 200 microM, was by far the most effective in inducing lipid peroxidation. Superoxide dismutase, mannitol and glutathione had no effect, while catalase, thiourea and vitamin E markedly decreased ferrous ascorbate 1:20-induced lipid peroxidation. Ferric nitrilotriacetate-induced lipid peroxidation was slightly reduced by catalase and mannitol, significantly reduced by superoxide dismutase, and completely inhibited by thiourea. Glutathione caused a 100% increase in the ferric nitrilotriacetate-induced lipid peroxidation. These results suggest that Fe(II) in the presence of trace amounts of Fe(III), or an oxidizing agent and Fe(III) in the presence of Fe(II) or a reducing agent, are potent stimulators of lipid peroxidation of microvillus membrane vesicles. Addition of deferoxamine completely inhibited both ferrous ascorbate, 1:20 and ferric nitrilotriacetate-induced lipid peroxidation, demonstrating the requirement for iron for its stimulation. Iron-induced peroxidation of microvillus membrane may have physiological significance because it could already be demonstrated at 2 microM iron concentration.

  11. Molecular Dynamics of Lipid Bilayers

    Science.gov (United States)

    1989-08-09

    The aim of this work is to study, by molecular dynamics simulations, the properties of lipid bilayers. We have applied the vectorizable, order-N...fast angle-dependent force/potential algorithms to treat angle bending and torsion. Keywords: Molecular dynamics , Lipid bilayers.

  12. Fasting and nonfasting lipid levels

    DEFF Research Database (Denmark)

    Langsted, Anne; Freiberg, Jacob J; Nordestgaard, Børge G

    2008-01-01

    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.......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....

  13. Fasting and nonfasting lipid levels

    DEFF Research Database (Denmark)

    Langsted, Anne; Freiberg, Jacob J; Nordestgaard, Børge G

    2008-01-01

    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.......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....

  14. Lipid droplets, lipophagy, and beyond.

    Science.gov (United States)

    Wang, Chao-Wen

    2016-08-01

    Lipids are essential components for life. Their various structural and physical properties influence diverse cellular processes and, thereby, human health. Lipids are not genetically encoded but are synthesized and modified by complex metabolic pathways, supplying energy, membranes, signaling molecules, and hormones to affect growth, physiology, and response to environmental insults. Lipid homeostasis is crucial, such that excess fatty acids (FAs) can be harmful to cells. To prevent such lipotoxicity, cells convert excess FAs into neutral lipids for storage in organelles called lipid droplets (LDs). These organelles do not simply manage lipid storage and metabolism but also are involved in protein quality management, pathogenesis, immune responses, and, potentially, neurodegeneration. In recent years, a major trend in LD biology has centered around the physiology of lipid mobilization via lipophagy of fat stored within LDs. This review summarizes key findings in LD biology and lipophagy, offering novel insights into this rapidly growing field. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.

  15. Roles of Lipids in Photosynthesis.

    Science.gov (United States)

    Kobayashi, Koichi; Endo, Kaichiro; Wada, Hajime

    2016-01-01

    Thylakoid membranes in cyanobacterial cells and chloroplasts of algae and higher plants are the sites of oxygenic photosynthesis. The lipid composition of the thylakoid membrane is unique and highly conserved among oxygenic photosynthetic organisms. Major lipids in thylakoid membranes are glycolipids, monogalactosyldiacylglycerol, digalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol, and the phospholipid, phosphatidylglycerol. The identification of almost all genes involved in the biosynthesis of each lipid class over the past decade has allowed the generation and isolation of mutants of various photosynthetic organisms incapable of synthesizing specific lipids. Numerous studies using such mutants have revealed that these lipids play important roles not only in the formation of the lipid bilayers of thylakoid membranes but also in the folding and assembly of the protein subunits in photosynthetic complexes. In addition to the studies with the mutants, recent X-ray crystallography studies of photosynthetic complexes in thylakoid membranes have also provided critical information on the association of lipids with photosynthetic complexes and their activities. In this chapter, we summarize our current understanding about the structural and functional involvement of thylakoid lipids in oxygenic photosynthesis.

  16. The Flexibility of Ectopic Lipids

    Directory of Open Access Journals (Sweden)

    Hannah Loher

    2016-09-01

    Full Text Available In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL, skeletal (intramyocellular lipids; IMCL or cardiac muscle cells (intracardiomyocellular lipids; ICCL. Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. 1H-magnetic resonance spectroscopy (1H-MRS is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass, insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations.

  17. Neuroimaging of Lipid Storage Disorders

    Science.gov (United States)

    Rieger, Deborah; Auerbach, Sarah; Robinson, Paul; Gropman, Andrea

    2013-01-01

    Lipid storage diseases, also known as the lipidoses, are a group of inherited metabolic disorders in which there is lipid accumulation in various cell types, including the central nervous system, because of the deficiency of a variety of enzymes. Over time, excessive storage can cause permanent cellular and tissue damage. The brain is particularly…

  18. The Flexibility of Ectopic Lipids.

    Science.gov (United States)

    Loher, Hannah; Kreis, Roland; Boesch, Chris; Christ, Emanuel

    2016-09-14

    In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL), skeletal (intramyocellular lipids; IMCL) or cardiac muscle cells (intracardiomyocellular lipids; ICCL). Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. ¹H-magnetic resonance spectroscopy (¹H-MRS) is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass), insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term) appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations.

  19. Lipides polaires marins

    Directory of Open Access Journals (Sweden)

    Fanni Jacques

    2004-03-01

    Full Text Available Les lipides polaires marins, notamment les phospholipides (PL, retiennent depuis quelques années l’attention des chercheurs et des industriels en raison de leur composition, particulièrement riche en acides gras polyinsaturés à longue chaîne (AGPI-LC. Ils combinent ainsi les propriétés reconnues des AGPI-LC à l’intérêt métabolique et structural des phospholipides. Les sources sont nombreuses et d’accès très diversifié. Le défi industriel provient de leurs caractéristiques amphiphiles et aromatiques particulièrement marquées qui rend leur extraction très difficile.

  20. Lipid functionalized biopolymers: A review.

    Science.gov (United States)

    Qurat-Ul-Ain; Zia, Khalid Mahmood; Zia, Fatima; Ali, Muhammad; Rehman, Saima; Zuber, Mohammad

    2016-12-01

    Lipids are the main source of energy and widely used for various applications. In this review, the modification of lipids by using them in combination with other biomaterials like natural and synthetic polymers is elaborated. These new blends have characteristic features of both polymers and are characterized by different techniques (NMR, DSC, TGA, IR and Raman spectroscopy etc.) to understand their structure, properties and functional behavior. Lipids are hydrophobic, have anti-oxidant and anti-bacterial properties and thus impart hydrophobicity and flexibility to the polymers. While the polymers, on the other hand, make the lipids tougher. Properties of few polymers such as starch, polyethylene protein and chitosan that have brittleness, low combustion rate and hydrophobicity, are improved by incorporation of lipids ultimately increased their flexibility, combustion rate and hydrophobicity respectively. This review article is also focused on emerging fields for the applications of these composite materials. The most notable application of composite materials are in the field of paint industry.

  1. Lipids changes in liver cancer

    Institute of Scientific and Technical Information of China (English)

    JIANG Jing-ting; XU Ning; ZHANG Xiao-ying; WU Chang-ping

    2007-01-01

    Liver is one of the most important organs in energy metabolism.Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver.It depends on the integrity of liver cellular function,which ensures homeostasis of lipid and lipoprotein metabolism.When liver cancer occurs,these processes are impaired and the plasma lipid and lipoprotein patterns may be changed.Liver cancer is the fifth common malignant tumor worldwide,and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV).HBV and HCV infections are quite common in China and other Southeast Asian countries.In addition,liver cancer is often followed by a procession of chronic hepatitis or cirrhosis,so that hepatic function is damaged obviously on these bases,which may significantly influence lipid and lipoprotein metabolism in vivo.In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer.

  2. Lipid traffic: the ABC of transbilayer movement

    NARCIS (Netherlands)

    Raggers, R.J.; Pomorski, T.; Holthuis, J.C.M.; Kälin, N.; van Meer, G.

    2000-01-01

    Membrane lipids do not spontaneously exchange between the two leaflets of lipid bilayers because the polar headgroups cannot cross the hydrophobic membrane interior. Cellular membranes, notably eukaryotic plasma membranes, are equipped with special proteins that actively translocate lipids from one

  3. Mineralization of annexin-5-containing lipid-calcium-phosphate complexes: modulation by varying lipid composition and incubation with cartilage collagens.

    Science.gov (United States)

    Genge, Brian R; Wu, Licia N Y; Wuthier, Roy E

    2008-04-11

    Matrix vesicles (MVs) in the growth plate bind to cartilage collagens and initiate mineralization of the extracellular matrix. Native MVs have been shown to contain a nucleational core responsible for mineral formation that is comprised of Mg(2+)-containing amorphous calcium phosphate and lipid-calcium-phosphate complexes (CPLXs) and the lipid-dependent Ca(2+)-binding proteins, especially annexin-5 (Anx-5), which greatly enhances mineral formation. Incorporation of non-Ca(2+)-binding MV lipids impedes mineral formation by phosphatidylserine (PS)-CPLX. In this study, nucleators based on amorphous calcium phosphate (with or without Anx-5) were prepared with PS alone, PS + phosphatidylethanolamine (PE), or PS + PE and other MV lipids. These were incubated in synthetic cartilage lymph containing no collagen or containing type II or type X collagen. Dilution of PS with PE and other MV lipids progressively retarded nucleation. Incorporation of Anx-5 restored nucleational activity to the PS:PE CPLX; thus PS and Anx-5 proved to be critical for nucleation of mineral. Without Anx-5, induction of mineral formation was slow unless high levels of Ca(2+) were used. The presence of type II collagen in synthetic cartilage lymph improved both the rate and amount of mineral formation but did not enhance nucleation. This stimulatory effect required the presence of the nonhelical telopeptides. Although type X collagen slowed induction, it also increased the rate and amount of mineral formation. Both type II and X collagens markedly increased mineral formation by the MV-like CPLX, requiring Anx-5 to do so. Thus, Anx-5 enhances nucleation by the CPLXs and couples this to propagation of mineral formation by the cartilage collagens.

  4. SOLID LIPID NANOPARTICLES AND NANO LIPID CARRIERS: AS NOVEL SOLID LIPID BASED DRUG CARRIER

    Directory of Open Access Journals (Sweden)

    Girish B. Singhal

    2011-02-01

    Full Text Available Interest in lipid based drug delivery has developed over the past decade fuelled by a better understanding of the multiple roles lipids may play in enhancing oral bioavailability. Moreover, the emergence of novel excipients with acceptable regulatory and safety profiles coupled with advances in formulation technologies have greatly improved the potential for successful lipid based formulations. Solid lipid nanoparticles (SLN introduced in 1991 represent an alternative carrier system to traditional colloidal carriers, such as emulsions, liposomes and polymeric micro- and nanoparticles. SLN combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews the present state of the art regarding production techniques for SLN/ nanostructured lipid carrier (NLC, drug incorporation method and types, stability. The potential of SLN/NLC to be exploited for the different administration routes is also highlighted.

  5. Physiological Roles for mafr-1 in Reproduction and Lipid Homeostasis

    Directory of Open Access Journals (Sweden)

    Akshat Khanna

    2014-12-01

    Full Text Available Maf1 is a conserved repressor of RNA polymerase (Pol III transcription; however, its physiological role in the context of a multicellular organism is not well understood. Here, we show that C. elegans MAFR-1 is functionally orthologous to human Maf1, represses the expression of both RNA Pol III and Pol II transcripts, and mediates organismal fecundity and lipid homeostasis. MAFR-1 impacts lipid transport by modulating intestinal expression of the vitellogenin family of proteins, resulting in cell-nonautonomous defects in the developing reproductive system. MAFR-1 levels inversely correlate with stored intestinal lipids, in part by influencing the expression of the lipogenesis enzymes fasn-1/FASN and pod-2/ACC1. Animals fed a high carbohydrate diet exhibit reduced mafr-1 expression and mutations in the insulin signaling pathway genes daf-18/PTEN and daf-16/FoxO abrogate the lipid storage defects associated with deregulated mafr-1 expression. Our results reveal physiological roles for mafr-1 in regulating organismal lipid homeostasis, which ensure reproductive success.

  6. Lipid peroxidation and antioxidant enzymes in male infertility.

    Directory of Open Access Journals (Sweden)

    Dandekar S

    2002-07-01

    Full Text Available BACKGROUND AND AIM: Mammalian spermatozoa are rich in polyunsaturated fatty acids and are very susceptible to attack by reactive oxygen species (ROS and membrane lipid peroxide ion. Normally a balance is maintained between the amount of ROS produced and that scavenged. Cellular damage arises when this equilibrium is disturbed. A shift in the levels of ROS towards pro-oxidants in semen and vaginal secretions can induce an oxidative stress on spermatozoa. The aim was to study lipid peroxidation and antioxidant enzymes such as catalase, glutathione peroxidase and superoxide dismutase (SOD and to correlate the same, with the ′water test′, in male infertility. SETTINGS: Experimental study. SUBJECTS AND METHODS: Ejaculates from a total of 83 infertile and fertile healthy individuals were obtained. Lipid peroxidation and antioxidant enzyme levels were studied and correlated with water test. RESULTS: The results indicate that (i the antioxidant enzyme catalase showed no significant changes in the various pathological samples, (ii antioxidant enzymes SOD and glutathione peroxidase correlate positively with asthenozoospermic samples and (iii the degree of lipid peroxidation also correlates positively with the poorly swollen sperm tails. The increase in SOD and glutathione peroxidase values, in the pathological cases represents an attempt made to overcome the reactive oxygen species. CONCLUSION: Water test could be used as a preliminary marker test for sperm tail damage by reactive oxygen species, since it correlates very well with lipid peroxidation and antioxidant enzymes.

  7. Disorders of muscle lipid metabolism: diagnostic and therapeutic challenges.

    Science.gov (United States)

    Laforêt, Pascal; Vianey-Saban, Christine

    2010-11-01

    Disorders of muscle lipid metabolism may involve intramyocellular triglyceride degradation, carnitine uptake, long-chain fatty acids mitochondrial transport, or fatty acid β-oxidation. Three main diseases leading to permanent muscle weakness are associated with severe increased muscle lipid content (lipid storage myopathies): primary carnitine deficiency, neutral lipid storage disease and multiple acyl-CoA dehydrogenase deficiency. A moderate lipidosis may be observed in fatty acid oxidation disorders revealed by rhabdomyolysis episodes such as carnitine palmitoyl transferase II, very-long-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein deficiencies, and in recently described phosphatidic acid phosphatase deficiency. Respiratory chain disorders and congenital myasthenic syndromes may also be misdiagnosed as fatty acid oxidation disorders due to the presence of secondary muscle lipidosis. The main biochemical tests giving clues for the diagnosis of these various disorders are measurements of blood carnitine and acylcarnitines, urinary organic acid profile, and search for intracytoplasmic lipid on peripheral blood smear (Jordan's anomaly). Genetic analysis orientated by the results of biochemical investigation allows establishing a firm diagnosis. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency may be treated after supplementation with carnitine, riboflavine and coenzyme Q10. New therapeutic approaches for fatty acid oxidation disorders are currently developed, based on pharmacological treatment with bezafibrate, and specific diets enriched in medium-chain triglycerides or triheptanoin.

  8. Targeting proteins to liquid-ordered domains in lipid membranes.

    Science.gov (United States)

    Stachowiak, Jeanne C; Hayden, Carl C; Sanchez, Mari Angelica A; Wang, Julia; Bunker, Bruce C; Voigt, James A; Sasaki, Darryl Y

    2011-02-15

    We demonstrate the construction of novel protein-lipid assemblies through the design of a lipid-like molecule, DPIDA, endowed with tail-driven affinity for specific lipid membrane phases and head-driven affinity for specific proteins. In studies performed on giant unilamellar vesicles (GUVs) with varying mole fractions of dipalymitoylphosphatidylcholine (DPPC), cholesterol, and diphytanoylphosphatidyl choline (DPhPC), DPIDA selectively partitioned into the more ordered phases, either solid or liquid-ordered (L(o)) depending on membrane composition. Fluorescence imaging established the phase behavior of the resulting quaternary lipid system. Fluorescence correlation spectroscopy confirmed the fluidity of the L(o) phase containing DPIDA. In the presence of CuCl(2), the iminodiacetic acid (IDA) headgroup of DPIDA forms the Cu(II)-IDA complex that exhibits a high affinity for histidine residues. His-tagged proteins were bound specifically to domains enriched in DPIDA, demonstrating the capacity to target protein binding selectively to both solid and L(o) phases. Steric pressure from the crowding of surface-bound proteins transformed the domains into tubules with persistence lengths that depended on the phase state of the lipid domains.

  9. Lipid composition of human meibum

    Directory of Open Access Journals (Sweden)

    R. Schnetler

    2013-12-01

    Full Text Available The structure and function of meibomian gland lipids in the tear film are highly complex. Evidence shows that the precorneal tear film consists of discrete layers: the inner mucin layer, the middle aqueous layer and the outer lipid layer. In this review we focus on the outer, biphasic lipid layer of the tear film which consists of a ‘thick’ outer, non-polar layer  and a ‘thin’ inner, polar layer. We discuss the main composition of the polar and non-polar lipids within meibum (wax esters, cholesteryl esters, mono-, di- and tri-acylglycerols, ceramides, phospholipids  et cetera. We address the composition of meibomian lipids in subjects suffering from various ocular diseases in comparison with the composition in healthy individuals. Further analysis is needed to determine whether a correlation exists between the etiology of various ocular diseases and the fluctuation on the lipids as well as to establish whether or not tear lipid analysis can be used as a diagnostic tool.

  10. Monte Carlo study of receptor-lipid raft formation on a cell membrane

    Science.gov (United States)

    Yu-Yang, Paul; Srinivas Reddy, A.; Raychaudhuri, Subhadip

    2012-02-01

    Receptors are cell surface molecules that bind with extracellular ligand molecules leading to propagation of downstream signals and cellular activation. Even though ligand binding-induced formation of receptor-lipid rafts has been implicated in such a process, the formation mechanism of such large stable rafts is not understood. We present findings from our Monte Carlo (MC) simulations involving (i) receptor interaction with the membrane lipids and (ii) lipid-lipid interactions between raft forming lipids. We have developed a hybrid MC simulation method that combines a probabilistic MC simulation with an explicit free energy-based MC scheme. Some of the lipid-mediated interactions, such as the cholesterol-lipid interactions, are simulated in an implicit way. We examine the effect of varying attractive interactions between raft forming lipids and ligand-bound receptors and show that strong coupling between receptor-receptor and receptor-sphingolipid molecules generate raft formation similar to that observed in recent biological experiments. We study the effect of variation of receptor affinity for ligands (as happens in adaptive immune cells) on raft formation. Such affinity dependence in receptor-lipid raft formation provides insight into important problems in B cell biology.

  11. Partitioning of hydrophobic organic contaminants between polymer and lipids for two silicones and low density polyethylene.

    Science.gov (United States)

    Smedes, Foppe; Rusina, Tatsiana P; Beeltje, Henry; Mayer, Philipp

    2017-08-11

    Polymers are increasingly used for passive sampling of neutral hydrophobic organic substances (HOC) in environmental media including water, air, soil, sediment and even biological tissue. The equilibrium concentration of HOC in the polymer can be measured and then converted into equilibrium concentrations in other (defined) media, which however requires appropriate polymer to media partition coefficients. We determined thus polymer-lipid partition coefficients (KPL) of various PCB, PAH and organochlorine pesticides by equilibration of two silicones and low density polyethylene (LDPE) with fish oil and Triolein at 4 °C and 20 °C. We observed (i) that KPL was largely independent of lipid type and temperature, (ii) that lipid diffusion rates in the polymers were higher compared to predictions based on their molecular volume, (iii) that silicones showed higher lipid diffusion and lower lipid sorption compared to LDPE and (iv) that absorbed lipid behaved like a co-solute and did not affect the partitioning of HOC at least for the smaller molecular size HOC. The obtained KPL can convert measured equilibrium concentrations in passive sampling polymers into equilibrium concentrations in lipid, which then can be used (1) for environmental quality monitoring and assessment, (2) for thermodynamic exposure assessment and (3) for assessing the linkage between passive sampling and the traditionally measured lipid-normalized concentrations in biota. LDPE-lipid partition coefficients may also be of use for a thermodynamically sound risk assessment of HOC contained in microplastics. Copyright © 2017. Published by Elsevier Ltd.

  12. Lipid peroxidation and water penetration in lipid bilayers

    DEFF Research Database (Denmark)

    Conte, Elena; Megli, Francesco Maria; Khandelia, Himanshu

    2012-01-01

    Lipid peroxidation plays a key role in the alteration of cell membrane's properties. Here we used as model systems multilamellar vesicles (MLVs) made of the first two products in the oxidative cascade of linoleoyl lecithin, namely 1-palmitoyl-2-(13-hydroperoxy-9,11-octadecanedienoyl)-lecithin (Hp......PLPC) and 1-palmitoyl-2-(13-hydroxy-9,11-octadecanedienoyl)-lecithin (OHPLPC), exhibiting a hydroperoxide or a hydroxy group at position 13, respectively. The two oxidized lipids were used either pure or in a 1:1 molar ratio mixture with untreated 1-palmitoyl-2-linoleoyl-lecithin (PLPC). The model membranes...... were doped with spin-labeled lipids to study bilayer alterations by electron paramagnetic resonance (EPR) spectroscopy. Two different spin-labeled lipids were used, bearing the doxyl ring at position (n) 5 or 16: γ-palmitoyl-β-(n-doxylstearoyl)-lecithin (n-DSPPC) and n-doxylstearic acid (n-DSA). Small...

  13. Assessment of lipid metabolism in thyroid dysfunction

    Directory of Open Access Journals (Sweden)

    V. G. Kadzharyan

    2014-02-01

    Full Text Available 1. Actuality According to WHO Thyroid dysfunction is one of the most prevalent in humans and is one of the risk factors of cardiovascular diseases. Hypothyroidism affects the mechanisms of potentiation of cardiovascular risk factors, suggesting the need to study the level of the blood lipids in all patients with thyroid dysfunction. 2. The purpose of this study. To define features of lipid metabolism, depending on the functional state of the thyroid gland. 3. Material and methods. The study included 95 patients, mean age was 49,8 ± 12,9 years. 74 of them were women (78% and 21 - men (22%. In accordance with the purpose of the work 3 groups of subjects were formed. I-st group - 35 patients with hypothyroidism, mean age 52,5 ± 10,3 years, II-nd group - 37 patients with hyperthyroidism, the average age was 45,1 ± 13 years, III (control group - 23 patients with euthyroid, mean age 53,9 ± 14,8 years. Levels of TSH, triiodothyronine, thyroxine, microsomal antibodies to thyroglobulin and thyroid peroxidase were evaluated for total and biochemical analysis. To determine the type of hyperlipoproteinemia Fredrickson, 1967 recommendations were used. 4. Results of the study Lipid profile parameters in the I-st group compared with the control were even higher. Cholesterol increased up to 6,9% (p <0,005, Tg - 8,6% (p <0,005, β -DP - 6,8% (p <0,5, in comparison with the II-nd: cholesterol - 56% (p <0,005, TG - 55% (p <0,005 and β-PL 44% (p <0.5. In group II rates were lower than in the III- cholesterol - 8% (p <0,005, Tg 8,3% (p <0,005 and β-PL 6,5% (p <0,5. Patients from the I-st group had the following distribution of hyperlipidemia (Fredrickson, 1967.: I type - 10 patients (29%; IIb type - 15 subjects (43%; IIa type - 9 subjects (26%; IV type - 1 patient (2%. The correlation dependence of TSH and cholesterol (r = +0,37, p <0,05, TG (r = +0,25, p <0,05, β-PL (r = +0,74, p <0.05, TG AT (r = +0,55, p <0,05, the level of bilirubin (r = +0,29, p <0

  14. Pb II

    African Journals Online (AJOL)

    Windows User

    ISSN 1684–5315 ©2012 Academic Journals ... Exposure to Pb above permissible limit (50 ppb in water) .... taken and analyzed for residual metal concentration determination. ..... loss in Pb(II) sorption capacity up to five cycles of reuse of.

  15. Container II

    OpenAIRE

    Baraklianou, Stella

    2016-01-01

    Container II, self-published artists book.\\ud The book was made on the occasion of the artists residency at the Banff Arts Centre, in Alberta Canada. \\ud \\ud Container II is a performative piece, it worked in conjunction with the photographic installation "Stage Set: Cool Tone" . (photographic floor installation, Reclaimed wood, frames, 130x145cm, 2016) \\ud The photographic installation was also part of the artists residency titled "New Materiality" at the Banff Arts Centre. \\ud \\ud Limited E...

  16. Dietary lipids and cancer.

    Science.gov (United States)

    Granados, S; Quiles, J L; Gil, A; Ramírez-Tortosa, M C

    2006-05-01

    Cancer is one of the main causes of death in Western countries. Among the factors that contribute to the appearance of this disease, diet has a fundamental role, and specifically fats are the main component related to the increase in the incidence of cancerous diseases, particularly breast, colon-rectal, and prostate cancer. From dietary lipids, much attention has been given to the beneficial effects of fish oil, rich in polyunsaturated fatty acids n-3 serie, as well as of olive oil, rich in monounsaturated fatty acids--primarily oleic acid. On the contrary, a negative effect has been reported for polyunsaturated fatty acids n-6 serie and for saturated fatty acids. Nutrition constitutes an important aspect of the life of cancer patients. Currently, nutritional formulas are being designed with supplements of polyunsaturated n-3 fatty acids and other components such as arginine, RNA, lysine, etc., with the aim of ameliorating the effects of this pathology. The results demonstrate the lower morbility and therefore improved quality of life, a decline in mortality, and a reduction in related costs.

  17. Hybrid lipid-based nanostructures

    Science.gov (United States)

    Dayani, Yasaman

    Biological membranes serve several important roles, such as structural support of cells and organelles, regulation of ionic and molecular transport, barriers to non-mediated transport, contact between cells within tissues, and accommodation of membrane proteins. Membrane proteins and other vital biomolecules incorporated into the membrane need a lipid membrane to function. Due to importance of lipid bilayers and their vital function in governing many processes in the cell, the development of various models as artificial lipid membranes that can mimic cell membranes has become a subject of great interest. Using different models of artificial lipid membranes, such as liposomes, planar lipid bilayers and supported or tethered lipid bilayers, we are able to study many biophysical processes in biological membranes. The ability of different molecules to interact with and change the structure of lipid membranes can be also investigated in artificial lipid membranes. An important application of lipid bilayer-containing interfaces is characterization of novel membrane proteins for high throughput drug screening studies to investigate receptor-drug interactions and develop biosensor systems. Membrane proteins need a lipid bilayer environment to preserve their stability and functionality. Fabrication of materials that can interact with biomolecules like proteins necessitates the use of lipid bilayers as a mimic of cell membranes. The objective of this research is to develop novel hybrid lipid-based nanostructures mimicking biological membranes. Toward this aim, two hybrid biocompatible structures are introduced: lipid bilayer-coated multi-walled carbon nanotubes (MWCNTs) and hydrogel-anchored liposomes with double-stranded DNA anchors. These structures have potential applications in biosensing, drug targeting, drug delivery, and biophysical studies of cell membranes. In the first developed nanostructure, lipid molecules are covalently attached to the surfaces of MWCNTs, and

  18. Analysis of Lipid Experiments (ALEX)

    DEFF Research Database (Denmark)

    Husen, Peter; Tarasov, Kirill; Katafiasz, Maciej

    2013-01-01

    Global lipidomics analysis across large sample sizes produces high-content datasets that require dedicated software tools supporting lipid identification and quantification, efficient data management and lipidome visualization. Here we present a novel software-based platform for streamlined data ...

  19. SOLID LIPID NANOPARTICLES: A REVIEW

    Directory of Open Access Journals (Sweden)

    Mudavath Hanumanaik*, Sandeep Kumar Patel and K. Ramya Sree

    2013-03-01

    Full Text Available ABSTRACT: Solid lipid nanoparticles (SLN are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery and research. Due to their unique size dependent properties, lipid nanoparticles offer possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could use for drug targeting. Hence solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery and hence attracted wide attention of researchers. This review presents a broad treatment of solid lipid nanoparticles discussing their aims, production procedures, advantages, limitations and their possible remedies. Appropriate analytical techniques for the characterization of SLN like Photon Correlation Spectroscopy (PCS, Scanning Electron Microscopy (SEM, and Differential Scanning Calorimetry are highlighted. Aspects of SLN route of administration and the in vivo fate of the carriers are also discussed.

  20. Electronic polymers in lipid membranes.

    Science.gov (United States)

    Johansson, Patrik K; Jullesson, David; Elfwing, Anders; Liin, Sara I; Musumeci, Chiara; Zeglio, Erica; Elinder, Fredrik; Solin, Niclas; Inganäs, Olle

    2015-06-10

    Electrical interfaces between biological cells and man-made electrical devices exist in many forms, but it remains a challenge to bridge the different mechanical and chemical environments of electronic conductors (metals, semiconductors) and biosystems. Here we demonstrate soft electrical interfaces, by integrating the metallic polymer PEDOT-S into lipid membranes. By preparing complexes between alkyl-ammonium salts and PEDOT-S we were able to integrate PEDOT-S into both liposomes and in lipid bilayers on solid surfaces. This is a step towards efficient electronic conduction within lipid membranes. We also demonstrate that the PEDOT-S@alkyl-ammonium:lipid hybrid structures created in this work affect ion channels in the membrane of Xenopus oocytes, which shows the possibility to access and control cell membrane structures with conductive polyelectrolytes.

  1. Lipid dynamics at dendritic spines.

    Science.gov (United States)

    Dotti, Carlos Gerardo; Esteban, Jose Antonio; Ledesma, María Dolores

    2014-01-01

    Dynamic changes in the structure and composition of the membrane protrusions forming dendritic spines underlie memory and learning processes. In recent years a great effort has been made to characterize in detail the protein machinery that controls spine plasticity. However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants. Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling. In this review we gather information available on the lipid composition at dendritic spine membranes and on its dynamics. We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

  2. An Overview of Lipid Droplets in Cancer and Cancer Stem Cells

    KAUST Repository

    Tirinato, Luca

    2017-08-13

    For decades, lipid droplets have been considered as the main cellular organelles involved in the fat storage, because of their lipid composition. However, in recent years, some new and totally unexpected roles have been discovered for them: (i) they are active sites for synthesis and storage of inflammatory mediators, and (ii) they are key players in cancer cells and tissues, especially in cancer stem cells. In this review, we summarize the main concepts related to the lipid droplet structure and function and their involvement in inflammatory and cancer processes.

  3. A new look at lipid-membrane structure in relation to drug research

    DEFF Research Database (Denmark)

    Mouritsen, Ole G.; Jørgensen, Kent

    1998-01-01

    Lipid-bilayer membranes are key objects in drug research in relation to (i) interaction of drugs with membrane-bound receptors, (ii) drug targeting, penetration, and permeation of cell membranes, and (iii) use of liposomes in micro-encapsulation technologies for drug delivery. Rational design...... of new drugs and drug-delivery systems therefore requries insight into the physical properties of lipid-bilayer membranes. This mini-review provides a perspective on the current view of lipid-bilayer structure and dynamics based on information obtained from a variety of recent experimental...

  4. Mealworms: Alternate Source of Lipids

    OpenAIRE

    2014-01-01

    The aim of present study was to determine the physicochemical properties of the oil obtained from Tenebrio molitor larvae (mealworms) and explore its potential as edible oil. Five batches of Tenebrio molitor larvae were investigated for their lipid content and physiochemical properties. Three batches were reared in lab (3 different productions) and two were purchased from a local supplier. The lipids were extracted using a cold extraction technique employing 2:1 ratio chloroform/methanol as s...

  5. NMR spectroscopy for evaluation of lipid oxidation

    Science.gov (United States)

    During storage and use of edible oils and other lipid-containing foods, reactions between lipids and oxygen occur, resulting in lipid oxidation and the subsequent development of off-flavors and odors. Accurate and timely assessment of lipid oxidation is critical for effective quality control of food...

  6. Scavenger receptor AI/II truncation, lung function and COPD: a large population-based study

    DEFF Research Database (Denmark)

    Thomsen, M; Nordestgaard, B G; Tybjærg-Hansen, Anne

    2011-01-01

    The scavenger receptor A-I/II (SRA-I/II) on alveolar macrophages is involved in recognition and clearance of modified lipids and inhaled particulates. A rare variant of the SRA-I/II gene, Arg293X, truncates the distal collagen-like domain, which is essential for ligand recognition. We tested whet...

  7. Phase structure of liposome in lipid mixtures.

    Science.gov (United States)

    Zhang, Tianxi; Li, Yuzhuo; Mueller, Anja

    2011-11-01

    Gas microbubbles present in ultrasound imaging contrast agents are stabilized by lipid aggregates that typically contain a mixture of lipids. In this study, the phase structure of the lipid mixtures that contained two or three lipids was investigated using three different methods: dynamic light scattering, (1)H NMR, and microfluidity measurements with fluorescence probes. Three lipids that are commonly present in imaging agents (DPPC, DPPE-PEG, and DPPA) were used. Two types of systems, two-lipid model systems and simulated imaging systems were investigated. The results show that liposomes were the dominant aggregates in all the samples studied. The polar PEG side chains from the PEGylated lipid lead to the formation of micelles and micellar aggregates in small sizes. In the ternary lipid systems, almost all the lipids were present in bilayers with micelles absent and free lipids at very low concentration. These results suggest that liposomes, not micelles, contribute to the stabilization of microbubbles in an ultrasound imaging contrast agent.

  8. Lipid Status and Predisposing Genes in Patients with Diabetes Mellitus Type 1 from Various Ethnic Groups.

    Science.gov (United States)

    Kolesnikova, L I; Kolesnikov, S I; Darenskaya, M A; Grebenkina, L A; Semenova, N V; Osipova, E V; Gnusina, S V; Bardymova, T A

    2015-12-01

    The peculiarities of HLA class II profile and lipid metabolism were examined in Buryat and Russian ethnic groups of patients with diabetes mellitus type 1. The incidence of type 1 haplotypes in HLA class II gene family was lower in Buryats than that in Russians. In comparison with Russians, the course of diabetes mellitus type 1 in Buryat patients was characterized with a lower content of total lipids, triacylglycerols, total cholesterol, and LDL, which probably explains a more favorable course of the disease in Buryat population.

  9. TBscore II

    DEFF Research Database (Denmark)

    Rudolf, Frauke; Lemvik, Grethe; Abate, Ebba;

    2013-01-01

    Abstract Background: The TBscore, based on simple signs and symptoms, was introduced to predict unsuccessful outcome in tuberculosis patients on treatment. A recent inter-observer variation study showed profound variation in some variables. Further, some variables depend on a physician assessing...... them, making the score less applicable. The aim of the present study was to simplify the TBscore. Methods: Inter-observer variation assessment and exploratory factor analysis were combined to develop a simplified score, the TBscore II. To validate TBscore II we assessed the association between start...

  10. Lipid nanoparticle interactions and assemblies

    Science.gov (United States)

    Preiss, Matthew Ryan

    Novel liposome-nanoparticle assemblies (LNAs) provide a biologically inspired route for designing multifunctional bionanotheranostics. LNAs combine the benefits of lipids and liposomes to encapsulate, transport, and protect hydrophilic and hydrophobic therapeutics with functional nanoparticles. Functional nanoparticles endow LNAs with additional capabilities, including the ability to target diseases, triggered drug release, controlled therapeutic output, and diagnostic capabilities to produce a drug delivery system that can effectively and efficiently deliver therapeutics while reducing side effects. Not only could LNAs make existing drugs better, they could also provide an avenue to allow once promising non-approved drugs (rejected due to harmful side effects, inadequate pharmacokinetics, and poor efficacy) to be safely used through targeted and controlled delivery directly to the diseased site. LNAs have the potential to be stimuli responsive, delivering drugs on command by external (ultrasound, RF heating, etc.) or internal (pH, blood sugar, heart rate, etc.) stimuli. Individually, lipids and nanoparticles have been clinically approved for therapy, such as Doxil (a liposomal doxorubicin for cancer treatment), and diagnosis, such as Feridex (an iron oxide nanoparticle an MRI contrast enhancement agent for liver tumors). In order to engineer these multifunctional LNAs for theranostic applications, the interactions between nanoparticles and lipids must be better understood. This research sought to explore the formation, design, structures, characteristics, and functions of LNAs. To achieve this goal, different types of LNAs were formed, specifically magnetoliposomes, bilayer decorated LNAs (DLNAs), and lipid-coated magnetic nanoparticles (LMNPs). A fluorescent probe was embedded in the lipid bilayer of magnetoliposomes allowing the local temperature and membrane fluidity to be observed. When subjected to an electromagnetic field that heated the encapsulated iron

  11. Solid lipid nanoparticles and nanostructured lipid carriers--innovative generations of solid lipid carriers.

    Science.gov (United States)

    Shidhaye, S S; Vaidya, Reshma; Sutar, Sagar; Patwardhan, Arati; Kadam, V J

    2008-10-01

    The first generation of solid lipid carrier systems in nanometer range, Solid Lipid Nanoparticles (SLN), was introduced as an alternative to liposomes. SLN are aqueous colloidal dispersions, the matrix of which comprises of solid biodegradable lipids. SLN are manufactured by techniques like high pressure homogenization, solvent diffusion method etc. They exhibit major advantages such as modulated release, improved bioavailability, protection of chemically labile molecules like retinol, peptides from degradation, cost effective excipients, improved drug incorporation and wide application spectrum. However there are certain limitations associated with SLN, like limited drug loading capacity and drug expulsion during storage, which can be minimized by the next generation of solid lipids, Nanostructured lipid carriers (NLC). NLC are lipid particles with a controlled nanostructure that improves drug loading and firmly incorporates the drug during storage. Owing to their properties and advantages, SLN and NLC may find extensive application in topical drug delivery, oral and parenteral administration of cosmetic and pharmaceutical actives. Cosmeceuticals is emerging as the biggest application target of these carriers. Carrier systems like SLN and NLC were developed with a perspective to meet industrial needs like scale up, qualification and validation, simple technology, low cost etc. This paper reviews present status of SLN and NLC as carrier systems with special emphasis on their application in Cosmeceuticals; it also gives an overview about various manufacturing techniques of SLN and NLC.

  12. Mass Spectrometry Methodology in Lipid Analysis

    OpenAIRE

    Lin Li; Juanjuan Han; Zhenpeng Wang; Jian'an Liu; Jinchao Wei; Shaoxiang Xiong; Zhenwen Zhao

    2014-01-01

    Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics tech...

  13. Lipid bilayers on nano-templates

    Science.gov (United States)

    Noy, Aleksandr; Artyukhin, Alexander B.; Bakajin, Olgica; Stoeve, Pieter

    2009-08-04

    A lipid bilayer on a nano-template comprising a nanotube or nanowire and a lipid bilayer around the nanotube or nanowire. One embodiment provides a method of fabricating a lipid bilayer on a nano-template comprising the steps of providing a nanotube or nanowire and forming a lipid bilayer around the polymer cushion. One embodiment provides a protein pore in the lipid bilayer. In one embodiment the protein pore is sensitive to specific agents

  14. [Lipids, depression and suicide].

    Science.gov (United States)

    Colin, A; Reggers, J; Castronovo, V; Ansseau, M

    2003-01-01

    Polyunsatured fatty acids are made out of a hydrocarbonated chain of variable length with several double bonds. The position of the first double bond (omega) differentiates polyunsatured omega 3 fatty acids (for example: alpha-linolenic acid or alpha-LNA) and polyunsatured omega 6 fatty acids (for example: linoleic acid or LA). These two classes of fatty acids are said to be essential because they cannot be synthetised by the organism and have to be taken from alimentation. The omega 3 are present in linseed oil, nuts, soya beans, wheat and cold water fish whereas omega 6 are present in maize, sunflower and sesame oil. Fatty acids are part of phospholipids and, consequently, of all biological membranes. The membrane fluidity, of crucial importance for its functioning, depends on its lipidic components. Phospholipids composed of chains of polyunsatured fatty acids increase the membrane fluidity because, by bending some chains, double bonds prevent them from compacting themselves perfectly. Membrane fluidity is also determined by the phospholipids/free cholesterol ratio, as cholesterol increases membrane viscosity. A diet based on a high proportion of essential polyunsatured fatty acids (fluid) would allow a higher incorporation of cholesterol (rigid) in the membranes to balance their fluidity, which would contribute to lower blood cholesterol levels. Brain membranes have a very high content in essential polyunsatured fatty acids for which they depend on alimentation. Any dietary lack of essential polyunsatured fatty acids has consequences on cerebral development, modifying the activity of enzymes of the cerebral membranes and decreasing efficiency in learning tasks. The prevalence of depression seems to increase continuously since the beginning of the century. Though different factors most probably contribute to this evolution, it has been suggested that it could be related to an evolution of alimentary patterns in the Western world, in which polyunsatured omega 3

  15. Molecular and immunogenic features of myelin lipids: incitants or modulators of multiple sclerosis?

    Science.gov (United States)

    Podbielska, M; Hogan, E L

    2009-09-01

    Myelin lipids have long been thought to play intriguing roles in the pathogenesis of multiple sclerosis (MS). This review summarizes current understanding of the molecular basis of MS with emphasis on the: (i.) physico-chemical properties, organization and accessibility of the lipids and their distribution within the myelin multilayer; (ii.) characterization of myelin lipid structures, and structure-function relationships relevant to MS mechanisms, and; (iii.) immunogenic and other features of lipids in MS including molecular mimicry, lipid enzyme genetic knockouts, glycolipid-reactive NKT cells, and monoclonal antibody-induced remyelination. New findings associate anti-lipid antibodies with pathophysiological biomarkers and suggest clinical utility. The structure of CD1d-lipid complexed with the lipophilic invariant T cell receptor (iTCR) may be crucial to understanding MS pathogenesis, and design of lipid antigen-specific therapeutics. Novel immuno-modulatory tools for treatment of autoimmune diseases including MS in which there is both constraint of inflammation and stimulation of remyelination are now emerging.

  16. Peroxide-induced cell death and lipid peroxidation in C6 glioma cells.

    Science.gov (United States)

    Linden, Arne; Gülden, Michael; Martin, Hans-Jörg; Maser, Edmund; Seibert, Hasso

    2008-08-01

    Peroxides are often used as models to induce oxidative damage in cells in vitro. The aim of the present study was to elucidate the role of lipid peroxidation in peroxide-induced cell death. To this end (i) the ability to induce lipid peroxidation in C6 rat astroglioma cells of hydrogen peroxide (H2O2), cumene hydroperoxide (CHP) and t-butyl hydroperoxide (t-BuOOH) (ii) the relation between peroxide-induced lipid peroxidation and cell death in terms of time and concentration dependency and (iii) the capability of the lipid peroxidation chain breaking alpha-tocopherol to prevent peroxide-induced lipid peroxidation and/or cell death were investigated. Lipid peroxidation was characterised by measuring thiobarbituric acid reactive substances (TBARS) and, by HPLC, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) and hexanal. Within 2 h CHP, t-BuOOH and H2O2 induced cell death with EC50 values of 59+/-9 microM, 290+/-30 microM and 12+/-1.1 mM, respectively. CHP and t-BuOOH, but not H2O2 induced lipid peroxidation in C6 cells with EC50 values of 15+/-14 microM and 130+/-33 microM, respectively. The TBARS measured almost exclusively consisted of MDA. 4-HNE was mostly not detectable. The concentration of hexanal slightly increased with increasing concentrations of organic peroxides. Regarding time and concentration dependency lipid peroxidation preceded cell death. Pretreatment with alpha-tocopherol (10 microM, 24 h) prevented both, peroxide-induced lipid peroxidation and cell death. The results strongly indicate a major role of lipid peroxidation in the killing of C6 cells by organic peroxides but also that lipid peroxidation is not involved in H2O2 induced cell death.

  17. Hybrid Lipid as Biological Surfactants

    Science.gov (United States)

    Brewster, Robert; Pincus, Phil; Safran, Sam

    2009-03-01

    Systems capable of forming finite-sized, equilibrium domains are of biological interest in the context of membrane rafts where it has been observed that certain cellular functions are mediated by small (nanometric to tens of nanometers) domains with specific lipid composition that differs from the average composition of the membrane. These small domains are composed mainly of lipids with completely saturated hydrocarbon tails that show good orientational order in the membrane. The surrounding phase consists mostly of lipids with at least one unsaturated bond in the hydrocarbon tails which forces a ``kink'' in the chain and inhibits ordering. In vitro, this phase separation can be replicated; however, the finite domains coarsen into macroscopic domains with time. We have extended a model for the interactions of lipids in the membrane, akin to that developed in the group of Schick (Elliott et al., PRL 2006 and Garbes Putzel and Schick, Biophys. J. 2008), which depends entirely on the local ordering of hydrocarbon tails. We generalize this model to an additional species and identify a biologically relevant component, a lipid with one fully saturated hydrocarbon chain and one chain with at least one unsaturated bond, that may serve as a line-active component, capable of reducing the line tension between domains to zero, thus stabilizing finite sized domains in equilibrium.

  18. Immunological Regulation by Bioactive Lipids.

    Science.gov (United States)

    Taketomi, Yoshitaka; Murakami, Makoto

    2017-01-01

     Mast cells originate from hematopoietic stem cells and undergo terminal maturation in the extravascular tissues, in which they are ultimately resident. Mast maturation, phenotype, and function are dictated by the local microenvironment, which has a significant influence on the ability of mast cells to recognize and respond to stimuli. Activation of mast cells can lead to the release of three distinct classes of mediators, including preformed mediators stored in secretory granules, newly transcribed cytokines and chemokines, and de novo-synthesized bioactive lipid mediators. It is currently recognized that bioactive lipids such as arachidonic acid metabolites (prostaglandins and leukotrienes) released from mast cells modulate innate and adaptive immune responses both directly and indirectly through communication with other microenvironmental immune cells or stroma cells. Moreover, mast cells express a variety of lipid receptors and, if activated by bioactive lipids such as arachidonic acid, ω3 fatty acids, lysophospholipids, and their metabolites, can alter the release and production of other mediators including histamine, cytokines, and chemokines, and thereby alter homeostatic or pathophysiological responses. This review focuses on newly identified functional aspects of bioactive lipids with regard to their immune regulation and functional outcomes in both homeostasis and allergic disease.

  19. Altered fructosamine and lipid fractions in subclinical hypothyroidism.

    Science.gov (United States)

    Udupa, Sridevi V; Manjrekar, Poornima A; Udupa, Vinit A; Vivian, D'Souza

    2013-01-01

    Thyroid function disorders lead to changes in the lipoprotein metabolism. To study the lipid and the glycaemic abnormalities in the subclinical hypothyroidism cases and to compare the same with the euthyroid, overt hypothyroid and the hyperthyroid subjects. Four groups, euthyroid (Group-I), hypothyroid (Group-II), subclinical hypothyroid (Group-III) and hyperthyroid (Group-IV), which consisted of 30 subjects each, of either sex, who were aged 25-55 years, underwent Fasting Plasma Glucose (FPG), fructosamine, lipid profile and total T3, T4 and TSH estimations. The subjects who were on lipid lowering or thyroid disorder drugs and known diabetics were excluded from the study. In Group-III, all the lipid fractions were comparable to those of Group-II and they were significantly deranged, as compared to those of Group-I. The fructosamine levels were significantly higher in Group-II and Group-III (p<0.05), but the subclinical hypothyroid pool had statistically lower levels than the hypothyroid pool (376.63±54.73, 587.80±65.10). In the Group-IV patients, the LDL-C levels were significantly higher as compared to those in the euthyroid pool. The fructosamine levels were significantly lower in comparison with both the euthyroid and the hypothyroid pools (both in Groups-II and III). The FPG levels were higher in all the classes of the thyroid abnormalities (subclinical hypothyroidnot significant) but within the reference range of 70-100mg/dl. Since the lipid derangement in subclinical hypothyroidism is on par with that in overt hypothyrodism, the subclinical hypothyroid cases also need to be treated similarly. The fructosamine values which are largely in excess of the FPG values, indicate a higher propensity to glycation and a decreased turnover of the proteins in the hypothyroid and the subclinical hypothyroid pools. Vice versa is true of the hyperthyroid pool. Fructosamine can be included in the thyroid work up of the patients to assess the metabolic function and the

  20. Direct observation of lipid domains in free standing bilayers: from simple to complex lipid mixtures

    DEFF Research Database (Denmark)

    Bagatolli, Luis A

    2003-01-01

    The direct observation of temperature-dependent lipid phase equilibria, using two-photon excitation fluorescence microscopy on giant unilamellar vesicles (GUVs) composed of different lipid mixtures, provides novel information about the physical characteristics of lipid domain coexistence. Physica...

  1. Lipids, lipid droplets and lipoproteins in their cellular context; an ultrastructural approach

    NARCIS (Netherlands)

    Mesman, R.J.

    2013-01-01

    Lipids are essential for cellular life, functioning either organized as bilayer membranes to compartmentalize cellular processes, as signaling molecules or as metabolic energy storage. Our current knowledge on lipid organization and cellular lipid homeostasis is mainly based on biochemical data.

  2. Antitumor Lipids--Structure, Functions, and Medical Applications.

    Science.gov (United States)

    Kostadinova, Aneliya; Topouzova-Hristova, Tanya; Momchilova, Albena; Tzoneva, Rumiana; Berger, Martin R

    2015-01-01

    Cell proliferation and metastasis are considered hallmarks of tumor progression. Therefore, efforts have been made to develop novel anticancer drugs that inhibit both the proliferation and the motility of tumor cells. Synthetic antitumor lipids (ATLs), which are chemically divided into two main classes, comprise (i) alkylphospholipids (APLs) and (ii) alkylphosphocholines (APCs). They represent a new entity of drugs with distinct antiproliferative properties in tumor cells. These compounds do not interfere with the DNA or mitotic spindle apparatus of the cell, instead, they incorporate into cell membranes, where they accumulate and interfere with lipid metabolism and lipid-dependent signaling pathways. Recently, it has been shown that the most commonly studied APLs inhibit proliferation by inducing apoptosis in malignant cells while leaving normal cells unaffected and are potent sensitizers of conventional chemo- and radiotherapy, as well as of electrical field therapy. APLs resist catabolic degradation to a large extent, therefore accumulate in the cell and interfere with lipid-dependent survival signaling pathways, notably PI3K-Akt and Raf-Erk1/2, and de novo phospholipid biosynthesis. They are internalized in the cell membrane via raft domains and cause downstream reactions as inhibition of cell growth and migration, cell cycle arrest, actin stress fibers collapse, and apoptosis. This review summarizes the in vitro, in vivo, and clinical trials of most common ATLs and their mode of action at molecular and biochemical levels.

  3. Mass Spectrometry Methodology in Lipid Analysis

    Directory of Open Access Journals (Sweden)

    Lin Li

    2014-06-01

    Full Text Available Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics technology greatly push forward the study of lipidomics. Among them, mass spectrometry (MS is the most important technology for lipid analysis. In this review, the methodology based on MS for lipid analysis was introduced. It is believed that along with the rapid development of MS and its further applications to lipid analysis, more functional lipids will be identified as biomarkers and therapeutic targets and for the study of the mechanisms of disease.

  4. Identification of Lipid Binding Modulators Using the Protein-Lipid Overlay Assay.

    Science.gov (United States)

    Tang, Tuo-Xian; Xiong, Wen; Finkielstein, Carla V; Capelluto, Daniel G S

    2017-01-01

    The protein-lipid overlay assay is an inexpensive, easy-to-implement, and high-throughput methodology that employs nitrocellulose membranes to immobilize lipids in order to rapid screen and identify protein-lipid interactions. In this chapter, we show how this methodology can identify potential modulators of protein-lipid interactions by screening water-soluble lipid competitors or even the introduction of pH changes during the binding assay to identify pH-dependent lipid binding events.

  5. Blood lipids and prostate cancer

    DEFF Research Database (Denmark)

    Bull, Caroline J; Bonilla, Carolina; Holly, Jeff M P

    2016-01-01

    Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL...... into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL......, comparing high- (≥7 Gleason score) versus low-grade (cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0...

  6. Fuel from microalgae lipid products

    Energy Technology Data Exchange (ETDEWEB)

    Hill, A.M.; Feinberg, D.A.

    1984-04-01

    The large-scale production of microalgae is a promising method of producing a renewable feedstock for a wide variety of fuel products currently refined from crude petroleum. These microalgae-derived products include lipid extraction products (triglycerides, fatty acids, and hydrocarbons) and catalytic conversion products (paraffins and olefins). Microalgal biomass productivity and lipid composition of current experimental systems are estimated at 66.0 metric tons per hectare year and 30% lipid content. Similar yields in a large-scale facility indicate that production costs are approximately six times higher than the average domestic price for crude, well-head petroleum. Based on achievable targets for productivity and production costs, the potential for microalgae as a fuel feedstock is presented in context with selected process refining routes and is compared with conventional and alternative feedstocks (e.g., oilseeds) with which microalgae must compete. 24 references, 9 figures, 4 tables.

  7. Yeast lipid metabolism at a glance.

    Science.gov (United States)

    Klug, Lisa; Daum, Günther

    2014-05-01

    During the last decades, lipids have gained much attention due to their involvement in health and disease. Lipids are required for the formation of membranes and contribute to many different processes such as cell signaling, energy supply, and cell death. Various organelles such as the endoplasmic reticulum, mitochondria, peroxisomes, and lipid droplets are involved in lipid metabolism. The yeast Saccharomyces cerevisiae has become a reliable model organism to study biochemistry, molecular biology, and cell biology of lipids. The availability of mutants bearing defects in lipid metabolic pathways and the ease of manipulation by culture conditions facilitated these investigations. Here, we summarize the current knowledge about lipid metabolism in yeast. We grouped this large topic into three sections dealing with (1) fatty acids; (2) membrane lipids; and (3) storage lipids. Fatty acids serve as building blocks for the synthesis of membrane lipids (phospholipids, sphingolipids) and storage lipids (triacylglycerols, steryl esters). Phospholipids, sterols, and sphingolipids are essential components of cellular membranes. Recent investigations addressing lipid synthesis, degradation, and storage as well as regulatory aspects are presented. The role of enzymes governing important steps of the different lipid metabolic pathways is described. Finally, the link between lipid metabolic and dynamic processes is discussed.

  8. Charge-reversal Lipids, Peptide-based Lipids, and Nucleoside-based Lipids for Gene Delivery

    Science.gov (United States)

    LaManna, Caroline M.; Lusic, Hrvoje; Camplo, Michel; McIntosh, Thomas J.; Barthélémy, Philippe; Grinstaff, Mark W.

    2013-01-01

    Conspectus Twenty years after gene therapy was introduced in the clinic, advances in the technique continue to garner headlines as successes pique the interest of clinicians, researchers, and the public. Gene therapy’s appeal stems from its potential to revolutionize modern medical therapeutics by offering solutions to a myriad of diseases by tailoring the treatment to a specific individual’s genetic code. Both viral and non-viral vectors have been used in the clinic, but the low transfection efficiencies when utilizing non-viral vectors have lead to an increased focus on engineering new gene delivery vectors. To address the challenges facing non-viral or synthetic vectors, specifically lipid-based carriers, we have focused on three main themes throughout our research: 1) that releasing the nucleic acid from the carrier will increase gene transfection; 2) that utilizing biologically inspired designs, such as DNA binding proteins, to create lipids with peptide-based headgroups will improve delivery; and 3) that mimicking the natural binding patterns observed within DNA, by using lipids having a nucleoside headgroup, will give unique supramolecular assembles with high transfection efficiency. The results presented in this Account demonstrate that cellular uptake and transfection efficacy can be improved by engineering the chemical components of the lipid vectors to enhance nucleic acid binding and release kinetics. Specifically, our research has shown that the incorporation of a charge-reversal moiety to initiate change of the lipid from positive to negative net charge during the transfection process improves transfection. In addition, by varying the composition of the spacer (rigid, flexible, short, long, and aromatic) between the cationic headgroup and the hydrophobic chains, lipids can be tailored to interact with different nucleic acids (DNA, RNA, siRNA) and accordingly affect delivery, uptake outcomes, and transfection efficiency. Introduction of a peptide

  9. Distribution of neutral lipids in the lipid droplet core

    DEFF Research Database (Denmark)

    Chaban, Vitaly V; Khandelia, Himanshu

    2014-01-01

    Cholesteryl esters (CEs) are a form of cholesterol (CHOL) storage in the living cells, as opposed to free CHOL. CEs are major constituents of low density lipoprotein particles. Therefore, CEs are implicated in provoking atherosclerosis. Arranged into cytoplasmic lipid droplets (LDs), CEs are stored...

  10. Cholesterol lipids and cholesterol-containing lipid rafts in bacteria.

    Science.gov (United States)

    Huang, Zhen; London, Erwin

    2016-09-01

    Sterols are important components of eukaryotic membranes, but rare in bacteria. Some bacteria obtain sterols from their host or environment. In some cases, these sterols form membrane domains analogous the lipid rafts proposed to exist in eukaryotic membranes. This review describes the properties and roles of sterols in Borrelia and Helicobacter.

  11. Nanoparticle-lipid bilayer interactions studied with lipid bilayer arrays

    Science.gov (United States)

    Lu, Bin; Smith, Tyler; Schmidt, Jacob J.

    2015-04-01

    The widespread environmental presence and commercial use of nanoparticles have raised significant health concerns as a result of many in vitro and in vivo assays indicating toxicity of a wide range of nanoparticle species. Many of these assays have identified the ability of nanoparticles to damage cell membranes. These interactions can be studied in detail using artificial lipid bilayers, which can provide insight into the nature of the particle-membrane interaction through variation of membrane and solution properties not possible with cell-based assays. However, the scope of these studies can be limited because of the low throughput characteristic of lipid bilayer platforms. We have recently described an easy to use, parallel lipid bilayer platform which we have used to electrically investigate the activity of 60 nm diameter amine and carboxyl modified polystyrene nanoparticles (NH2-NP and COOH-NP) with over 1000 lipid bilayers while varying lipid composition, bilayer charge, ionic strength, pH, voltage, serum, particle concentration, and particle charge. Our results confirm recent studies finding activity of NH2-NP but not COOH-NP. Detailed analysis shows that NH2-NP formed pores 0.3-2.3 nm in radius, dependent on bilayer and solution composition. These interactions appear to be electrostatic, as they are regulated by NH2-NP surface charge, solution ionic strength, and bilayer charge. The ability to rapidly measure a large number of nanoparticle and membrane parameters indicates strong potential of this bilayer array platform for additional nanoparticle bilayer studies.The widespread environmental presence and commercial use of nanoparticles have raised significant health concerns as a result of many in vitro and in vivo assays indicating toxicity of a wide range of nanoparticle species. Many of these assays have identified the ability of nanoparticles to damage cell membranes. These interactions can be studied in detail using artificial lipid bilayers, which

  12. Novel pH-Sensitive Cationic Lipids with Linear Ortho Ester Linkers for Gene Delivery

    Science.gov (United States)

    Chen, Haigang; Zhang, Huizhen; Thor, Der; Rahimian, Roshanak; Guo, Xin

    2012-01-01

    In an effort to develop pH-sensitive lipoplexes for efficient gene delivery, we report three novel cationic lipids containing a linear ortho ester linker that conjugates either the headgroup (Type I) or one hydrocarbon chain (Type II) with the rest of the lipid molecule. The cationic lipids carry either an iodide or a chloride counterion. Compared to our previously reported cyclic ortho ester linker, the linear ortho ester linker facilitated the construction of cationic liposomes and lipoplexes with different helper lipids. The chloride counterion not only facilitated the hydration of the lipid films during liposome construction, but also enhanced the hydrolysis of the ortho ester linker in the lipoplexes. After incubation at endosomal pH 5.5, the Type I lipoplexes aggregated and destabilized the endosome-mimicking model liposomes, but not the Type II lipoplexes. The helper lipids (DOPE or cholesterol) of the lipoplexes enhanced the pH-sensitivity of the Type I lipoplexes. In CV-1 cells (monkey kidney fibroblast), the Type I ortho ester-based lipoplexes, especially those with the chloride counterion, significantly improved the gene transfection efficiency, in some cases by more than 100 fold, compared to their pH-insensitive counterparts consisting of DOTAP. The gene transfection efficiency of the ortho ester-based lipoplexes was well correlated with their rate of aggregation and membrane destabilization in response to the endosomal pH 5.5. PMID:22480493

  13. High lipid productivity of an Ankistrodesmus-Rhizobium artificial consortium.

    Science.gov (United States)

    Do Nascimento, Mauro; Dublan, Maria de los Angeles; Ortiz-Marquez, Juan Cesar Federico; Curatti, Leonardo

    2013-10-01

    Microalgae have great potential as alternative productive platforms for sustainable production of bioenergy, food, feed and other commodities. Process optimization to realize the claimed potential often comprises strains selection and improvement and also developing of more efficient cultivation, harvesting and downstream processing technology. In this work we show that inoculation with the bacterium Rhizobium strain 10II resulted in increments of up to 30% in chlorophyll, biomass and lipids accumulation of the oleaginous microalgae Ankistrodesmus sp. strain SP2-15. Inoculated cultures have reached a high lipid productivity of up to 112 mg L(-1) d(-1) after optimization. The resulting biomass presented significant levels of Ω3 fatty acids including stearidonic acid, suggesting potential as an alternative land-based source of essential fatty acids.

  14. You Sank My Lipid Rafts!

    Science.gov (United States)

    Campbell, Tessa N.

    2009-01-01

    The plasma membrane is the membrane that serves as a boundary between the interior of a cell and its extracellular environment. Lipid rafts are microdomains within a cellular membrane that possess decreased fluidity due to the presence of cholesterol, glycolipids, and phospholipids containing longer fatty acids. These domains are involved in many…

  15. Lipid membranes on nanostructured silicon.

    Energy Technology Data Exchange (ETDEWEB)

    Slade, Andrea Lynn; Lopez, Gabriel P. (University of New Mexico, Albuquerque, NM); Ista, Linnea K. (University of New Mexico, Albuquerque, NM); O' Brien, Michael J. (University of New Mexico, Albuquerque, NM); Sasaki, Darryl Yoshio; Bisong, Paul (University of New Mexico, Albuquerque, NM); Zeineldin, Reema R. (University of New Mexico, Albuquerque, NM); Last, Julie A.; Brueck, Stephen R. J. (University of New Mexico, Albuquerque, NM)

    2004-12-01

    A unique composite nanoscale architecture that combines the self-organization and molecular dynamics of lipid membranes with a corrugated nanotextured silicon wafer was prepared and characterized with fluorescence microscopy and scanning probe microscopy. The goal of this project was to understand how such structures can be assembled for supported membrane research and how the interfacial interactions between the solid substrate and the soft, self-assembled material create unique physical and mechanical behavior through the confinement of phases in the membrane. The nanometer scale structure of the silicon wafer was produced through interference lithography followed by anisotropic wet etching. For the present study, a line pattern with 100 nm line widths, 200 nm depth and a pitch of 360 nm pitch was fabricated. Lipid membranes were successfully adsorbed on the structured silicon surface via membrane fusion techniques. The surface topology of the bilayer-Si structure was imaged using in situ tapping mode atomic force microscopy (AFM). The membrane was observed to drape over the silicon structure producing an undulated topology with amplitude of 40 nm that matched the 360 nm pitch of the silicon structure. Fluorescence recovery after photobleaching (FRAP) experiments found that on the microscale those same structures exhibit anisotropic lipid mobility that was coincident with the silicon substructure. The results showed that while the lipid membrane maintains much of its self-assembled structure in the composite architecture, the silicon substructure indeed influences the dynamics of the molecular motion within the membrane.

  16. Lipids of the Golgi membrane

    NARCIS (Netherlands)

    van Meer, G.

    1998-01-01

    The thin membrane of the endoplasmic reticulum matures into the thick plasma membrane in the Golgi apparatus. Along the way, the concentrations of cholesterol and sphingolipids increase. Here, Gerrit van Meer discusses how this phenomenon may reflect an intricate lipid-protein sorting machinery. Syn

  17. The Membrane and Lipids as Integral Participants in Signal Transduction: Lipid Signal Transduction for the Non-Lipid Biochemist

    Science.gov (United States)

    Eyster, Kathleen M.

    2007-01-01

    Reviews of signal transduction have often focused on the cascades of protein kinases and protein phosphatases and their cytoplasmic substrates that become activated in response to extracellular signals. Lipids, lipid kinases, and lipid phosphatases have not received the same amount of attention as proteins in studies of signal transduction.…

  18. Exogenous ether lipids predominantly target mitochondria.

    Directory of Open Access Journals (Sweden)

    Lars Kuerschner

    Full Text Available Ether lipids are ubiquitous constituents of cellular membranes with no discrete cell biological function assigned yet. Using fluorescent polyene-ether lipids we analyzed their intracellular distribution in living cells by microscopy. Mitochondria and the endoplasmic reticulum accumulated high amounts of ether-phosphatidylcholine and ether-phosphatidylethanolamine. Both lipids were specifically labeled using the corresponding lyso-ether lipids, which we established as supreme precursors for lipid tagging. Polyfosine, a fluorescent analogue of the anti-neoplastic ether lipid edelfosine, accumulated to mitochondria and induced morphological changes and cellular apoptosis. These data indicate that edelfosine could exert its pro-apoptotic power by targeting and damaging mitochondria and thereby inducing cellular apoptosis. In general, this study implies an important role of mitochondria in ether lipid metabolism and intracellular ether lipid trafficking.

  19. Substrate-supported lipid nanotube arrays.

    Energy Technology Data Exchange (ETDEWEB)

    Smirnov, A. I.; Poluektov, O. G.; Chemistry; North Carolina State

    2003-07-16

    This Communication describes the self-assembly of phospholipids into lipid nanotubes inside nanoporous anodic aluminum oxide substrate. Orientations of the lipid molecules in such lipid nanoscale structures were verified by high-resolution spin labeling EPR at 95 GHz. The static order parameter of lipids in such nanotube arrays was determined from low-temperature EPR spectra and was found to be exceptionally high, S{sub static} {approx} 0.9. We propose that substrate-supported lipid nanotube arrays have potential for building robust biochips and biosensors in which rigid nanoporous substrates protect the bilayer surface from contamination. The total bilayer surface in the lipid nanotube arrays is much greater than that in the planar substrate-supported membranes. The lipid nanotube arrays seem to be suitable for developing patterned lipid deposition and could be potentially used for patterning of membrane-associated molecules.

  20. Type II fatty acid synthesis is essential only for malaria parasite late liver stage development

    OpenAIRE

    Vaughan, Ashley M.; O'Neill, Matthew T.; Tarun, Alice S.; Camargo, Nelly; Phuong, Thuan M; Aly, Ahmed S I; Cowman, Alan F.; Kappe, Stefan H. I.

    2008-01-01

    Intracellular malaria parasites require lipids for growth and replication. They possess a prokaryotic type II fatty acid synthesis (FAS II) pathway that localizes to the apicoplast plastid organelle and is assumed to be necessary for pathogenic blood stage replication. However, the importance of FAS II throughout the complex parasite life cycle remains unknown. We show in a rodent malaria model that FAS II enzymes localize to the sporozoite and liver stage apicoplast. Targeted deletion of Fab...

  1. Physical mechanisms of micro- and nanodomain formation in multicomponent lipid membranes

    CERN Document Server

    Schmid, Friederike

    2016-01-01

    This article summarizes a variety of physical mechanisms proposed in the literature, which can generate micro- and nanodomains in multicomponent lipid bilayers and biomembranes. It mainly focusses on lipid-driven mechanisms that do not involve direct protein-protein interactions. Specifically, it considers (i) equilibrium mechanisms based on lipid-lipid phase separation such as critical cluster formation close to critical points, and multiple domain formation in curved geometries, (ii) equilibrium mechanisms that stabilize two-dimensional microemulsions, such as the effect of linactants and the effect of curvature-composition coupling in bilayers and monolayers, and (iii) non-equilibrium mechanisms induced by the interaction of a biomembrane with the cellular environment, such as membrane recycling and the pinning effects of the cytoplasm. Theoretical predictions are discussed together with simulations and experiments. The presentation is guided by the theory of phase transitions and critical phenomena, and t...

  2. Spin trapping studies of essential oils in lipid systems

    Directory of Open Access Journals (Sweden)

    Makarova Katerina

    2015-07-01

    Full Text Available In the present work, we report the results of a spin trapping ESR study of four essential oils widely used for skin care products such as creams and bath salts. The studied essential oils are Rosmarini aetheroleum (rosemary, Menthae piperitae aetheroleum (mint, Lavandulae aetheroleum (lavender, and Thymi aetheroleum (thyme. Fenton reaction in the presence of ethanol was used to generate free radicals. The N-tert-butyl-α-phenylnitrone (PBN was used as a spin trap. In the Fenton reaction, the rosemary oil had the lowest effect on radical adduct formation as compared to the reference Fenton system. Since essential oils are known to be lipid soluble, we also conducted studies of essential oils in Fenton reaction in the presence of lipids. Two model lipids were used, namely 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC. The obtained results suggested that in the presence of DOPC lipids, the •OH and PBN/•CHCH3(OH radicals are formed in both phases, that is, water and lipids, and all the studied essential oils affected the Fenton reaction in a similar way. Whereas, in the DPPC system, the additional type of PBN/X (aN = 16.1 G, aH = 2.9 G radical adduct was generated. DFT calculations of hyperfine splittings were performed at B3LYP/6-311+G(d,p/EPR-II level of theory for the set of c-centered PBN adducts in order to identify PBN/X radical.

  3. Felipe II

    Directory of Open Access Journals (Sweden)

    Carlos Restrepo Canal

    1962-04-01

    Full Text Available Como parte de la monumental Historia de España que bajo la prestante y acertadísima dirección de don Ramón Menéndez Pidal se comenzó a dar a la prensa desde 1954 por la Editorial Espasa Calpe S. A., aparecieron en 1958 dos tomos dedicados al reinado de Felipe II; aquella época en que el imperio español alcanzó su unidad peninsular juntamente con el dilatado poderío que le constituyó en la primera potencia de Europa.

  4. Spontaneous Formation of Lipid Nanotubes and Lipid Nanofibers from Giant Charged Dendrimer Lipids

    Science.gov (United States)

    Zidovska, Alexandra; Ewert, Kai K.; Safinya, Cyrus R.; Quispe, Joel; Carragher, Bridgett; Potter, Clinton S.

    2007-03-01

    Liposomes have attracted much scientific interest due to their applications in model cells studies and in drug encapsulation. We report on the discovery of new vesicle phases formed in mixtures of MVLBG2, DOPC and water. MVLBG2 is a newly synthesized highly charged (16+) lipid (K. Ewert et al., JACS, 2006) with giant dendrimer headgroup thus leading to a high spontaneous curvature of the molecule. In combination with zero-curvature DOPC, MVLBG2 exhibits a rich phase diagram showing novel vesicle morphologies such as bones, lipid nanotubes and nanofibers as revealed by differential contrast microscopy (DIC) and cryo-TEM. At the micron scale DIC reveals a new phase consisting of bone-like vesicles. This novel morphology persists down to the nanometer scale as shown by cryo-TEM. The nanotubes are of diameter 10-50 nm, length > 1μm and consist of a single lipid bilayer. A surprising new morphology arises resulting from a spontaneous topological transition from tubes to lipid nanorods. Funded by DOE DE-FG-02-06ER46314, NIH GM-59288, NSF DMR-0503347.

  5. Myoglobin-induced lipid oxidation : A review

    DEFF Research Database (Denmark)

    Baron, Caroline; Andersen, H.J.

    2002-01-01

    An overview of myoglobin-initiated lipid oxidation in simple model systems, muscle, and muscle-based foods is presented. The potential role of myoglobin spin and redox states in initiating lipid oxidation is reviewed. Proposed mechanisms for myoglobin- initiated lipid oxidation in muscle tissue (p...

  6. How Do Lipids Localize in Lewy Bodies?

    NARCIS (Netherlands)

    Chaudhary, Himanshu; Subramaniam, Vinod; Claessens, Mireille

    2014-01-01

    Lewy bodies are the pathological hallmark of Parkinson's disease (PD). While fibrillar α-synuclein (αS) is the main protein component of Lewy bodies, these structures also contain lipids. To elucidate the presence of lipids in Lewy bodies, we investigated the interaction of lipids with monomeric and

  7. 4-Hydroxy-nonenal—A Bioactive Lipid Peroxidation Product

    Directory of Open Access Journals (Sweden)

    Rudolf J. Schaur

    2015-09-01

    Full Text Available This review on recent research advances of the lipid peroxidation product 4-hydroxy-nonenal (HNE has four major topics: I. the formation of HNE in various organs and tissues, II. the diverse biochemical reactions with Michael adduct formation as the most prominent one, III. the endogenous targets of HNE, primarily peptides and proteins (here the mechanisms of covalent adduct formation are described and the (patho- physiological consequences discussed, and IV. the metabolism of HNE leading to a great number of degradation products, some of which are excreted in urine and may serve as non-invasive biomarkers of oxidative stress.

  8. Rosiglitazone and Fenofibrate Additive Effects on Lipids

    Directory of Open Access Journals (Sweden)

    Ahmad Slim

    2011-01-01

    Full Text Available Background. To evaluate the effect of rosiglitazone, fenofibrate, or their combined use on plasma lipids in normoglycemic healthy adults. Methods and Results. Subjects were randomized in a double-blind fashion to rosiglitazone + placebo, fenofibrate + placebo, rosiglitazone + fenofibrate, or matching double placebo. The between-group difference in the change in fasting TG, high-density lipoprotein cholesterol (HDL-C, LDL-C, and plasma apolipoproteins A-I, A-II, and C-III level were compared after 12 weeks of treatment. A total of 548 subjects were screened and 41 met the inclusion criteria. After 12 weeks of therapy, the median change in the triglyceride levels showed a significant reduction ranging from 47 to 55 mg per deciliter in the fenofibrate only and rosiglitazone/fenofibrate groups compared with placebo (=0.0496. However, the rosiglitazone only group did not show significant change in triglyceride level. The change in the Apo AII showed increase in all the treatment groups compared with placebo (=0.009. There was also significant change in the Apo CIII that showed reduction of its level in the fenofibrate only and rosiglitazone/fenofibrate groups (=0.0003. Conclusion. Rosiglitazone does not appear to modulate hypertriglyceridemia in patients with elevated triglycerides independent of glucose metabolism.

  9. Polydopamine-Supported Lipid Bilayers

    Directory of Open Access Journals (Sweden)

    Souryvanh Nirasay

    2012-12-01

    Full Text Available We report the formation of lipid membranes supported by a soft polymeric cushion of polydopamine. First, 20 nm thick polydopamine films were formed on mica substrates. Atomic force microscopy imaging indicated that these films were also soft with a surface roughness of 2 nm under hydrated conditions. A zwitterionic phospholipid bilayer was then deposited on the polydopamine cushion by fusion of dimyristoylphosphatidylcholine (DMPC and dioleoylphosphatidylcholine (DOPC vesicles. Polydopamine films preserved the lateral mobility of the phospholipids as shown by fluorescence microscopy recovery after photobleaching (FRAP experiments. Diffusion coefficients of ~5.9 and 7.2 µm2 s−1 were respectively determined for DMPC and DOPC at room temperature, values which are characteristic of lipids in a free standing bilayer system.

  10. Polydopamine-Supported Lipid Bilayers

    Science.gov (United States)

    Nirasay, Souryvanh; Badia, Antonella; Leclair, Grégoire; Claverie, Jerome P.; Marcotte, Isabelle

    2012-01-01

    We report the formation of lipid membranes supported by a soft polymeric cushion of polydopamine. First, 20 nm thick polydopamine films were formed on mica substrates. Atomic force microscopy imaging indicated that these films were also soft with a surface roughness of 2 nm under hydrated conditions. A zwitterionic phospholipid bilayer was then deposited on the polydopamine cushion by fusion of dimyristoylphosphatidylcholine (DMPC) and dioleoylphosphatidylcholine (DOPC) vesicles. Polydopamine films preserved the lateral mobility of the phospholipids as shown by fluorescence microscopy recovery after photobleaching (FRAP) experiments. Diffusion coefficients of ~5.9 and 7.2 µm2 s−1 were respectively determined for DMPC and DOPC at room temperature, values which are characteristic of lipids in a free standing bilayer system.

  11. Effects of ovariectomy and resistance training on lipid content in skeletal muscle, liver, and heart; fat depots; and lipid profile

    National Research Council Canada - National Science Library

    Baldissera, Vilmar; de Andrade Perez, Sérgio Eduardo; Prestes, Jonato; Domingos, Mateus Moraes; Shiguemoto, Gilberto Eiji; Pereira, Guilherme Borges; Bernardes, Celene Fernandes; Duarte, Josiane Oliveira; Leite, Richard Diego

    2009-01-01

    The aim of the present study was to investigate the effects of resistance training on skeletal muscle lipid content, liver lipid content, heart lipid content, fat depots, and lipid profile in ovariectomized rats...

  12. Anesthetics interacting with lipid rafts.

    Science.gov (United States)

    Bandeiras, Cátia; Serro, Ana Paula; Luzyanin, Konstantin; Fernandes, Anabela; Saramago, Benilde

    2013-01-23

    The exact mechanism by which anesthetics induce cell membrane-mediated modifications is still an open question. Although the fluidization effect of the anesthetic molecules on the cellular membrane is widely recognized, it is not known if anesthetics show any preference for specific membrane domains, namely the lipid rafts. The importance of these membrane micro-domains derives from the fact that they have been associated with cell signaling pathways, as well as with specific drug interactions. The objective of this work is to contribute for the elucidation of this question through the comparison of the anesthetic interactions with membranes of various lipid compositions. Liposomes prepared with an equimolar mixture of POPC, sphingomyelin and cholesterol, were chosen as models for lipid rafts. The interactions of these liposomes with two local anesthetics, tetracaine and lidocaine, and one general anesthetic, propofol, were studied. The effect of cholesterol was investigated by comparing anesthetic interactions with POPC/SM liposomes and POPC/SM/CHOL liposomes. The following experimental techniques were used: quartz crystal microbalance with dissipation, differential scanning calorimetry and phosphorus nuclear magnetic resonance. Although the liposomes investigated by the different techniques are not in the same conditions, it is possible to assemble the information obtained from all experimental techniques employed to reach a general conclusion. Tetracaine interacts more with raftlike domains, lidocaine induces stronger modifications on POPC/SM liposomes and the results for propofol are not fully conclusive but it seems to be the least prone to lipid interactions. The results were compared with those obtained with DMPC-containing liposomes, reported in a previous work.

  13. Dynamics of multicomponent lipid membranes

    Science.gov (United States)

    Camley, Brian Andrew

    We present theoretical and computational descriptions of the dynamics of multicomponent lipid bilayer membranes. These systems are both model systems for "lipid rafts" in cell membranes and interesting physical examples of quasi-two-dimensional fluids. Our chief tool is a continuum simulation that uses a phase field to track the composition of the membrane, and solves the hydrodynamic equations exactly using the appropriate Green's function (Oseen tensor) for the membrane. We apply this simulation to describe the diffusion of domains in phase-separated membranes, the dynamics of domain flickering, and the process of phase separation in lipid membranes. We then derive an analytical theory to describe domain flickering that is consistent with our simulation results, and use this to analyze experimental measurements of membrane domains. Through this method, we measure the membrane viscosity solely from fluorescence microscopy measurements. We study phase separation in quasi-two-dimensional membranes in depth with both simulations and scaling theory, and classify the different scaling regimes and morphologies, which differ from pure two-dimensional fluids. Our results may explain previous inconsistent measurements of the dynamical scaling exponent for phase separation in membranes. We also extend our theory beyond the simplest model, including the possibility that the membrane will be viscoelastic, as well as considering the inertia of the membrane and the fluid surrounding the membrane.

  14. Stratum corneum barrier lipids in cholesteatoma

    DEFF Research Database (Denmark)

    Svane-Knudsen, V; Halkier-Sørensen, L; Rasmussen, G;

    2000-01-01

    Specimens from primary cholesteatomas were examined under the electron microscope using a lipid-retaining method that is best suited for intracellular lipids and a method that is best for intercellular lipids. In the stratum granulosum of the squamous epithelium, a large number of Odland bodies...... emerged. When the corneocyte reaches the transitional stage to the stratum corneum, the Odland bodies accumulate near the cell membrane and discharge their contents of lipid and enzymes. The lipids are reorganized into multiple long sheets of lamellar structures that embrace the keratinized corneocytes......, as seen in the formation and maintenance of the cutaneous permeability barrier. In this study we draw the attention to the facts that the cholesteatoma epithelium is capable of producing not only cholesterol, but also several lipids, and that the lipid molecules are organized in multilamellar structures...

  15. Stratum Corneum Barrier Lipids in Cholesteatoma

    DEFF Research Database (Denmark)

    Svane-Knudsen, V; Halkier-Sørensen, L; Rasmussen, G

    2000-01-01

    emerged. When the corneocyte reaches the transitional stage to the stratum corneum, the Odland bodies accumulate near the cell membrane and discharge their contents of lipid and enzymes. The lipids are reorganized into multiple long sheets of lamellar structures that embrace the keratinized corneocytes......Specimens from primary cholesteatomas were examined under the electron microscope using a lipid-retaining method that is best suited for intracellular lipids and a method that is best for intercellular lipids. In the stratum granulosum of the squamous epithelium, a large number of Odland bodies......, as seen in the formation and maintenance of the cutaneous permeability barrier. In this study we draw the attention to the facts that the cholesteatoma epithelium is capable of producing not only cholesterol, but also several lipids, and that the lipid molecules are organized in multilamellar structures...

  16. Introduction to fatty acids and lipids.

    Science.gov (United States)

    Burdge, Graham C; Calder, Philip C

    2015-01-01

    The purpose of this article is to describe the structure, function and metabolism of fatty acids and lipids that are of particular importance in the context of parenteral nutrition. Lipids are a heterogeneous group of molecules that share the common property of hydrophobicity. Lipids range in structure from simple short hydrocarbon chains to more complex molecules, including triacylglycerols, phospholipids and sterols and their esters. Lipids within each class may differ structurally. Fatty acids are common components of complex lipids, and these differ according to chain length and the presence, number and position of double bonds in the hydrocarbon chain. Structural variation among complex lipids and among fatty acids gives rise to functional differences that result in different impacts upon metabolism and upon cell and tissue responses. Fatty acids and complex lipids exhibit a variety of structural variations that influence their metabolism and their functional effects.

  17. Lipid metabolism in Drosophila: development and disease

    Institute of Scientific and Technical Information of China (English)

    Zhonghua Liu; Xun Huang

    2013-01-01

    Proteins,nucleic acids,and lipids are three major components of the cell.Despite a few basic metabolic pathways,we know very little about lipids,compared with the explosion of knowledge about proteins and nucleic acids.How many different forms of lipids are there? What are the in vivo functions of individual lipid? How does lipid metabolism contribute to normal development and human health? Many of these questions remain unanswered.For over a century,the fruit fly Drosophila melanogaster has been used as a model organism to study basic biological questions.In recent years,increasing evidences proved that Drosophila models are highly valuable for lipid metabolism and energy homeostasis researches.Some recent progresses of lipid metabolic regulation during Drosophila development and in Drosophila models of human diseases will be discussed in this review.

  18. mTORC1 signalling mediates PI3K-dependent large lipid droplet accumulation in Drosophila ovarian nurse cells

    Directory of Open Access Journals (Sweden)

    Lawrence B. Mensah

    2017-05-01

    Full Text Available Insulin and insulin-like growth factor signalling (IIS, which is primarily mediated by the PI3-kinase (PI3K/PTEN/Akt kinase signalling cassette, is a highly evolutionarily conserved pathway involved in co-ordinating growth, development, ageing and nutrient homeostasis with dietary intake. It controls transcriptional regulators, in addition to promoting signalling by mechanistic target of rapamycin (mTOR complex 1 (mTORC1, which stimulates biosynthesis of proteins and other macromolecules, and drives organismal growth. Previous studies in nutrient-storing germline nurse cells of the Drosophila ovary showed that a cytoplasmic pool of activated phosphorylated Akt (pAkt controlled by Pten, an antagonist of IIS, cell-autonomously regulates accumulation of large lipid droplets in these cells at late stages of oogenesis. Here, we show that the large lipid droplet phenotype induced by Pten mutation is strongly suppressed when mTor function is removed. Furthermore, nurse cells lacking either Tsc1 or Tsc2, which negatively regulate mTORC1 activity, also accumulate large lipid droplets via a mechanism involving Rheb, the downstream G-protein target of TSC2, which positively regulates mTORC1. We conclude that elevated IIS/mTORC1 signalling is both necessary and sufficient to induce large lipid droplet formation in late-stage nurse cells, suggesting roles for this pathway in aspects of lipid droplet biogenesis, in addition to control of lipid metabolism.

  19. Lipid-lipid and lipid-drug interactions in biological membranes

    Science.gov (United States)

    Martynowycz, Michael W.

    Interactions between lipids and drug molecules in biological membranes help govern proper biological function in organisms. The mechanisms responsible for hydrophobic drug permeation remain elusive. Many small molecule drugs are hydrophobic. These drugs inhibit proteins in the cellular interior. The rise of antibiotic resistance in bacteria is thought to be caused by mutations in protein structure, changing drug kinetics to favor growth. However, small molecule drugs have been shown to have different mechanisms depending in the structure of the lipid membrane of the target cell. Biological membranes are investigated using Langmuir monolayers at the air-liquid interface. These offer the highest level of control in the mimetic system and allow them to be investigated using complementary techniques. Langmuir isotherms and insertion assays are used to determine the area occupied by each lipid in the membrane and the change in area caused by the introduction of a drug molecule, respectively. Specular X-ray reflectivity is used to determine the electron density of the monolayer, and grazing incidence X-ray diffraction is used to determine the in-plane order of the monolayer. These methods determine the affinity of the drug and the mechanism of action. Studies are presented on hydrophobic drugs with mammalian membrane mimics using warfarin along with modified analogues, called superwarfarins. Data shows that toxicity of these modified drugs are modulated by the membrane cholesterol content in cells; explaining several previously unexplained effects of the drugs. Membrane mimics of bacteria are investigated along with their interactions with a hydrophobic antibiotic, novobiocin. Data suggests that permeation of the drug is mediated by modifications to the membrane lipids, and completely ceases translocation under certain circumstances. Circumventing deficiencies in small, hydrophobic drugs is approached by using biologically mimetic oligomers. Peptoids, mimetic of host

  20. Isolation and analysis of membrane lipids and lipid rafts in common carp (Cyprinus carpio L.).

    Science.gov (United States)

    Brogden, Graham; Propsting, Marcus; Adamek, Mikolaj; Naim, Hassan Y; Steinhagen, Dieter

    2014-03-01

    Cell membranes act as an interface between the interior of the cell and the exterior environment and facilitate a range of essential functions including cell signalling, cell structure, nutrient uptake and protection. It is composed of a lipid bilayer with integrated proteins, and the inner leaflet of the lipid bilayer comprises of liquid ordered (Lo) and liquid disordered (Ld) domains. Lo microdomains, also named as lipid rafts are enriched in cholesterol, sphingomyelin and certain types of proteins, which facilitate cell signalling and nutrient uptake. Lipid rafts have been extensively researched in mammals and the presence of functional lipid rafts was recently demonstrated in goldfish, but there is currently very little knowledge about their composition and function in fish. Therefore a protocol was established for the analysis of lipid rafts and membranous lipids in common carp (Cyprinus carpio L.) tissues. Twelve lipids were identified and analysed in the Ld domain of the membrane with the most predominant lipids found in all tissues being; triglycerides, cholesterol, phosphoethanolamine and phosphatidylcholine. Four lipids were identified in lipid rafts in all tissues analysed, triglycerides (33-62%) always found in the highest concentration followed by cholesterol (24-32%), phosphatidylcholine and sphingomyelin. Isolation of lipid rafts was confirmed by identifying the presence of the lipid raft associated protein flotillin, present at higher concentrations in the detergent resistant fraction. The data provided here build a lipid library of important carp tissues as a baseline for further studies into virus entry, protein trafficking or environmental stress analysis.

  1. Ethanol Enhances TGF-β Activity by Recruiting TGF-β Receptors From Intracellular Vesicles/Lipid Rafts/Caveolae to Non-Lipid Raft Microdomains.

    Science.gov (United States)

    Huang, Shuan Shian; Chen, Chun-Lin; Huang, Franklin W; Johnson, Frank E; Huang, Jung San

    2016-04-01

    Regular consumption of moderate amounts of ethanol has important health benefits on atherosclerotic cardiovascular disease (ASCVD). Overindulgence can cause many diseases, particularly alcoholic liver disease (ALD). The mechanisms by which ethanol causes both beneficial and harmful effects on human health are poorly understood. Here we demonstrate that ethanol enhances TGF-β-stimulated luciferase activity with a maximum of 0.5-1% (v/v) in Mv1Lu cells stably expressing a luciferase reporter gene containing Smad2-dependent elements. In Mv1Lu cells, 0.5% ethanol increases the level of P-Smad2, a canonical TGF-β signaling sensor, by ∼ 2-3-fold. Ethanol (0.5%) increases cell-surface expression of the type II TGF-β receptor (TβR-II) by ∼ 2-3-fold from its intracellular pool, as determined by I(125) -TGF-β-cross-linking/Western blot analysis. Sucrose density gradient ultracentrifugation and indirect immunofluorescence staining analyses reveal that ethanol (0.5% and 1%) also displaces cell-surface TβR-I and TβR-II from lipid rafts/caveolae and facilitates translocation of these receptors to non-lipid raft microdomains where canonical signaling occurs. These results suggest that ethanol enhances canonical TGF-β signaling by increasing non-lipid raft microdomain localization of the TGF-β receptors. Since TGF-β plays a protective role in ASCVD but can also cause ALD, the TGF-β enhancer activity of ethanol at low and high doses appears to be responsible for both beneficial and harmful effects. Ethanol also disrupts the location of lipid raft/caveolae of other membrane proteins (e.g., neurotransmitter, growth factor/cytokine, and G protein-coupled receptors) which utilize lipid rafts/caveolae as signaling platforms. Displacement of these membrane proteins induced by ethanol may result in a variety of pathologies in nerve, heart and other tissues.

  2. SREBP-1c Gene Silencing can Decrease Lipid Deposits in Bovine Hepatocytes Cultured in Vitro

    Directory of Open Access Journals (Sweden)

    Qinghua Deng

    2014-05-01

    Full Text Available Background: Fatty liver is a major metabolic disorder that occurs during early lactation in high-producing dairy cows. Sterol regulatory element-binding protein-1c (SREBP-1c is an important transcription factor that regulates lipid synthesis by regulating the expression of lipid metabolism genes. Methods: In this study, we reduced the expression of SREBP-1c by adenovirus-mediated SREBP-1c with a low expression vector (AD-GFP-SREBP-1c to study the effects of SREBP-1c on lipid deposits in bovine hepatocytes. The expression levels and enzyme activities of SERBP-1c and its target genes were determined by real-time PCR, western blot, and ELISA. Results: These results showed that Ad-GFP-SREBP-1c could inhibit SREBP-1c expression. The expression of the lipid synthesis enzyme acetyl-CoA carboxylase (ACC was down-regulated. The expression levels of the lipid oxidation enzymes long-chain fatty acyl-COA synthetase (ACSL-1, carnitine palmitoyltransferase І (CPT-І, carnitine palmitoyltransferase II (CPT- II, and β-hydroxyacyl-CoA-DH (HADH were significantly elevated. Furthermore, the expression levels of factors involved in the assembly and transport of very low-density lipoproteins (VLDLs, such as apolipoprotein B100 (ApoB, apolipoprotein E (ApoE, and microsomal triglyceride transfer protein (MTTP were decreased comparison with the negative control and the blank control groups, but the low-density lipoprotein receptor (LDLR was elevated. The concentrations of TG (triglyceride and VLDL were also reduced. Conclusion: These data suggest that low SREBP-1c expression can decrease lipid synthesis, increase lipid oxidation, and decrease the TG and VLDL content in bovine hepatocytes.

  3. Effect of Fe3+ on the growth and lipid content of Isochrysis galbana

    Science.gov (United States)

    Liu, Zhiyuan; Wang, Guangce

    2014-01-01

    Inducing lipid accumulation in microalgae cells without suppressing cell growth is vital to the economical production of biodiesel from microalgae. In two experiments, we demonstrate that the cell concentration and lipid content of marine microalgae Isochrysis galbana depend upon the iron concentration in the growth media. In Experiment I, adding chelated FeCl3 to the medium at the late exponential growth phase prolonged this phase and increased the lipid content in I. galbana cells. The final cell density and lipid content of I. galbana supplemented with chelated FeCl3 was approximately 2 and 1.65 times higher than that of non-supplemented cultures, respectively. In Experiment II, I. galbana cells in the late exponential phase were collected and re-inoculated into new media containing Fe3+ at various concentrations. The final cell concentration and lipid content were maximized at the highest iron concentration (38% biomass by dry weight at 1.2×10-5 mol/L Fe3+). In this study, intracellular neutral lipid storage was evaluated by fluorescent spectrophotometry using fluorochrome Nile red, and the measurement conditions were optimized.

  4. Antithrombotic lipids from Semen Persicae.

    Science.gov (United States)

    Yang, Nian-Yun; Liu, Li; Tao, Wei-Wei; Duan, Jin-Ao; Liu, Xun-Hong; Huang, Su-Ping

    2011-10-01

    Chemical investigation of Semen Persicae has led to the isolation of decane (1), triolein (2), nonacosanoic acid (3), oleic acid ethyl ester (4), palmitic acid (5), oleic acid (6) and 15,16-dihydroxy-9Z,12Z-octadecadienoic acid 2,3-dihydroxypropyl ester (7). Amongst these, compound 7 is a new lipid. Their structures were elucidated by chemical and extensive spectral analysis. Their anticoagulative activities were also evaluated in vitro, which showed that petroleum ether extract and compounds 5-6 could significantly prolong thrombin time while methanol extract could obviously inhibit platelet aggregation.

  5. Superdiffusion in supported lipid bilayers

    CERN Document Server

    Campagnola, Grace; Schroder, Bryce W; Peersen, Olve B; Krapf, Diego

    2015-01-01

    We study the diffusion of membrane-targeting C2 domains using single-molecule tracking in supported lipid bilayers. The ensemble-averaged mean square displacement (MSD) exhibits superdiffusive behavior. However, the time-averaged MSD of individual trajectories is found to be linear with respect to lag time, as in Brownian diffusion. These observations are explained in terms of bulk excursions that introduce jumps with a heavy-tail distribution. Our experimental results are shown to agree with analytical models of bulk-mediated diffusion and with numerical simulations.

  6. Effect of brown seaweed lipids on fatty acid composition and lipid hydroperoxide levels of mouse liver.

    Science.gov (United States)

    Airanthi, M K Widjaja-Adhi; Sasaki, Naoya; Iwasaki, Sayaka; Baba, Nobuko; Abe, Masayuki; Hosokawa, Masashi; Miyashita, Kazuo

    2011-04-27

    Brown seaweed lipids from Undaria pinnatifida (Wakame), Sargassum horneri (Akamoku), and Cystoseira hakodatensis (Uganomoku) contained several bioactive compounds, namely, fucoxanthin, polyphenols, and omega-3 polyunsaturated fatty acids (PUFA). Fucoxanthin and polyphenol contents of Akamoku and Uganomoku lipids were higher than those of Wakame lipids, while Wakame lipids showed higher total omega-3 PUFA content than Akamoku and Uganomoku lipids. The levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in liver lipids of KK-A(y) mouse significantly increased by Akamoku and Uganomoku lipid feeding as compared with the control, but not by Wakame lipid feeding. Fucoxanthin has been reported to accelerate the bioconversion of omega-3 PUFA and omega-6 PUFA to DHA and AA, respectively. The higher hepatic DHA and AA level of mice fed Akamoku and Uganomoku lipids would be attributed to the higher content of fucoxanthin of Akamoku and Uganomoku lipids. The lipid hydroperoxide levels of the liver of mice fed brown seaweed lipids were significantly lower than those of control mice, even though total PUFA content was higher in the liver of mice fed brown seaweed lipids. This would be, at least in part, due to the antioxidant activity of fucoxanthin metabolites in the liver.

  7. Lipid Disturbances in Psoriasis: An Update

    Directory of Open Access Journals (Sweden)

    Aldona Pietrzak

    2010-01-01

    Full Text Available Psoriasis is a common disease with the population prevalence ranging from 2% to 3%. Its prevalence in the population is affected by genetic, environmental, viral, infectious, immunological, biochemical, endocrinological, and psychological factors, as well as alcohol and drug abuse. In the recent years, psoriasis has been recognised as a systemic disease associated with numerous multiorgan abnormalities and complications. Dyslipidemia is one of comorbidities in psoriatic patients. Lipid metabolism studies in psoriasis have been started at the beginning of the 20th century and are concentrated on skin surface lipids, stratum corneum lipids and epidermal phospholipids, serum lipids, dermal low-density lipoproteins in the psoriatic skin, lipid metabolism, oxidative stress and correlations between inflammatory parameters, lipid parameters and clinical symptoms of the disease. On the basis of the literature data, psoriasis can be described as an immunometabolic disease.

  8. Modulation of the lipidomic profile due to a lipid challenge and fitness level: a postprandial study.

    Science.gov (United States)

    Morris, Ciara; O'Grada, Colm M; Ryan, Miriam F; Gibney, Michael J; Roche, Helen M; Gibney, Eileen R; Brennan, Lorraine

    2015-07-01

    The lipid composition of plasma is known to vary due to both phenotypic factors such as age, gender and BMI as well as with various diseases including cancer and neurological disorders. However, there is little investigation into the variation in the lipidome due to exercise and/ or metabolic challenges. The objectives of this present study were (i) To identify the glycerophospholipid, sphingolipids and ceramide changes in response to an oral lipid tolerance test (OLTT) in healthy adults and (ii) To identify the effect of aerobic fitness level on lipidomic profiles. 214 healthy adults aged 18-60 years were recruited as part of a metabolic challenge study. A sub-group of 40 volunteers were selected for lipidomic analysis based on their aerobic fitness level. Ceramides, glycerophospholipids and sphingomyelins were quantified in baseline fasting plasma samples as well as at 60, 120, 180, 240 and 300 min following a lipid challenge using high-throughput flow injection ESI-MS/MS. Mixed model repeated measures analysis identified lipids which were significantly changing over the time course of the lipid challenge. Included in these lipids were lysophosphoethanolamines (LPE), phosphoethanolamines (PE), phosphoglycerides (PG) and ceramides (Cer). Five lipids (LPE a C18:2, LPE a C18:1, PE aa C36:2, PE aa C36:3 and N-C16:1-Cer) had a fold change > 1.5 at 120 min following the challenge and these lipids remained elevated. Furthermore, three of these lipids (LPE a C18:2, PE aa C36:2 and PE aa C36:3) were predictive of fasting and peak plasma TAG concentrations following the OLTT. Further analysis revealed that fitness level has a significant impact on the response to the OLTT: in particular significant differences between fitness groups were observed for phosphatidylcholines (PC), sphingomyelins (SM) and ceramides. This study identified specific lipids which were modulated by an acute lipid challenge. Furthermore, it identified a series of lipids which were modulated by

  9. Interaction of carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) with lipid membrane systems: a biophysical approach with relevance to mitochondrial uncoupling.

    Science.gov (United States)

    Monteiro, João P; Martins, André F; Lúcio, Marlene; Reis, Salette; Geraldes, Carlos F G C; Oliveira, Paulo J; Jurado, Amália S

    2011-06-01

    FCCP (carbonylcyanide p-trifluoromethoxyphenylhydrazone), a classical uncoupler of mitochondrial oxidative phosphorylation, is used in this study as a model to clarify how interactions of uncouplers with membrane lipid bilayers may influence membrane biophysics and their protonophoric activity itself. In order to disclose putative effects that may be important when considering using uncouplers for pharmacological purposes, an extensive characterization of FCCP membrane lipid interactions using accurate biophysical approaches and simple model lipid systems was carried out. Differential scanning calorimetry studies showed that FCCP molecules disturb lipid bilayers and favor lateral phase separation in mixed lipid systems. (31)P NMR assays indicated that FCCP alters the curvature elastic properties of membrane models containing non-bilayer lipids, favoring lamellar/H(II) transition, probably by alleviation of hydrocarbon-packing constraints in the inverted hexagonal phase. Taking advantage of FCCP quenching effects on the fluorescent probes DPH (1,6-diphenyl-1,3,5-hexatriene) and DPH-PA (3-(p-(6-phenyl)-1,3,5-hexatrienyl)phenylpropionic acid), it is demonstrated that FCCP distributes across the bilayer thickness in both a single and a ternary lipid system mimicking the inner mitochondrial membrane. This behavior is consistent with the ability of the compound to migrate through the thickness of the inner mitochondrial membrane, an event required for its protonophoric activity. Finally, the study of the membrane fluidity in different lipid systems, as reported by the rotational correlation time (θ) of DPH or DPH-PA, showed that the extension at which FCCP disturbs membrane properties associated with the dynamics and the order of lipid molecules depends on the lipid composition of the model lipid system assayed.

  10. Circadian regulators of intestinal lipid absorption

    OpenAIRE

    Hussain, M. Mahmood; Pan, Xiaoyue

    2015-01-01

    Among all the metabolites present in the plasma, lipids, mainly triacylglycerol and diacylglycerol, show extensive circadian rhythms. These lipids are transported in the plasma as part of lipoproteins. Lipoproteins are synthesized primarily in the liver and intestine and their production exhibits circadian rhythmicity. Studies have shown that various proteins involved in lipid absorption and lipoprotein biosynthesis show circadian expression. Further, intestinal epithelial cells express circa...

  11. APP Function and Lipids: A Bidirectional Link.

    Science.gov (United States)

    Grimm, Marcus O W; Mett, Janine; Grimm, Heike S; Hartmann, Tobias

    2017-01-01

    Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer's disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals. Interestingly, the observed lipid changes in the brain seem not only to be a consequence of the disease but also modulate Aβ generation. In line with these observations, protective lipids being able to decrease Aβ generation and also potential negative lipids in respect to AD were identified. Mechanistically, Aβ peptides are generated by sequential proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. The α-secretase appears to compete with β-secretase for the initial cleavage of APP, preventing Aβ production. All APP-cleaving secretases as well as APP are transmembrane proteins, further illustrating the impact of lipids on Aβ generation. Beside the pathological impact of Aβ, accumulating evidence suggests that Aβ and the APP intracellular domain (AICD) play an important role in regulating lipid homeostasis, either by direct effects or by affecting gene expression or protein stability of enzymes involved in the de novo synthesis of different lipid classes. This review summarizes the current literature addressing the complex bidirectional link between lipids and AD and APP processing including lipid alterations found in AD post mortem brains, lipids that alter APP processing and the physiological functions of Aβ and AICD in the regulation of several lipid metabolism pathways.

  12. Stiffnites. Part II

    Directory of Open Access Journals (Sweden)

    Maria Teresa Pareschi

    2011-06-01

    Full Text Available

    The dynamics of a stiffnite are here inferred. A stiffnite is a sheet-shaped, gravity-driven submarine sediment flow, with a fabric made up of marine ooze. To infer stiffnite dynamics, order of magnitude estimations are used. Field deposits and experiments on materials taken from the literature are also used. Stiffnites can be tens or hundreds of kilometers wide, and a few centimeters/ meters thick. They move on the sea slopes over hundreds of kilometers, reaching submarine velocities as high as 100 m/s. Hard grain friction favors grain fragmentation and formation of triboelectrically electrified particles and triboplasma (i.e., ions + electrons. Marine lipids favor isolation of electrical charges. At first, two basic assumptions are introduced, and checked a posteriori: (a in a flowing stiffnite, magnetic dipole moments develop, with the magnetization proportional to the shear rate. I have named those dipoles as Ambigua. (b Ambigua are ‘vertically frozen’ along stiffnite streamlines. From (a and (b, it follows that: (i Ambigua create a magnetic field (at peak, >1 T. (ii Lorentz forces sort stiffnite particles into two superimposed sheets. The lower sheet, L+, has a sandy granulometry and a net positive electrical charge density. The upper sheet, L–, has a silty muddy granulometry and a net negative electrical charge density; the grains of sheet L– become finer upwards. (iii Faraday forces push ferromagnetic grains towards the base of a stiffnite, so that a peak of magnetic susceptibility characterizes a stiffnite deposit. (iv Stiffnites harden considerably during their motion, due to magnetic confinement. Stiffnite deposits and inferred stiffnite characteristics are compatible with a stable flow behavior against bending, pinch, or other macro instabilities. In the present report, a consistent hypothesis about the nature of Ambigua is provided.

  13. Elizabeth II uus kunstigalerii

    Index Scriptorium Estoniae

    1999-01-01

    Tähistamaks oma troonile asumise 50. aastapäeva, avab Elizabeth II 6. II 2002 Buckinghami palees uue kunstigalerii, mis ehitatakse palee tiibhoonena. Arhitekt John Simpson. Elizabeth II kunstikogust

  14. Elizabeth II uus kunstigalerii

    Index Scriptorium Estoniae

    1999-01-01

    Tähistamaks oma troonile asumise 50. aastapäeva, avab Elizabeth II 6. II 2002 Buckinghami palees uue kunstigalerii, mis ehitatakse palee tiibhoonena. Arhitekt John Simpson. Elizabeth II kunstikogust

  15. Dietary Consumption of Virgin Coconut Oil Ameliorates Lipid Profiles in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    A. M. Akinnuga

    2014-01-01

    Full Text Available Virgin coconut oil (VCO is a saturated fat with promising antidiabetic properties but its ameliorative effect on lipid profiles in diabetics is rarely reported. Therefore, in this study, a total of fifteen (15 male rats weighing 200–250 g were divided into 3 experimental groups (n=5. Group I (control and Group II (diabetic control group were fed a normal rat chow while Group III (diabetic test group was fed a 10% VCO diet for 3 weeks. Group II and Group III were made diabetic by intraperitoneal injection of 150 mg/kg of alloxan. After 72 hours of injection, blood glucose was tested to confirm diabetes mellitus. After 3 weeks, the animals were sacrificed to collect blood samples for lipid profile analysis. The results showed a significant increase in concentrations of triglyceride, total cholesterol, low density lipoprotein, and very low density lipoprotein and decrease in concentration of high density lipoprotein in Group II when compared to Group I. Also, the concentrations of triglyceride, total cholesterol, low density lipoprotein, and very low density lipoprotein except high density lipoprotein significantly reduced in Group III when compared to Group II (P<0.01, 0.001. VCO consumption can be claimed to ameliorate lipid levels in diabetes mellitus.

  16. Lipid bilayer composition influences small multidrug transporters

    Directory of Open Access Journals (Sweden)

    Curnow Paul

    2008-11-01

    Full Text Available Abstract Background Membrane proteins are influenced by their surrounding lipids. We investigate the effect of bilayer composition on the membrane transport activity of two members of the small multidrug resistance family; the Escherichia coli transporter, EmrE and the Mycobacterium tuberculosis, TBsmr. In particular we address the influence of phosphatidylethanolamine and anionic lipids on the activity of these multidrug transporters. Phosphatidylethanolamine lipids are native to the membranes of both transporters and also alter the lateral pressure profile of a lipid bilayer. Lipid bilayer lateral pressures affect membrane protein insertion, folding and activity and have been shown to influence reconstitution, topology and activity of membrane transport proteins. Results Both EmrE and TBsmr are found to exhibit a similar dependence on lipid composition, with phosphatidylethanolamine increasing methyl viologen transport. Anionic lipids also increase transport for both EmrE and TBsmr, with the proteins showing a preference for their most prevalent native anionic lipid headgroup; phosphatidylglycerol for EmrE and phosphatidylinositol for TBsmr. Conclusion These findings show that the physical state of the membrane modifies drug transport and that substrate translocation is dependent on in vitro lipid composition. Multidrug transport activity seems to respond to alterations in the lateral forces exerted upon the transport proteins by the bilayer.

  17. Lipid Nanoparticles for Ocular Gene Delivery

    Directory of Open Access Journals (Sweden)

    Yuhong Wang

    2015-06-01

    Full Text Available Lipids contain hydrocarbons and are the building blocks of cells. Lipids can naturally form themselves into nano-films and nano-structures, micelles, reverse micelles, and liposomes. Micelles or reverse micelles are monolayer structures, whereas liposomes are bilayer structures. Liposomes have been recognized as carriers for drug delivery. Solid lipid nanoparticles and lipoplex (liposome-polycation-DNA complex, also called lipid nanoparticles, are currently used to deliver drugs and genes to ocular tissues. A solid lipid nanoparticle (SLN is typically spherical, and possesses a solid lipid core matrix that can solubilize lipophilic molecules. The lipid nanoparticle, called the liposome protamine/DNA lipoplex (LPD, is electrostatically assembled from cationic liposomes and an anionic protamine-DNA complex. The LPD nanoparticles contain a highly condensed DNA core surrounded by lipid bilayers. SLNs are extensively used to deliver drugs to the cornea. LPD nanoparticles are used to target the retina. Age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy are the most common retinal diseases in humans. There have also been promising results achieved recently with LPD nanoparticles to deliver functional genes and micro RNA to treat retinal diseases. Here, we review recent advances in ocular drug and gene delivery employing lipid nanoparticles.

  18. DMSO Induces Dehydration near Lipid Membrane Surfaces

    Science.gov (United States)

    Cheng, Chi-Yuan; Song, Jinsuk; Pas, Jolien; Meijer, Lenny H.H.; Han, Songi

    2015-01-01

    Dimethyl sulfoxide (DMSO) has been broadly used in biology as a cosolvent, a cryoprotectant, and an enhancer of membrane permeability, leading to the general assumption that DMSO-induced structural changes in cell membranes and their hydration water play important functional roles. Although the effects of DMSO on the membrane structure and the headgroup dehydration have been extensively studied, the mechanism by which DMSO invokes its effect on lipid membranes and the direct role of water in this process are unresolved. By directly probing the translational water diffusivity near unconfined lipid vesicle surfaces, the lipid headgroup mobility, and the repeat distances in multilamellar vesicles, we found that DMSO exclusively weakens the surface water network near the lipid membrane at a bulk DMSO mole fraction (XDMSO) of DMSO was found to effectively destabilize the hydration water structure at the lipid membrane surface at XDMSO 0.1, DMSO enters the lipid interface and restricts the lipid headgroup motion. We postulate that DMSO acts as an efficient cryoprotectant even at low concentrations by exclusively disrupting the water network near the lipid membrane surface, weakening the cohesion between water and adhesion of water to the lipid headgroups, and so mitigating the stress induced by the volume change of water during freeze-thaw. PMID:26200868

  19. Lipid peroxides level in the Indonesian elderly

    Directory of Open Access Journals (Sweden)

    Purwantyastuti Purwantyastuti

    2005-06-01

    Full Text Available A cross-sectional study was done to see the possible association of plasma lipid peroxides in the elderly with age and other factors. Plasma lipid peroxides is a product of free radical reactions which according to the latest theory of aging is the cause of aging process. Lipid peroxides were also found high in coronary heart disease. Four hundred forty relatively healthy elderly, age 55-85 years, were randomly chosen from free living elderly under guidance of health care centers (PUSKESMAS in Jakarta. Anamnesis and physical examination were done in the morning in the health centers. Blood samples were taken in fasting conditions, plasma lipids and lipid peroxides were measured according to standard methods. There was an age difference of lipid peroxides level in the elderly, which increased with age up to 70 years old. Elderly 70 years old and over had low plasma lipid peroxides. The level was not related to high plasma lipids. Higher level was found when more chronic degenerative diseases were found. (Med J Indones 2005; 14: 71-7Keywords: lipid peroxides, aging

  20. Electrodiffusion of lipids on membrane surfaces

    Science.gov (United States)

    Zhou, Y. C.

    2012-05-01

    Lateral translocation of lipids and proteins is a universal process on membrane surfaces. Local aggregation or organization of lipids and proteins can be induced when the random lateral motion is mediated by the electrostatic interactions and membrane curvature. Although the lateral diffusion rates of lipids on membranes of various compositions are measured and the electrostatic free energies of predetermined protein-membrane-lipid systems can be computed, the process of the aggregation and the evolution to the electrostatically favorable states remain largely undetermined. Here we propose an electrodiffusion model, based on the variational principle of the free energy functional, for the self-consistent lateral drift-diffusion of multiple species of charged lipids on membrane surfaces. Finite sizes of lipids are modeled to enforce the geometrical constraint of the lipid concentration on membrane surfaces. A surface finite element method is developed to appropriate the Laplace-Beltrami operators in the partial differential equations of the model. Our model properly describes the saturation of lipids on membrane surfaces, and correctly predicts that the MARCKS peptide can consistently sequester three multivalent phosphatidylinositol 4,5-bisphosphate lipids through its basic amino acid residues, regardless of a wide range of the percentage of monovalent phosphatidylserine in the membrane.

  1. Lipid transport in cholecystokinin knockout mice.

    Science.gov (United States)

    King, Alexandra; Yang, Qing; Huesman, Sarah; Rider, Therese; Lo, Chunmin C

    2015-11-01

    Cholecystokinin (CCK) is released in response to lipid feeding and regulates pancreatic digestive enzymes vital to the absorption of nutrients. Our previous reports demonstrated that cholecystokinin knockout (CCK-KO) mice fed for 10 weeks of HFD had reduced body fat mass, but comparable glucose uptake by white adipose tissues and skeletal muscles. We hypothesized that CCK is involved in energy homeostasis and lipid transport from the small intestine to tissues in response to acute treatment with dietary lipids. CCK-KO mice with comparable fat absorption had increased energy expenditure and were resistant to HFD-induced obesity. Using intraduodenal infusion of butter fat and intravenous infusion using Liposyn III, we determined the mechanism of lipid transport from the small intestine to deposition in lymph and adipocytes in CCK-KO mice. CCK-KO mice had delayed secretion of Apo B48-chylomicrons, lipid transport to the lymphatic system, and triglyceride (TG)-derived fatty acid uptake by epididymal fat in response to acute treatment of intraduodenal lipids. In contrast, CCK-KO mice had comparable TG clearance and lipid uptake by white adipocytes in response to TGs in chylomicron-like emulsion. Thus, we concluded that CCK is important for lipid transport and energy expenditure to control body weight in response to dietary lipid feeding.

  2. Biologic Activity of Porphyromonas endodontalis complex lipids

    Science.gov (United States)

    Mirucki, Christopher S.; Abedi, Mehran; Jiang, Jin; Zhu, Qiang; Wang, Yu-Hsiung; Safavi, Kamran E.; Clark, Robert B.; Nichols, Frank C.

    2014-01-01

    Introduction Periapical infections secondary to pulpal necrosis are associated with bacterial contamination of the pulp. Porphyromonas endodontalis, a Gram-negative organism, is considered to be a pulpal pathogen. P. gingivalis is phylogenetically related to P. endodontalis and synthesizes several classes of novel complex lipids that possess biological activity, including the capacity to promote osteoclastogenesis and osteoclast activation. The purpose of this study was to extract and characterize constituent lipids of P. endodontalis, and evaluate their capacity to promote pro-inflammatory secretory responses in the macrophage cell line, RAW 264.7, as well as their capacity to promote osteoclastogenesis and inhibit osteoblast activity. Methods Constituent lipids of both organisms were fractionated by HPLC and were structurally characterized using electrospray-mass spectrometry (ESI-MS) or ESI-MS/MS. The virulence potential of P. endodontalis lipids was then compared with known biologically active lipids isolated from P. gingivalis. Results P. endodontalis total lipids were shown to promote TNF-α secretion from RAW 264.7 cells and the serine lipid fraction appeared to account for the majority of this effect. P. endodontalis lipid preparations also increased osteoclast formation from RAW 264.7 cells but osteoblast differentiation in culture was inhibited and appeared to be dependent on TLR2 expression. Conclusions These effects underscore the importance of P. endodontalis lipids in promoting inflammatory and bone cell activation processes that could lead to periapical pathology. PMID:25146013

  3. Lipid Metabolism, Apoptosis and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Chunfa Huang

    2015-01-01

    Full Text Available Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy.

  4. Impact of lipid content and composition on lipid oxidation and protein carbonylation in experimental fermented sausages.

    Science.gov (United States)

    Fuentes, Verónica; Estévez, Mario; Ventanas, Jesús; Ventanas, Sonia

    2014-03-15

    This study aims to investigate the effect of lipid content (∼4%, ∼10% and ∼15%) and composition (different lipid sources; animal fat and sunflower oil) on the oxidative stability of proteins and lipids in experimental fermented sausages. Increasing the lipid content of sausages enhanced the susceptibility of lipids to oxidation whereas the effect on the formation of specific carbonyls from protein oxidation was not so evident. Sausages manufactured with different lipid sources affected the susceptibility of lipids and proteins to oxidation as a likely result of the modifications in the fatty acid profile, as well as to the presence of antioxidant compounds. While the fatty acid profile had a major effect on the occurrence and extent of lipid oxidation, the presence of compounds with potential antioxidant activity may be more influential on the extent of protein carbonylation.

  5. Clinical controversies in lipid management.

    Science.gov (United States)

    Tziomalos, K

    2015-06-01

    Even though it is firmly established that statins are the cornerstone of management of dyslipidemias, several controversies still exist in this area. In the present review, the most pertinent controversies in lipid management are discussed and the current evidence is summarized. Treatment with statins increases the risk for type 2 diabetes mellitus (T2DM) but this increase appears to be small and outweighed by the benefits of statins on cardiovascular disease prevention. Accordingly, statin treatment-associated T2DM should not affect management decisions. In patients who cannot achieve low-density lipoprotein cholesterol (LDL-C) targets despite treatment with the maximum tolerated dose of a potent statin, adding ezetimibe appears to be the treatment of choice. Finally, patients who achieved LDL-C targets with a statin but have elevated triglyceride levels appear to have increased cardiovascular risk and adding fenofibrate appears to reduce this risk. Even though additional large randomized controlled trials are unlikely to be performed with the existing lipid-lowering agents, mechanistic, genetic and epidemiological studies, as well as careful analyses of the existing trials will provide further insights in these controversial issues and will allow the optimization of the management of dyslipidemia aiming at further reductions in cardiovascular morbidity.

  6. Electroporation of heterogeneous lipid membranes.

    Science.gov (United States)

    Reigada, Ramon

    2014-03-01

    Electroporation is the basis for the transfection of genetic material and for drug delivery to cells, including electrochemotherapy for cancer. By means of molecular dynamics many aspects of membrane electroporation have been unveiled at the molecular detail in simple, homogeneous, lipid bilayers. However, the correspondence of these findings \\with the process happening in cell membranes requires, at least, the consideration of laterally structured membranes. Here, I present a systematic molecular dynamics study of bilayers composed of different liquid-ordered and liquid-disordered lipid phases subjected to a transversal electric field. The simulations reveal two significant results. First, the electric field mainly affects the properties of the disordered phases, so that electroporation takes place in these membrane regions. Second, the smaller the disordered domains are, the faster they become electroporated. These findings may have a relevant significance in the experimental application of cell electroporation in vivo since it implies that electro-induced and pore-mediated transport processes occur in particularly small disordered domains of the plasma membrane, thus locally affecting only specific regions of the cell.

  7. Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous conditions

    Directory of Open Access Journals (Sweden)

    Patel Prabhudas

    2004-01-01

    Full Text Available BACKGROUND : The changes in lipid profile have long been associated with cancer because lipids play a key role in maintenance of cell integrity. AIMS : The present study evaluated alterations in plasma lipid profile in untreated head and neck cancer patients as well as patients with oral precancerous conditions (OPC and its association with habit of tobacco consumption. MATERIAL AND METHODS : This hospital-based case control study included 184 head and neck cancer patients, 153 patients with OPC and 52 controls. Plasma lipids including: (i Total cholesterol, (ii LDL cholesterol (LDLC, (iii HDL cholesterol (HDLC (iv VLDL cholesterol (VLDLC and (v triglycerides were analysed by spectrophotometric kits. STATISTICAL ANALYSIS USED : Student′s t-test was performed to compare mean values of the parameters. RESULTS : A significant decrease in plasma total cholesterol and HDLC was observed in cancer patients (P=0.008 and P=0.000 respectively as well as in patients with OPC (P=0.014 and P=0.000, respectively as compared to the controls. The plasma VLDL and triglycerides levels were significantly lower in cancer patients as compared to the patients with OPC (P=0.04 and controls (P=0.059. The tobacco habituates showed lower plasma lipid levels than the non-habituates. Our data strengthen the evidence of an inverse relationship between plasma lipid levels and head and neck malignancies as well as OPC. CONCLUSION :The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization by neoplastic cells for new membrane biogenesis. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in head neck cancer patients.

  8. Natural lipids in nanostructured lipid carriers and its cytotoxicity

    Science.gov (United States)

    Lima, Paula A.; Rampazo, Caroline A. D.; Costa, Amanda F.; Rodrigues, Tiago; Watashi, Carolina M.; Durán, Nelson

    2017-06-01

    Nanostructured lipid carriers (NLCs) are active carrier systems which modulate the sustained release of actives and protect unstable compounds against degradation. NLCs can also protect skin from sun light, due to its particulates nature, which gives them intrinsic scattering properties. In this work, we present the preparation of NLCs using natural lipids and its cytotoxicity profile. It was used a vegetal butter with melting point (m.p.) ~32-40°C, an animal wax (m.p. 35-40°C) and a vegetal oil (boiling point ~120-150°C). NLCs were prepared by hot high pressure homogenization method and particles were characterized by average size (Zave), polydispersity index (PDI) and zeta potential (PZ) (Fig.1). The thermal behavior of the NLCs was studied using Differential Scanning Calorimetry (DSC). All the formulations were followed up for 60 days in order to evaluate their stability. NLCs exhibited a Zave around 150-200 nm, PDI less than 0.2 and PZ varying from -25 to -40 mV. The m.p. for the lyophilized NLCs was about 40-56°C. Cytotoxicity of the formulations were evaluated for human keratinocytes (HaCaT) and melanocytes (Melan-A) in the exponential growth phase. Cell viability was used as indicator of cytotoxicity and determined after 4 days of culture by MTT assay. It was found that the NLC formulations were not toxic against HaCaT and Melan-A cells. Results showed that the NLCs produced are potential carriers for nanocosmetics and sunscreen products.

  9. Inclusion of the helper lipid dioleoyl-phosphatidylethanolamine in solid lipid nanoparticles inhibits their transfection efficiency

    NARCIS (Netherlands)

    de Jesus, Marcelo B.; Radaic, Allan; Hinrichs, Wouter L J; Ferreira, Carmen V; de Paula, Eneida; Hoekstra, Dirk; Zuhorn, Inge S

    2014-01-01

    Solid lipid nanoparticles (SLNs) are a promising system for the delivery of lipophilic and hydrophilic drugs. They consist of a solid lipid core that is stabilized by a layer of surfactants. By the incorporation of cationic lipids in the formulation, positively charged SLNs can be generated, that ar

  10. Lipids, lipid droplets and lipoproteins in their cellular context; an ultrastructural approach

    NARCIS (Netherlands)

    Mesman, R.J.

    2013-01-01

    Lipids are essential for cellular life, functioning either organized as bilayer membranes to compartmentalize cellular processes, as signaling molecules or as metabolic energy storage. Our current knowledge on lipid organization and cellular lipid homeostasis is mainly based on biochemical data. How

  11. Fluorescent lipid probes : some properties and applications (a review)

    NARCIS (Netherlands)

    Maier, O; Oberle, [No Value; Hoekstra, D

    2002-01-01

    Odd as it may seem, experimental challenges in lipid research are often hampered by the simplicity of the lipid structure. Since, as in protein research. mutants or overexpression of lipids are not realistic, a considerable amount of lipid research relies on the use Of tagged lipid analogues. Howeve

  12. Fluorescent lipid probes : some properties and applications (a review)

    NARCIS (Netherlands)

    Maier, O; Oberle, [No Value; Hoekstra, D

    Odd as it may seem, experimental challenges in lipid research are often hampered by the simplicity of the lipid structure. Since, as in protein research. mutants or overexpression of lipids are not realistic, a considerable amount of lipid research relies on the use Of tagged lipid analogues.

  13. [Nitric oxide and lipid peroxidation].

    Science.gov (United States)

    Cristol, J P; Maggi, M F; Guérin, M C; Torreilles, J; Descomps, B

    1995-01-01

    Nitric oxide (NO) is a free radical produced enzymatically in biological systems from the guanidino group of L-arginine. Its large spectrum of biological effects is achieved through chemical interactions with different targets including oxygen (O2), superoxide (O2o-) and other oxygen reactive species (ROS), transition metals and thiols. Superoxide anions and other ROS have been reported to react with NO to produce peroxynitrite anions that can decompose to form nitrogen dioxide (NO2) and hydroxyl radial (OHo). Thus, NO has been reported to have a dual effect on lipid peroxidation (prooxidant via the peroxynitrite or antioxydant via the chelation of ROS). In the present study we have investigated in different models the in vitro and in vivo action of NO on lipid peroxidation. Copper-induced LDL oxidation were used as an in vitro model. Human LDL (100 micrograms ApoB/ml) were incubated in oxygene-saturated PBS buffer in presence or absence of Cu2+ (2.5 microM) with increasing concentrations of NO donnors (sodium nitroprussiate or nitroso-glutathione). LDL oxidation was monitored continuously for conjugated diene formation (234 nm) and 4-hydroxynonenal (HNE) accumulation. Exogenous NO prevents in a dose dependent manner the progress of copper-induced oxidation. Ischaemia-reperfusion injury (I/R), characterized by an overproduction of ROS, is used as an in vivo model. Anaesthetized rats were submitted to 1 hour renal ischaemia following by 2 hours of reperfusion. Sham-operated rats (SOP) were used as control. Lipid peroxidation was evaluated by measuring the HNE accumulated in rats kidneys in presence or absence of L-arginine or D-arginine infusion. L-arginine, but not D-arginine, enhances HNE accumulation in I/R but not in SOP (< 0.050 pmol/g tissue in SOP versus 0.6 nmol/g tissue in I/R), showing that, in this experimental conditions, NO produced from L-arginine, enhances the toxicity of ROS. This study shows that the pro- or antioxydant effects of NO are different

  14. Study of the ion-channel behavior on glassy carbon electrode supported bilayer lipid membranes stimulated by perchlorate anion

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhiquan; Shi, Jun; Huang, Weimin, E-mail: huangwm@jlu.edu.cn

    2015-10-01

    In this paper, a kind of didodecyldimethylammonium bromide (DDAB) layer membranes was supported on a glassy carbon electrode (GCE). We studied the ion channel behavior of the supported bilayer lipid membrane by scanning electrochemical microscopy (SCEM) in tris(2,2′-bipyridine) ruthenium(II) solution. Perchlorate anion was used as a presence of stimulus and ruthenium(II) complex cations as the probing ions for the measurement of SECM, the lipid membrane channel was opened and exhibited the behavior of distinct SECM positive feedback curve. The channel was in a closed state in the absence of perchlorate anions while reflected the behavior of SECM negative feedback curve. The rates of electron transfer reaction in the lipid membranes surface were detected and it was dependant on the potential of SECM. - Highlights: • The rates of electron transfer reaction in the lipid membranes surface were detected. • Dynamic investigations of ion-channel behavior of supported bilayer lipid membranes by scanning electrochemical microscopy • A novel way to explore the interaction between molecules and supported bilayer lipid membranes.

  15. KADAR HbA1c DAN RASIO LIPID PADA WANITA DEWASA DENGAN OBESITAS SENTRAL

    Directory of Open Access Journals (Sweden)

    Lisa Sudaryanto

    2016-06-01

    Full Text Available Central obesity was accumulation of fat in the abdominal region. Many studies showed correlations between central obesity and cardiovascular diseases, e.g. diabetes and dyslipidemia.  This study was conducted to know the difference between HbA1c and lipid profil between the women with and without central obesity. This study was an analytic observational study with cross-sectional design. Subjects of 52 respondents were healthy adult women staff in campus I, II, III Sanata Dharma University in Yogyakarta and selected using purposive sampling technique. The data of waist circumference, pelvic/hip circumference, HbA1c and lipid profile were collected among the subjects and analyzed with computer with 95% confidence interval. The results of this study showed HbA1c levels and lipid profile were different between the women with and without central obesity, although the difference was not statistically significant.

  16. Should we individualize lipid profiling in women with polycystic ovary syndrome?

    DEFF Research Database (Denmark)

    Sundström Poromaa, Inger; Mellembakken, Jan Roar; Papunen, Laure Morin;

    2016-01-01

    STUDY QUESTION: Is it necessary to monitor lipid profiles in all young women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Lipid profiling is required when women with PCOS develop type 2 diabetes (T2D) or hypertension, but rarely changes clinical care before the age of 35 years. WHAT......, treatment level was guided by the European Society of Cardiology and the European Atherosclerosis Society Task Force for the management of dyslipidaemias. Change in clinical care was defined as need to (i) immediately start statin treatment or (ii) consider statin treatment if life-style intervention fails...... with hypertension was 42/57 (73.7%). In PCOS women who had not yet developed T2D or hypertension, lipid profiling only changed clinical care in 28 (2.3%). This number was further reduced to 12 (1.2%) in women below the age of 35 years, and to zero in normal-weight women below the age of 35 years. LIMITATIONS...

  17. Anandamide and analogous endocannabinoids: a lipid self-assembly study

    Energy Technology Data Exchange (ETDEWEB)

    Sagnella, Sharon M.; Conn, Charlotte E.; Krodkiewska, Irena; Mulet, Xavier; Drummond, Calum J.

    2014-09-24

    Anandamide, the endogenous agonist of the cannabinoid receptors, has been widely studied for its interesting biological and medicinal properties and is recognized as a highly significant lipid signaling molecule within the nervous system. Few studies have, however, examined the effect of the physical conformation of anandamide on its function. The study presented herein has focused on characterizing the self-assembly behaviour of anandamide and four other endocannabinoid analogues of anandamide, viz., 2-arachidonyl glycerol, arachidonyl dopamine, 2-arachidonyl glycerol ether (noladin ether), and o-arachidonyl ethanolamide (virodhamine). Molecular modeling of the five endocannabinoid lipids indicates that the highly unsaturated arachidonyl chain has a preference for a U or J shaped conformation. Thermal phase studies of the neat amphiphiles showed that a glass transition was observed for all of the endocannabinoids at {approx} -110 C with the exception of anandamide, with a second glass transition occurring for 2-arachidonyl glycerol, 2-arachidonyl glycerol ether, and virodhamine (-86 C, -95 C, -46 C respectively). Both anandamide and arachidonyl dopamine displayed a crystal-isotropic melting point (-4.8 and -20.4 C respectively), while a liquid crystal-isotropic melting transition was seen for 2-arachidonyl glycerol (-40.7 C) and 2-arachidonyl glycerol ether (-71.2 C). No additional transitions were observed for virodhamine. Small angle X-ray scattering and cross polarized optical microscopy studies as a function of temperature indicated that in the presence of excess water, both 2-arachidonyl glycerol and anandamide form co-existing Q{sub II}{sup G} (gyroid) and Q{sub II}{sup D} (diamond) bicontinuous cubic phases from 0 C to 20 C, which are kinetically stable over a period of weeks but may not represent true thermodynamic equilibrium. Similarly, 2-arachidonyl glycerol ether acquired an inverse hexagonal (HII) phase in excess water from 0 C to 40 C, while

  18. Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy

    Directory of Open Access Journals (Sweden)

    Schaffran T

    2014-07-01

    Full Text Available Tanja Schaffran,1 Nan Jiang,1 Markus Bergmann,2,3 Ekkehard Küstermann,4 Regine Süss,5 Rolf Schubert,5 Franz M Wagner,6 Doaa Awad,7 Detlef Gabel1,2,8 1Department of Chemistry, University of Bremen, 2Institute of Neuropathology, Klinikum Bremen-Mitte; 3Cooperative Center Medicine, University of Bremen, 4“In-vivo-MR” AG, FB2, University of Bremen, Bremen, 5Pharmaceutical Technology, University of Freiburg, Freiburg im Breisgau, 6Forschungsneutronenquelle Heinz Maier-Leibnitz (FRM II, Technische Unversitaet Muenchen, Garching, Germany; 7Department of Biochemistry, Alexandria University, Alexandria, Egypt; 8School of Engineering and Science, Jacobs University Bremen, Bremen, Germany Abstract: The potential of boron-containing lipids with three different structures, which were intended for use in boron neutron capture therapy, was investigated. All three types of boron lipids contained the anionic dodecaborate cluster as the headgroup. Their effects on two different tumor models in mice following intravenous injection were tested; for this, liposomes with boron lipid, distearoyl phosphatidylcholine, and cholesterol as helper lipids, and containing a polyethylene glycol lipid for steric protection, were administered intravenously into tumor-bearing mice (C3H mice for SCCVII squamous cell carcinoma and BALB/c mice for CT26/WT colon carcinoma. With the exception of one lipid (B-THF-14, the lipids were well tolerated, and no other animal was lost due to systemic toxicity. The lipid which led to death was not found to be much more toxic in cell culture than the other boron lipids. All of the lipids that were well tolerated showed hemorrhage in both tumor models within a few hours after administration. The hemorrhage could be seen by in vivo magnetic resonance and histology, and was found to occur within a few hours. The degree of hemorrhage depended on the amount of boron administered and on the tumor model. The observed unwanted effect of the lipids

  19. Intravenous lipid emulsion in clinical toxicology

    Directory of Open Access Journals (Sweden)

    Oswald Sarah

    2010-10-01

    Full Text Available Abstract Intravenous lipid emulsion is an established, effective treatment for local anesthetic-induced cardiovascular collapse. The predominant theory for its mechanism of action is that by creating an expanded, intravascular lipid phase, equilibria are established that drive the offending drug from target tissues into the newly formed 'lipid sink'. Based on this hypothesis, lipid emulsion has been considered a candidate for generic reversal of toxicity caused by overdose of any lipophilic drug. Recent case reports of successful resuscitation suggest the efficacy of lipid emulsion infusion for treating non-local anesthetic overdoses across a wide spectrum of drugs: beta blockers, calcium channel blockers, parasiticides, herbicides and several varieties of psychotropic agents. Lipid emulsion therapy is gaining acceptance in emergency rooms and other critical care settings as a possible treatment for lipophilic drug toxicity. While protocols exist for administration of lipid emulsion in the setting of local anesthetic toxicity, no optimal regimen has been established for treatment of acute non-local anesthetic poisonings. Future studies will shape the evolving recommendations for lipid emulsion in the setting of non-local anesthetic drug overdose.

  20. Stratum Corneum Barrier Lipids in Cholesteatoma

    DEFF Research Database (Denmark)

    Svane-Knudsen, V; Halkier-Sørensen, L; Rasmussen, G

    2000-01-01

    emerged. When the corneocyte reaches the transitional stage to the stratum corneum, the Odland bodies accumulate near the cell membrane and discharge their contents of lipid and enzymes. The lipids are reorganized into multiple long sheets of lamellar structures that embrace the keratinized corneocytes...

  1. Lipids of the living coelacanth, Latimeria chalumnae.

    Science.gov (United States)

    Nevenzel, J C; Rodegker, W; Mead, J F; Gordon, M S

    1966-06-24

    The muscle of Latimeria chalumnae contains 30 to 71 percent (dry weight) of lipid deposited extracellularly. Wax esters constituted 90 percent or more of the lipids from muscle and fat storage tissues. These esters, by gaschromatographic analysis, consisted of C(30) to C(40) homologs with one or two double bonds.

  2. Amylose folding under the influence of lipids

    NARCIS (Netherlands)

    Lopez, Cesar A.; de Vries, Alex H.; Marrink, Siewert J.

    2012-01-01

    The molecular dynamics simulation technique was used to study the folding and complexation process of a short amylose fragment in the presence of lipids. In aqueous solution, the amylose chain remains as an extended left-handed helix. After the addition of lipids in the system, however, we observe s

  3. Transport and sorting of membrane lipids

    NARCIS (Netherlands)

    van Meer, G.|info:eu-repo/dai/nl/068570368

    1993-01-01

    The lipid composition of cellular membranes may seem unnecessarily complex. However, the lipid composition of each membrane is carefully regulated by local metabolism and specificity in transport, marking the functional significance for the cell. Recent research has revealed unexpected discoveries c

  4. Lateral pressure profiles in lipid monolayers

    NARCIS (Netherlands)

    Baoukina, Svetlana; Marrink, Siewert J.; Tieleman, D. Peter

    2010-01-01

    We have used molecular dynamics simulations with coarse-grained and atomistic models to study the lateral pressure profiles in lipid monolayers. We first consider simple oil/air and oil/water interfaces, and then proceed to lipid monolayers at air/water and oil/water interfaces. The results are qual

  5. A comprehensive classification system for lipids

    NARCIS (Netherlands)

    Fahy, E.; Subramaniam, S.; Brown, H.A.; Glass, C.K.; Merrill, A.H.; Murphy, R.C.; Raetz, C.R.H.; Russell, D.W.; Seyama, Y.; Shaw, W.; Shimizu, T.; Spener, F.; van Meer, G.; VanNieuwenhze, M.S.; White, S.H.; Witztum, J.; Dennis, E.A.

    2005-01-01

    Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, and receptors. A comprehensive analysis of lipid molecules, “lipidomics,” in the context of genomics and proteomics is crucial to understanding cellular physiology and pathology; conseque

  6. The physics of stratum corneum lipid membranes.

    Science.gov (United States)

    Das, Chinmay; Olmsted, Peter D

    2016-07-28

    The stratum corneum (SC), the outermost layer of skin, comprises rigid corneocytes (keratin-filled dead cells) in a specialized lipid matrix. The continuous lipid matrix provides the main barrier against uncontrolled water loss and invasion of external pathogens. Unlike all other biological lipid membranes (such as intracellular organelles and plasma membranes), molecules in the SC lipid matrix show small hydrophilic groups and large variability in the length of the alkyl tails and in the numbers and positions of groups that are capable of forming hydrogen bonds. Molecular simulations provide a route for systematically probing the effects of each of these differences separately. In this article, we present the results from atomistic molecular dynamics of selected lipid bilayers and multi-layers to probe the effect of these polydispersities. We address the nature of the tail packing in the gel-like phase, the hydrogen bond network among head groups, the bending moduli expected for leaflets comprising SC lipids and the conformation of very long ceramide lipids in multi-bilayer lipid assemblies.This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'.

  7. Chemically Stable Lipids for Membrane Protein Crystallization

    Energy Technology Data Exchange (ETDEWEB)

    Ishchenko, Andrii; Peng, Lingling; Zinovev, Egor; Vlasov, Alexey; Lee, Sung Chang; Kuklin, Alexander; Mishin, Alexey; Borshchevskiy, Valentin; Zhang, Qinghai; Cherezov, Vadim (MIPT); (USC); (Scripps)

    2017-05-01

    The lipidic cubic phase (LCP) has been widely recognized as a promising membrane-mimicking matrix for biophysical studies of membrane proteins and their crystallization in a lipidic environment. Application of this material to a wide variety of membrane proteins, however, is hindered due to a limited number of available host lipids, mostly monoacylglycerols (MAGs). Here, we designed, synthesized, and characterized a series of chemically stable lipids resistant to hydrolysis, with properties complementary to the widely used MAGs. In order to assess their potential to serve as host lipids for crystallization, we characterized the phase properties and lattice parameters of mesophases made of two most promising lipids at a variety of different conditions by polarized light microscopy and small-angle X-ray scattering. Both lipids showed remarkable chemical stability and an extended LCP region in the phase diagram covering a wide range of temperatures down to 4 °C. One of these lipids has been used for crystallization and structure determination of a prototypical membrane protein bacteriorhodopsin at 4 and 20 °C.

  8. NMR spectroscopy for assessing lipid oxidation

    Science.gov (United States)

    Although lipid oxidation involves a variety of chemical reactions to produce numerous substances, most of traditional methods assessing lipid oxidation measure only one kind of oxidation product. For this reason, in general, one indicator of oxidation is not enough to accurately describe the oxidati...

  9. Obstructive sleep apnea and lipid abnormalities

    Directory of Open Access Journals (Sweden)

    Dimitar Karkinski

    2017-01-01

    CONCLUSION:OSA and obesity are potent risk factors for dyslipidemias. OSA could play a significant role in worsening of lipid metabolism in non-obese patients. But in obese patients, the extra weight makes the metabolic changes of lipid metabolism, and the role of OSA is not that very important like in non-obese patients.

  10. Do lipids influence the allergic sensitization process?

    Science.gov (United States)

    Bublin, Merima; Eiwegger, Thomas; Breiteneder, Heimo

    2014-09-01

    Allergic sensitization is a multifactorial process that is not only influenced by the allergen and its biological function per se but also by other small molecular compounds, such as lipids, that are directly bound as ligands by the allergen or are present in the allergen source. Several members of major allergen families bind lipid ligands through hydrophobic cavities or electrostatic or hydrophobic interactions. These allergens include certain seed storage proteins, Bet v 1-like and nonspecific lipid transfer proteins from pollens and fruits, certain inhalant allergens from house dust mites and cockroaches, and lipocalins. Lipids from the pollen coat and furry animals and the so-called pollen-associated lipid mediators are codelivered with the allergens and can modulate the immune responses of predisposed subjects by interacting with the innate immune system and invariant natural killer T cells. In addition, lipids originating from bacterial members of the pollen microbiome contribute to the outcome of the sensitization process. Dietary lipids act as adjuvants and might skew the immune response toward a TH2-dominated phenotype. In addition, the association with lipids protects food allergens from gastrointestinal degradation and facilitates their uptake by intestinal cells. These findings will have a major influence on how allergic sensitization will be viewed and studied in the future.

  11. Lipid polarity and sorting in epithelial cells

    NARCIS (Netherlands)

    van Meer, G.; Simons, K.

    1988-01-01

    Apical and basolateral membrane domains of epithelial cell plasma membranes possess unique lipid compositions. The tight junction, the structure separating the two domains, forms a diffusion barrier for membrane components and thereby prevents intermixing of the two sets of lipids. The barrier appar

  12. Computational Modeling of Lipid Metabolism in Yeast

    Directory of Open Access Journals (Sweden)

    Vera Schützhold

    2016-09-01

    Full Text Available Lipid metabolism is essential for all major cell functions and has recently gained increasing attention in research and health studies. However, mathematical modeling by means of classical approaches such as stoichiometric networks and ordinary differential equation systems has not yet provided satisfactory insights, due to the complexity of lipid metabolism characterized by many different species with only slight differences and by promiscuous multifunctional enzymes.Here, we present a object-oriented stochastic model approach as a way to cope with the complex lipid metabolic network. While all lipid species are treated objects in the model, they can be modified by the respective converting reactions based on reaction rules, a hybrid method that integrates benefits of agent-based and classical stochastic simulation. This approach allows to follow the dynamics of all lipid species with different fatty acids, different degrees of saturation and different headgroups over time and to analyze the effect of parameter changes, potential mutations in the catalyzing enzymes or provision of different precursors. Applied to yeast metabolism during one cell cycle period, we could analyze the distribution of all lipids to the various membranes in time-dependent manner.The presented approach allows to efficiently treat the complexity of cellular lipid metabolism and to derive conclusions on the time- and location-dependent distributions of lipid species and their properties such as saturation. It is widely applicable, easily extendable and will provide further insights in healthy and diseased states of cell metabolism.

  13. Lipids in plant-microbe interactions.

    Science.gov (United States)

    Siebers, Meike; Brands, Mathias; Wewer, Vera; Duan, Yanjiao; Hölzl, Georg; Dörmann, Peter

    2016-09-01

    Bacteria and fungi can undergo symbiotic or pathogenic interactions with plants. Membrane lipids and lipid-derived molecules from the plant or the microbial organism play important roles during the infection process. For example, lipids (phospholipids, glycolipids, sphingolipids, sterol lipids) are involved in establishing the membrane interface between the two organisms. Furthermore, lipid-derived molecules are crucial for intracellular signaling in the plant cell, and lipids serve as signals during plant-microbial communication. These signal lipids include phosphatidic acid, diacylglycerol, lysophospholipids, and free fatty acids derived from phospholipase activity, apocarotenoids, and sphingolipid breakdown products such as ceramide, ceramide-phosphate, long chain base, and long chain base-phosphate. Fatty acids are the precursors for oxylipins, including jasmonic acid, and for azelaic acid, which together with glycerol-3-phosphate are crucial for the regulation of systemic acquired resistance. This article is part of a Special Issue titled "Plant Lipid Biology," guest editors Kent Chapman and Ivo Feussner. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Keratins and lipids in ethnic hair.

    Science.gov (United States)

    Cruz, C F; Fernandes, M M; Gomes, A C; Coderch, L; Martí, M; Méndez, S; Gales, L; Azoia, N G; Shimanovich, U; Cavaco-Paulo, A

    2013-06-01

    Human hair has an important and undeniable relevance in society due to its important role in visual appearance and social communication. Hair is mainly composed of structural proteins, mainly keratin and keratin associated proteins and lipids. Herein, we report a comprehensive study of the content and distribution of the lipids among ethnic hair, African, Asian and Caucasian hair. More interestingly, we also report the study of the interaction between those two main components of hair, specifically, the influence of the hair internal lipids in the structure of the hair keratin. This was achieved by the use of a complete set of analytical tools, such as thin layer chromatography-flame ionization detector, X-ray analysis, molecular dynamics simulation and confocal microscopy. The experimental results indicated different amounts of lipids on ethnic hair compositions and higher percentage of hair internal lipids in African hair. In this type of hair, the axial diffraction of keratin was not observed in X-ray analysis, but after hair lipids removal, the keratin returned to its typical packing arrangement. In molecular dynamic simulation, lipids were shown to intercalate dimers of keratin, changing its structure. From those results, we assume that keratin structure may be influenced by higher concentration of lipids in African hair. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  15. Penetration of lipid monolayers by psychoactive drugs

    NARCIS (Netherlands)

    Demel, R.A.; Deenen, L.L.M. van

    1966-01-01

    The ability of a number of psychoactive drugs to penetrate lipid monolayers of varying composition was examined, and the following observation were made: (1) The increase in surface pressure of a monomolecular film appeared to depend on the chemical nature of the lipid as well as on the initial film

  16. Functionality of lipids and lipid-protein interactions in cereal-derived food products

    Directory of Open Access Journals (Sweden)

    Marion Didier

    2003-01-01

    Full Text Available Lipids and especially cereal lipids play a significant role in the processing and quality of cereals and baked cereal foods (bread, biscuits and beverages (beer. Most of the physico-chemical mechanisms responsible for the lipid functionality has been investigated and recently the specific role of lipid-binding proteins, e.g. lipid transfer proteins and puroindolines, has been highlighted. The state of the researches performed in this field are briefly presented in this review and the data obtained until now show that new perspectives are opened in cereal breeding and processing for improving the quality of cereals and cereal products.

  17. Production and early preservation of lipid biomarkers in iron hot springs.

    Science.gov (United States)

    Parenteau, Mary N; Jahnke, Linda L; Farmer, Jack D; Cady, Sherry L

    2014-06-01

    The bicarbonate-buffered anoxic vent waters at Chocolate Pots hot springs in Yellowstone National Park are 51-54°C, pH 5.5-6.0, and are very high in dissolved Fe(II) at 5.8-5.9 mg/L. The aqueous Fe(II) is oxidized by a combination of biotic and abiotic mechanisms and precipitated as primary siliceous nanophase iron oxyhydroxides (ferrihydrite). Four distinct prokaryotic photosynthetic microbial mat types grow on top of these iron deposits. Lipids were used to characterize the community composition of the microbial mats, link source organisms to geologically significant biomarkers, and investigate how iron mineralization degrades the lipid signature of the community. The phospholipid and glycolipid fatty acid profiles of the highest-temperature mats indicate that they are dominated by cyanobacteria and green nonsulfur filamentous anoxygenic phototrophs (FAPs). Diagnostic lipid biomarkers of the cyanobacteria include midchain branched mono- and dimethylalkanes and, most notably, 2-methylbacteriohopanepolyol. Diagnostic lipid biomarkers of the FAPs (Chloroflexus and Roseiflexus spp.) include wax esters and a long-chain tri-unsaturated alkene. Surprisingly, the lipid biomarkers resisted the earliest stages of microbial degradation and diagenesis to survive in the iron oxides beneath the mats. Understanding the potential of particular sedimentary environments to capture and preserve fossil biosignatures is of vital importance in the selection of the best landing sites for future astrobiological missions to Mars. This study explores the nature of organic degradation processes in moderately thermal Fe(II)-rich groundwater springs--environmental conditions that have been previously identified as highly relevant for Mars exploration.

  18. Production and Early Preservation of Lipid Biomarkers in Iron Hot Springs

    Energy Technology Data Exchange (ETDEWEB)

    Parenteau, Mary N.; Jahnke, Linda L.; Farmer, Jack D.; Cady, Sherry L.

    2014-06-01

    The bicarbonate-buffered anoxic vent waters at Chocolate Pots hot springs in Yellowstone National Park are 51–54°C, pH 5.5–6.0, and are very high in dissolved Fe(II) at 5.8–5.9 mg/L. The aqueous Fe(II) is oxidized by a combination of biotic and abiotic mechanisms and precipitated as primary siliceous nanophase iron oxyhydroxides (ferrihydrite). Four distinct prokaryotic photosynthetic microbial mat types grow on top of these iron deposits. Lipids were used to characterize the community composition of the microbial mats, link source organisms to geologically significant biomarkers, and investigate how iron mineralization degrades the lipid signature of the community. The phospholipid and glycolipid fatty acid profiles of the highest-temperature mats indicate that they are dominated by cyanobacteria and green nonsulfur filamentous anoxygenic phototrophs (FAPs). Diagnostic lipid biomarkers of the cyanobacteria include midchain branched mono- and dimethylalkanes and, most notably, 2-methylbacteriohopanepolyol. Diagnostic lipid biomarkers of the FAPs (Chloroflexus and Roseiflexus spp.) include wax esters and a long-chain tri-unsaturated alkene. Surprisingly, the lipid biomarkers resisted the earliest stages of microbial degradation and diagenesis to survive in the iron oxides beneath the mats. Understanding the potential of particular sedimentary environments to capture and preserve fossil biosignatures is of vital importance in the selection of the best landing sites for future astrobiological missions to Mars. Finally, this study explores the nature of organic degradation processes in moderately thermal Fe(II)-rich groundwater springs—environmental conditions that have been previously identified as highly relevant for Mars exploration.

  19. Immunostimulatory lipid nanoparticles from herbal medicine.

    Science.gov (United States)

    Hasson, Tal H; Takaoka, Anna; de la Rica, Roberto; Matsui, Hiroshi; Smeureanu, Gabriela; Drain, Charles M; Kawamura, Akira

    2014-04-01

    Reproducibility is an important issue in biological characterization of drug candidates and natural products. It is not uncommon to encounter cases in which supposedly the same sample exhibits very different biological activities. During our characterization of macrophage-stimulatory lipids from herbal medicine, it was found that the potency of these lipids could vary substantially from experiment to experiment. Further analysis of this reproducibility issue led to the discovery of solvent-dependent nanoparticle formation by these lipids. While larger nanoparticles (approximately 100 nm) of these lipids showed modest macrophage-stimulatory activity, smaller nanoparticles (nanoparticle formation and macrophage-stimulatory activity of plant lipids. Although nanoparticles have been extensively studied in the context of vehicles for drug delivery, our finding indicates that drugs themselves can form nanoassemblies, and their biological properties may be altered by the way they assemble. © 2013 John Wiley & Sons A/S.

  20. Anaerobic lipid degradation through acidification and methanization.

    Science.gov (United States)

    Kim, Ijung; Kim, Sang-Hyoun; Shin, Hang-Sik; Jung, Jin-Young

    2010-01-01

    In biological wastewater treatment high lipid concentration is known to inhibit microorganisms and cause active biomass flotation. To reduce lipid inhibition, a two-phase anaerobic system, consisting of an anaerobic sequencing batch reactor (ASBR) and an upflow anaerobic sludge blanket (UASB) reactor, was applied to synthetic dairy wastewater. During 153 days of operation, the two-phase system showed stable performance in lipid degradation. In the ASBR, a 13% lipid removal efficiency and 10% double bond removal efficiency were maintained. In the UASB, the chemical oxygen demand (COD), lipid and volatile fatty acid (VFA) removal efficiencies were more than 80%, 70% and 95%, respectively, up to organic loading rate 6.5 g COD/L/day. There were no operational problems such as serious scum formation or sludge washout. Protein degradation occurred prior to degradation during acidogenesis.

  1. Insulin-induced lipid binding to hemoglobin

    Directory of Open Access Journals (Sweden)

    VESNA NIKETIC

    2003-01-01

    Full Text Available Under hypoglycemic conditions, concomitant hyperinsulinism causes an apparent modification of hemoglobin (Hb which is manifested by its aggregation (Niketi} et al., Clin. Chim. Acta 197 (1991 47. In the present work the causes and mechanisms underlying this Hb modification were studied. Hemoglobin isolated from normal erythrocytes incubated with insulin was analyzed by applying 31P-spectrometry and lipid extraction and analysis. To study the dynamics of the plasma membrane during hyperinsulinism, a fluorescent lipid-analog was applied. In the presence of insulin, phosphatidylserine (PS, phosphatidylethanolamine (PE and cholesterol were found to bind to Hb. Lipid binding resulted in Hb aggregation, a condition that can be reproduced when phospholipids are incubated with Hb in vitro. Using a fluorescent lipid-analog, it was also shown that exposing erythrocytes to supraphysiological concentrations of insulin in vitro resulted in the internalization of lipids. The results presented in this work may have relevance to cases of diabetes mellitus and hypoglycemia.

  2. [Germ cell membrane lipids in spermatogenesis].

    Science.gov (United States)

    Wang, Ting; Shi, Xiao; Quan, Song

    2016-05-01

    Spermatogenesis is a complex developmental process in which a diploid progenitor germ cell transforms into highly specialized spermatozoa. During spermatogenesis, membrane remodeling takes place, and cell membrane permeability and liquidity undergo phase-specific changes, which are all associated with the alteration of membrane lipids. Lipids are important components of the germ cell membrane, whose volume and ratio fluctuate in different phases of spermatogenesis. Abnormal lipid metabolism can cause spermatogenic dysfunction and consequently male infertility. Germ cell membrane lipids are mainly composed of cholesterol, phospholipids and glycolipids, which play critical roles in cell adhesion and signal transduction during spermatogenesis. An insight into the correlation of membrane lipids with spermatogenesis helps us to better understand the mechanisms of spermatogenesis and provide new approaches to the diagnosis and treatment of male infertility.

  3. Lipid protrusions membrane softness, and enzymatic activity

    DEFF Research Database (Denmark)

    Jensen, Morten Østergaard; Høyrup, P.; Callisen, T.H.;

    2004-01-01

    The activity of phospholipase A(2) on lipid bilayers displays a characteristic lag burst behavior that has previously been shown to reflect the physical properties of the substrate. It has remained unclear which underlying molecular mechanism is responsible for this phenomenon. We propose here...... that protrusions of single lipid molecules out of the bilayer plane could provide such a mechanism. The proposal is supported by a combination of atomic-scale molecular dynamics simulations, theory, and experiments that have been performed in order to investigate the relationship between on the one side lipid...... protrusion modes and mechanical softness of phospholipid bilayers and on the other side the activity of enzymes acting on lipid bilayers composed of different unsaturated lipids. Specifically, our experiments show a correlation between the bilayer bending rigidity and the apparent Arrhenius activation energy...

  4. Model parameters for simulation of physiological lipids

    Science.gov (United States)

    McGlinchey, Nicholas

    2016-01-01

    Coarse grain simulation of proteins in their physiological membrane environment can offer insight across timescales, but requires a comprehensive force field. Parameters are explored for multicomponent bilayers composed of unsaturated lipids DOPC and DOPE, mixed‐chain saturation POPC and POPE, and anionic lipids found in bacteria: POPG and cardiolipin. A nonbond representation obtained from multiscale force matching is adapted for these lipids and combined with an improved bonding description of cholesterol. Equilibrating the area per lipid yields robust bilayer simulations and properties for common lipid mixtures with the exception of pure DOPE, which has a known tendency to form nonlamellar phase. The models maintain consistency with an existing lipid–protein interaction model, making the force field of general utility for studying membrane proteins in physiologically representative bilayers. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. PMID:26864972

  5. Molecular restructuring of water and lipids upon the interaction of DNA with lipid monolayers.

    Science.gov (United States)

    Campen, R Kramer; Ngo, Thuy T M; Sovago, Maria; Ruysschaert, Jean-Marie; Bonn, Mischa

    2010-06-16

    Understanding the molecular mechanism of DNA/lipid interaction is critical in optimizing the use of lipid cofactors in gene therapy. Here, we address this question by employing label-free vibrational sum frequency (VSF) spectroscopy to study the interaction of DNA with lipid monolayers of the cationic lipids DPTAP(1,2-dipalmitoyl-3-trimethylammonium-propane) and diC14-amidine as well as the zwitterionic lipid DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) in the presence and absence of calcium. Our approach has the advantage both of allowing us to explicitly probe intermolecular interactions and of providing insight into the structure of water and lipids around DNA at the lipid interface. We find, by examination of the OD stretch of interfacial D(2)O, that water structure differs markedly between systems containing DNA adsorbed to cationic and those that contain DNA adsorbed to zwitterionic lipid monolayers (in the presence or absence of Ca(2+)). The spectral response of interfacial water in the cationic system is consistent with a highly structured, undercoordinated, structural 'type' of water. Further, by investigation of CH stretch modes of the diC14-amidine lipid tails, we demonstrate that the adsorption of DNA to this lipid leads to increased ordering of lipid tails.

  6. Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids.

    Science.gov (United States)

    Cruz-Garcia, Lourdes; Schlegel, Amnon

    2014-09-01

    Liver X receptors (Lxrs) are master regulators of cholesterol catabolism, driving the elimination of cholesterol from the periphery to the lumen of the intestine. Development of pharmacological agents to activate Lxrs has been hindered by synthetic Lxr agonists' induction of hepatic lipogenesis and hypertriglyceridemia. Elucidating the function of Lxrs in regulating enterocyte lipid handling might identify novel aspects of lipid metabolism that are pharmacologically amenable. We took a genetic approach centered on the single Lxr gene nr1h3 in zebrafish to study the role of Lxr in enterocyte lipid metabolism. Loss of nr1h3 function causes anticipated gene regulatory changes and cholesterol intolerance, collectively reflecting high evolutionary conservation of zebrafish Lxra function. Intestinal nr1h3 activation delays transport of absorbed neutral lipids, with accumulation of neutral lipids in enterocyte cytoplasmic droplets. This delay in transport of ingested neutral lipids protects animals from hypercholesterolemia and hepatic steatosis induced by a high-fat diet. On a gene regulatory level, Lxra induces expression of acsl3a, which encodes acyl-CoA synthetase long-chain family member 3a, a lipid droplet-anchored protein that directs fatty acyl chains into lipids. Forced overexpression of acls3a in enterocytes delays, in part, the appearance of neutral lipids in the vasculature of zebrafish larvae. Activation of Lxr in the intestine cell-autonomously regulates the rate of delivery of absorbed lipids by inducting a temporary lipid intestinal droplet storage depot.

  7. Effect of tension and curvature on the chemical potential of lipids in lipid aggregates.

    Science.gov (United States)

    Grafmüller, Andrea; Lipowsky, Reinhard; Knecht, Volker

    2013-01-21

    Understanding the factors that influence the free energy of lipids in bilayer membranes is an essential step toward understanding exchange processes of lipids between membranes. In general, both lipid composition and membrane geometry can affect lipid exchange rates between bilayer membranes. Here, the free energy change ΔG(des) for the desorption of dipalmitoyl-phosphatidylcholine (DPPC) lipids from different lipid aggregates has been computed using molecular dynamics simulations and umbrella sampling. The value of ΔG(des) is found to depend strongly on the local properties of the aggregate, in that both tension and curvature lead to an increase in ΔG(des). A detailed analysis shows that the increased desorption free energy for tense bilayers arises from the increased conformational entropy of the lipid tails, which reduces the favorable component -TΔS(L) of the desorption free energy.

  8. Method of fabricating lipid bilayer membranes on solid supports

    Science.gov (United States)

    Cho, Nam-Joon (Inventor); Frank, Curtis W. (Inventor); Glenn, Jeffrey S. (Inventor); Cheong, Kwang Ho (Inventor)

    2012-01-01

    The present invention provides a method of producing a planar lipid bilayer on a solid support. With this method, a solution of lipid vesicles is first deposited on the solid support. Next, the lipid vesicles are destabilized by adding an amphipathic peptide solution to the lipid vesicle solution. This destabilization leads to production of a planar lipid bilayer on the solid support. The present invention also provides a supported planar lipid bilayer, where the planar lipid bilayer is made of naturally occurring lipids and the solid support is made of unmodified gold or titanium oxide. Preferably, the supported planar lipid bilayer is continuous. The planar lipid bilayer may be made of any naturally occurring lipid or mixture of lipids, including, but not limited to phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinsitol, cardiolipin, cholesterol, and sphingomyelin.

  9. 2011 Plant Lipids: Structure, Metabolism, & Function Gordon Research Conference

    Energy Technology Data Exchange (ETDEWEB)

    Christopher Benning

    2011-02-04

    This is the second Gordon Research Conference on 'Plant Lipids: Structure, Metabolism & Function'. It covers current topics in lipid structure, metabolism and function in eukaryotic photosynthetic organisms including seed plants, algae, mosses and ferns. Work in photosynthetic bacteria is considered as well as it serves the understanding of specific aspects of lipid metabolism in plants. Breakthroughs are discussed in research on plant lipids as diverse as glycerolipids, sphingolipids, lipids of the cell surface, isoprenoids, fatty acids and their derivatives. The program covers nine concepts at the forefront of research under which afore mentioned plant lipid classes are discussed. The goal is to integrate areas such as lipid signaling, basic lipid metabolism, membrane function, lipid analysis, and lipid engineering to achieve a high level of stimulating interaction among diverse researchers with interests in plant lipids. One Emphasis is on the dynamics and regulation of lipid metabolism during plant cell development and in response to environmental factors.

  10. Plasma lipids profile and erythrocytes system in patients with coronary heart disease

    Science.gov (United States)

    Malinova, Lidia I.; Simonenko, Georgy V.; Tuchin, Valery V.; Denisova, Tatyana P.

    2006-08-01

    Erythrocytes system study can provide a framework for detailed exploration of blood cell-cell and cell-vessel wall interactions, one of the key patterns in blood and vascular pathophysiology. Our objective was to explore erythrocytes system in patients with stable angina pectoris II f.c. (Canadian classification). The participants (N = 56, age 40 - 55 years) without obesity, glucose tolerance violations, lipid lowering drugs treating, heart failure of II and more functional classes (NYHA), coronary episode at least 6 months before study were involved in the study. Blood samples were incubated with glucose solutions of increasing concentrations (from 2.5% to 20% with 2.5% step) during 60 mm (36° C). In prepared blood smears erythrocyte's sizes were studied. Plasma total cholesterol, triglyceride and glucose levels were also measured. Received data were approximated by polynomials of high degree, with after going first and second derivations. Erythrocytes system "behavior" was studied by means of phase pattern constructing. By lipids levels all the patient were divided into five groups: 1) patients with normal lipids levels, 2) patients with borderline total cholesterol level, 3) patients with isolated hypercholesterolemia, 4) patients with isolated hypertriglyceridemia and 5) patients with combined hyperlipidemia. Erythrocytes size lowering process was of set of "stages", which characteristics differ significantly (p > 0.05) in all five groups. Their rate and acceleration characteristics allow us to detect type of lipid profile in patients. Erythrocyte system disturbing by glucose concentration increase show to be most resistant in group of patients with isolated hypercholesterolemia.

  11. The action of polyene antibiotics on lipid bilayer membranes in the presence of several cations and anions

    NARCIS (Netherlands)

    Zutphen, H. van; Demel, R.A.; Norman, A.W.; Deenen, L.L.M. van

    1971-01-01

    1. 1. Filipin complex, filipin II, filipin III, nystatin, etruscomycin, and pimaricin at concentrations of 10−5 M were able to disrupt bimolecular lipid films containing lecithin and cholesterol in a 1:1 molar ratio. 2. 2. The above antibiotics were not able to disrupt lecithin bilayer

  12. The structural role of cholesterol in cell membranes: from condensed bilayers to lipid rafts.

    Science.gov (United States)

    Krause, Martin R; Regen, Steven L

    2014-12-16

    CONSPECTUS: Defining the two-dimensional structure of cell membranes represents one of the most daunting challenges currently facing chemists, biochemists, and biophysicists. In particular, the time-averaged lateral organization of the lipids and proteins that make up these natural enclosures has yet to be established. As the classic Singer-Nicolson model of cell membranes has evolved over the past 40 years, special attention has focused on the structural role played by cholesterol, a key component that represents ca. 30% of the total lipids that are present. Despite extensive studies with model membranes, two fundamental issues have remained a mystery: (i) the mechanism by which cholesterol condenses low-melting lipids by uncoiling their acyl chains and (ii) the thermodynamics of the interaction between cholesterol and high- and low-melting lipids. The latter bears directly on one of the most popular notions in modern cell biology, that is, the lipid raft hypothesis, whereby cholesterol is thought to combine with high-melting lipids to form "lipid rafts" that float in a "sea" of low-melting lipids. In this Account, we first describe a chemical approach that we have developed in our laboratories that has allowed us to quantify the interactions between exchangeable mimics of cholesterol and low- and high-melting lipids in model membranes. In essence, this "nearest-neighbor recognition" (NNR) method involves the synthesis of dimeric forms of these lipids that contain a disulfide moiety as a linker. By means of thiolate-disulfide interchange reactions, equilibrium mixtures of dimers are then formed. These exchange reactions are initiated either by adding dithiothreitol to a liposomal dispersion to generate a small amount of thiol monomer or by including a small amount of thiol monomer in the liposomes at pH 5.0 and then raising the pH to 7.4. We then show how such NNR measurements have allowed us to distinguish between two very different mechanisms that have been

  13. Hepatic lipid characteristics and histopathology of laying hens fed CLA or n-3 fatty acids.

    Science.gov (United States)

    Cherian, Gita; Goeger, Mary P

    2004-01-01

    The effect of dietary CLA and n-3 PUFA on hepatic TAG accumulation, histopathology, and FA incorporation in lipid classes by laying chickens was investigated. One hundred twenty 30-wk-old single comb white leghorn laying hens were distributed randomly to four treatments (3 replications of 10 birds) and were fed diets containing CLA and animal fat (Diet I), 18:3n-3 (Diet II), or long-chain n-3 FA (Diet III). A sunflower oil (n-6 FA)-based diet vvas the control. Feeding Diet I resulted in an increase in hepatic total lipids (P < 0.05). The liver TAG content was 32.2, 18.9, 29.4, and 18.7 mg/g for hens fed Diet I, Diet II, Diet III, and the control diet, respectively (P< 0.05). The serum TAG was lowest in birds fed Diet II (P < 0.05). Diet I resulted in an increase in the total number of fat vacuoles and lipid infiltration in hepatocytes (P < 0.05). The number of cells with 75% or higher lipid vacuolation was observed only in birds fed Diet I. Feeding diets containing CLA resulted in an increase in the content of the c9,t11 CLA isomer in liver TAG and PC (P < 0.05). No difference was observed in the CLA concentration of hepatic PE fractions. The content of DHA (22:6n-3) was higher in the TAG, PC, and PE of hens fed Diet II and Diet III than Diet I and the control (P < 0.05). Feeding CLA resulted in an increase in total saturated FA in the TAG and PC fractions (P < 0.05). Long-term feeding of CLA in laying birds leads to an increase in liver TAG and may predispose birds to fatty liver hemorrhagic syndrome.

  14. Triglyceride Blisters in Lipid Bilayers: Implications for Lipid Droplet Biogenesis and the Mobile Lipid Signal in Cancer Cell Membranes

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Duelund, Lars; Pakkanen, Kirsi Inkeri

    2010-01-01

    Triglycerides have a limited solubility, around 3%, in phosphatidylcholine lipid bilayers. Using millisecond-scale course grained molecular dynamics simulations, we show that the model lipid bilayer can accommodate a higher concentration of triolein (TO) than earlier anticipated, by sequestering...... aggregates of unknown function present in malignant cells, and to the early biogenesis of lipid droplets accommodated between the two leaflets of the endoplasmic reticulum membrane. The TO aggregates give the bilayer a blister-like appearance, and will hinder the formation of multi-lamellar phases in model...

  15. Obesity alters the gustatory perception of lipids in the mouse: plausible involvement of lingual CD36[S

    Science.gov (United States)

    Chevrot, Michael; Bernard, Arnaud; Ancel, Déborah; Buttet, Marjorie; Martin, Céline; Abdoul-Azize, Souleymane; Merlin, Jean-François; Poirier, Hélène; Niot, Isabelle; Khan, Naim Akhtar; Passilly-Degrace, Patricia; Besnard, Philippe

    2013-01-01

    A relationship between orosensory detection of dietary lipids, regulation of fat intake, and body mass index was recently suggested. However, involved mechanisms are poorly understood. Moreover, whether obesity can directly modulate preference for fatty foods remains unknown. To address this question, exploration of the oral lipid sensing system was undertaken in diet-induced obese (DIO) mice. By using a combination of biochemical, physiological, and behavioral approaches, we found that i) the attraction for lipids is decreased in obese mice, ii) this behavioral change has an orosensory origin, iii) it is reversed in calorie-restricted DIO mice, revealing an inverse correlation between fat preference and adipose tissue size, iv) obesity suppresses the lipid-mediated downregulation of the lipid-sensor CD36 in circumvallate papillae, usually found during the refeeding of lean mice, and v) the CD36-dependent signaling cascade controlling the intracellular calcium levels ([Ca2+]i) in taste bud cells is decreased in obese mice. Therefore, obesity alters the lipid-sensing system responsible for the oral perception of dietary lipids. This phenomenon seems to take place through a CD36-mediated mechanism, leading to changes in eating behavior. PMID:23840049

  16. Stratification of archaeal membrane lipids in the ocean and implications for adaptation and chemotaxonomy of planktonic archaea.

    Science.gov (United States)

    Zhu, Chun; Wakeham, Stuart G; Elling, Felix J; Basse, Andreas; Mollenhauer, Gesine; Versteegh, Gerard J M; Könneke, Martin; Hinrichs, Kai-Uwe

    2016-12-01

    Membrane lipids of marine planktonic archaea have provided unique insights into archaeal ecology and paleoceanography. However, past studies of archaeal lipids in suspended particulate matter (SPM) and sediments mainly focused on a small class of fully saturated glycerol dibiphytanyl glycerol tetraether (GDGT) homologues identified decades ago. The apparent low structural diversity of GDGTs is in strong contrast to the high diversity of metabolism and taxonomy among planktonic archaea. Furthermore, adaptation of archaeal lipids in the deep ocean remains poorly constrained. We report the archaeal lipidome in SPM from diverse oceanic regimes. We extend the known inventory of planktonic archaeal lipids to include numerous unsaturated archaeal ether lipids (uns-AELs). We further reveal (i) different thermal regulations and polar headgroup compositions of membrane lipids between the epipelagic (≤ 100 m) and deep (>100 m) populations of archaea, (ii) stratification of unsaturated GDGTs with varying redox conditions, and (iii) enrichment of tetra-unsaturated archaeol and fully saturated GDGTs in epipelagic and deep oxygenated waters, respectively. Such stratified lipid patterns are consistent with the typical distribution of archaeal phylotypes in marine environments. We, thus, provide an ecological context for GDGT-based paleoclimatology and bring about the potential use of uns-AELs as biomarkers for planktonic Euryarchaeota. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  17. Speciation of lipids and humus-like colloidal compounds in a forest soil reclaimed with municipal solid waste compost.

    Science.gov (United States)

    Zancada, M Cristina; Almendros, Gonzalo; Sanz, Jesús; Román, Román

    2004-02-01

    The progressive transformations of lipid and humus-like fractions in soil after massive input (400 Mg ha(-1)) of urban waste have been studied during an 87-week experiment in field plots of a degraded Calcic Regosol in Central Spain. Structural changes in the macromolecular fractions were small when compared with the qualitative and quantitative changes in lipid composition. The intense depletion of the lipid fraction with time and the decrease of the humic acid to fulvic acid ratio were the most significant quantitative indices of the compost transformation in soil. Changes in soil lipid fractions were especially noted in relation to their speciation status and distribution patterns (carbon preference index and relative chain length). Three subfractions were considered: (I) direct extraction with petroleum ether, (II) liquid-liquid extraction after soil treatment with 2 M H3PO4 and (III) after soil treatment with 0.1 M NaOH. Although lipid concentration tends to decrease with time, lipids in the fraction tightly bonded to soil (III) remained qualitatively and quantitatively constant in the course of the field experiment. Gas chromatographic-mass spectrometric analyses showed that the more stable the association of lipid to the soil matrix, the fewer the changes observed in the distribution pattern of the fatty acids during the progressive transformation stages.

  18. Hydrogel Micro-/Nanosphere Coated by a Lipid Bilayer: Preparation and Microscopic Probing

    Directory of Open Access Journals (Sweden)

    Sarah Rahni

    2017-02-01

    Full Text Available The result of polymeric nanogels and lipid vesicles interaction—lipobeads—can be considered as multipurpose containers for future therapeutic applications, such as targeted anticancer chemotherapy with superior tumor response and minimum side effects. In this work, micrometer sized lipobeads were synthesized by two methods: (i mixing separately prepared microgels made of poly(N-isopropylacrylamide (PNIPA and phospholipid vesicles of micrometer or nanometer size and (ii polymerization within the lipid vesicles. For the first time, a high vacuum scanning electron microscopy was shown to be suitable for a quick validation of the structural organization of wet lipobeads and their constituents without special sample preparation. In particular, the structural difference of microgels prepared by thermal and UV-polymerization in different solvents was revealed and three types of giant liposomes were recognized under high vacuum in conjunction with their size, composition, and method of preparation. Importantly, the substructure of the hydrogel core and multi- and unilamellar constructions of the peripheral lipid part were explicitly distinguished on the SEM images of lipobeads, justifying the spontaneous formation of a lipid bilayer on the surface of microgels and evidencing an energetically favorable structural organization of the hydrogel/lipid bilayer assembly. This key property can facilitate lipobeads’ preparation and decrease technological expenses on their scaled production. The comparison of the SEM imaging with the scanning confocal and atomic force microscopies data are also presented in the discussion.

  19. Taste masked lipid pellets with enhanced release of hydrophobic active ingredient.

    Science.gov (United States)

    Vaassen, Jonathan; Bartscher, Kathrin; Breitkreutz, Joerg

    2012-06-15

    Solid lipid extrusion is a suitable technique to produce oral dosage forms with improved taste properties. The design of a lipid formulation for poorly water soluble drugs is a challenge because of the poor dissolution and potential bioavailability problems. In this study, solid lipid extrusion at room temperature was applied for the formulation development of the BCS Class II drug NXP 1210. Powdered hard fat (Witocan(®) 42/44 mikrofein), glycerol distearate (Precirol(®) ato 5) and glycerol trimyristate (Dynasan(®) 114) were investigated as lipid binders. Different amounts of polyvinylalcohol (PVA)-polyethyleneglycol (PEG)-graft copolymer (Kollicoat(®) IR) and crospovidone (Polyplasdone(®) Xl-10) were scrutinized as solubilizers. The dissolution profiles depicted a short lag time (about 2min) and then fast and complete dissolution of NXP 1210 by increasing the amount of crospovidone. The initial release was more delayed with an increased amount of PVA-PEG-graft copolymer. Dissolution rate could also be influenced by changing the lipid binder from pure hard fat into a mixture of hard fat, glycerol distearate and glycerol trimyristate. The formulations are feasible for taste-masked granules or pellets containing poorly soluble drugs.

  20. Metabolic response to lipid infusion in fasting winter-acclimatized king penguin chicks (Aptenodytes patagonicus).

    Science.gov (United States)

    Teulier, Loïc; Tornos, Jérémy; Rouanet, Jean-Louis; Rey, Benjamin; Roussel, Damien

    2013-05-01

    During the cold austral winter, king penguin chicks are infrequently fed by their parents and thus experience severe nutritional deprivation under harsh environmental conditions. These energetic constraints lead to a range of energy sparing mechanisms balanced by the maintenance of efficient thermogenic processes. The present work investigated whether the high thermogenic capacities exhibited by winter-acclimatized king penguin chicks could be related to an increase in lipid substrate supply and oxidation in skeletal muscle, the main site of thermogenesis in birds. To test this hypothesis, we examined i) the effect of an experimental rise in plasma triglyceride on the whole metabolic rate in winter-acclimatized (WA) and de-acclimatized king penguin chicks kept at thermoneutrality (TN), and ii) investigated the fuel preference of muscle mitochondria. In vivo, a perfusion of a lipid emulsion induced a small 10% increase of metabolic rate in WA chicks but not in TN group. In vitro, the oxidation rate of muscle mitochondria respiring on lipid-derived substrate was +40% higher in WA chicks than in TN, while no differences were found between groups when mitochondria oxidized carbohydrate-derived substrate or succinate. Despite an enhanced fuel selection towards lipid oxidation in skeletal muscle, a rise of circulating lipids per se was not sufficient to fully unravel the thermogenic capacity of winter-acclimatized king penguin chicks.

  1. Beyond liposomes: Recent advances on lipid based nanostructures for poorly soluble/poorly permeable drug delivery.

    Science.gov (United States)

    Teixeira, M C; Carbone, C; Souto, E B

    2017-08-01

    Solid lipid nanoparticle (SLN), nanostructured lipid carriers (NLC) and hybrid nanoparticles, have gained increasing interest as drug delivery systems because of their potential to load and release drugs from the Biopharmaceutical classification system (BCS) of class II (low solubility and high permeability) and of class IV (low solubility and low permeability). Lipid properties (e.g. high solubilizing potential, biocompatibility, biotolerability, biodegradability and distinct route of absorption) contribute for the improvement of the bioavailability of these drugs for a set of administration routes. Their interest continues to grow, as translated by the number of patents being field worldwide. This paper discusses the recent advances on the use of SLN, NLC and lipid-polymer hybrid nanoparticles for the loading of lipophilic, poorly water-soluble and poorly permeable drugs, being developed for oral, topical, parenteral and ocular administration, also discussing the industrial applications of these systems. A review of the patents filled between 2014 and 2017, concerning the original inventions of lipid nanocarriers, is also provided. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Interfacial & colloidal aspects of lipid digestion.

    Science.gov (United States)

    Wilde, P J; Chu, B S

    2011-06-09

    Amongst the main issues challenging the food manufacturing sector, health and nutrition are becoming increasingly important. Global concerns such as obesity, the ageing population and food security will have to be addressed. Food security is not just about assuring food supply, but is also about optimising nutritional delivery from the food that is available [1]. Therefore one challenge is to optimise the health benefits from the lipids and lipid soluble nutrients. Colloid scientists have an affinity for lipids because they are water insoluble, however this presents a challenge to the digestive system, which has to convert them to structures that are less insoluble so they are available for uptake. Despite this, the human digestive system is remarkably effective at digesting and absorbing most lipids. This is primarily driven through maximising energy intake, as lipids possess the highest calorific value, which was a survival trait to survive times of famine, but is now an underlying cause of obesity in developed countries with high food availability. The critical region here is the lipid-water interface, where the key reactions take place to solubilise lipids and lipid soluble nutrients. Digestive lipases have to adsorb to the oil water interface in order to hydrolyse triacylglycerols into fatty acids and mono glycerides, which accumulate at the interface [2], and inhibit lipase activity. Pancreatic lipase, which is responsible for the majority of lipid hydrolysis, also requires the action of bile salts and colipase to function effectively. Bile salts both aid the adsorption of co-lipase and lipase, and help solubilise the lipolysis products which have accumulated at the interface, into mixed micelles composing bile salts and a range of other lipids, to facilitate transport to the gut mucosal surface prior to uptake and absorption. The process can be affected by the lipid type, as shorter chain, fatty acids are more easily absorbed, whereas the uptake of longer

  3. The lipid raft proteome of Borrelia burgdorferi.

    Science.gov (United States)

    Toledo, Alvaro; Pérez, Alberto; Coleman, James L; Benach, Jorge L

    2015-11-01

    Eukaryotic lipid rafts are membrane microdomains that have significant amounts of cholesterol and a selective set of proteins that have been associated with multiple biological functions. The Lyme disease agent, Borrelia burgdorferi, is one of an increasing number of bacterial pathogens that incorporates cholesterol onto its membrane, and form cholesterol glycolipid domains that possess all the hallmarks of eukaryotic lipid rafts. In this study, we isolated lipid rafts from cultured B. burgdorferi as a detergent resistant membrane (DRM) fraction on density gradients, and characterized those molecules that partitioned exclusively or are highly enriched in these domains. Cholesterol glycolipids, the previously known raft-associated lipoproteins OspA and OpsB, and cholera toxin partitioned into the lipid rafts fraction indicating compatibility with components of the DRM. The proteome of lipid rafts was analyzed by a combination of LC-MS/MS or MudPIT. Identified proteins were analyzed in silico for parameters that included localization, isoelectric point, molecular mass and biological function. The proteome provided a consistent pattern of lipoproteins, proteases and their substrates, sensing molecules and prokaryotic homologs of eukaryotic lipid rafts. This study provides the first analysis of a prokaryotic lipid raft and has relevance for the biology of Borrelia, other pathogenic bacteria, as well as for the evolution of these structures. All MS data have been deposited in the ProteomeXchange with identifier PXD002365 (http://proteomecentral.proteomexchange.org/dataset/PXD002365).

  4. Analysis of meibum and tear lipids.

    Science.gov (United States)

    Pucker, Andrew D; Nichols, Jason J

    2012-10-01

    The meibum is a lipid-rich secretion that is the primary component of the external layer of the tear film. The meibomian glands produce the meibum, and meibomian gland dysfunction can lead to degradation of the tear film. Such dysfunction can result in ocular irritation, inflammation, and clinical disease. Understanding this relationship is critical to preventing ocular disease; therefore, a search of peer-reviewed literature focusing on the collection, quantification, and analysis of normal and abnormal meibum and tear lipids was conducted. Numerous collection and quantification techniques are described, including their advantages and disadvantages. Studies indicate that the meibum and tear lipids consist of a large array of polar and nonpolar lipids; individual lipids or their classes can be correlated to pathology. Significant amounts of lipids are deposited on contact lenses, depending on the nature of their polymer chemistry. These findings taken together indicate that normal meibum and tear lipids are essential for normal ocular health. Additional studies are required to provide a better understanding of the meibum and tear film biomolecules so that more effective treatments for blepharitis, dry eye disease, and tear film-related contact lens complications can be devised.

  5. Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Chuan Junlan [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Li Yanzhen [Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery Technology and Pharmacokinetics (China); Yang Likai; Sun Xun [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Zhang Qiang [Peking University, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences (China); Gong Tao, E-mail: gongtaoy@126.com; Zhang Zhirong, E-mail: zrzzl@vip.sina.com [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China)

    2013-05-15

    The present study aimed at developing a drug delivery system targeting the densest site of tuberculosis infection, the alveolar macrophages (AMs). Rifampicin (RFP)-loaded solid lipid nanoparticles (RFP-SLNs) with an average size of 829.6 {+-} 16.1 nm were prepared by a modified lipid film hydration method. The cytotoxicity of RFP-SLNs to AMs and alveolar epithelial type II cells (AECs) was examined using MTT assays. The viability of AMs and AECs was above 80 % after treatment with RFP-SLNs, which showed low toxicity to both AMs and AECs. Confocal Laser Scanning Microscopy was employed to observe the interaction between RFP-SLNs and both AMs and AECs. After incubating the cells with RFP-SLNs for 2 h, the fluorescent intensity in AMs was more and remained longer (from 0.5 to 12 h) when compared with that in AECs (from 0.5 to 8 h). In vitro uptake characteristics of RFP-SLNs in AMs and AECs were also investigated by detection of intracellular RFP by High performance liquid chromatography. Results showed that RFP-SLNs delivered markedly higher RFP into AMs (691.7 ng/mg in cultured AMs, 662.6 ng/mg in primary AMs) than that into AECs (319.2 ng/mg in cultured AECs, 287.2 ng/mg in primary AECs). Subsequently, in vivo delivery efficiency and the selectivity of RFP-SLNs were further verified in Sprague-Dawley rats. Under pulmonary administration of RFP-SLNs, the amount of RFP in AMs was significantly higher than that in AECs at each time point. Our results demonstrated that solid lipid nanoparticles are a promising strategy for the delivery of rifampicin to alveolar macrophages selectively.

  6. Temperature dependent heterogeneous rotational correlation in lipids

    Science.gov (United States)

    Dadashvand, Neda; Othon, Christina M.

    2016-12-01

    Lipid structures exhibit complex and highly dynamic lateral structure; and changes in lipid density and fluidity are believed to play an essential role in membrane targeting and function. The dynamic structure of liquids on the molecular scale can exhibit complex transient density fluctuations. Here the lateral heterogeneity of lipid dynamics is explored in free standing lipid monolayers. As the temperature is lowered the probes exhibit increasingly broad and heterogeneous rotational correlation. This increase in heterogeneity appears to exhibit a critical onset, similar to those observed for glass forming fluids. We explore heterogeneous relaxation in in a single constituent lipid monolayer of 1, 2-dimyristoyl-sn-glycero-3-phosphocholine by measuring the rotational diffusion of a fluorescent probe (1-palmitoyl-2-[1]-sn-glycero-3-phosphocholine), which is embedded in the lipid monolayer at low labeling density. Dynamic distributions are measured using wide-field time-resolved fluorescence anisotropy. The observed relaxation exhibits a narrow, liquid-like distribution at high temperatures (τ ˜ 2.4 ns), consistent with previous experimental measures (Dadashvand et al 2014 Struct. Dyn. 1 054701, Loura and Ramalho 2007 Biochim. Biophys. Acta 1768 467-478). However, as the temperature is quenched, the distribution broadens, and we observe the appearance of a long relaxation population (τ ˜ 16.5 ns). This supports the heterogeneity observed for lipids at high packing densities, and demonstrates that the nanoscale diffusion and reorganization in lipid structures can be significantly complex, even in the simplest amorphous architectures. Dynamical heterogeneity of this form can have a significant impact on the organization, permeability and energetics of lipid membrane structures.

  7. LipidHome: a database of theoretical lipids optimized for high throughput mass spectrometry lipidomics.

    Directory of Open Access Journals (Sweden)

    Joseph M Foster

    Full Text Available Protein sequence databases are the pillar upon which modern proteomics is supported, representing a stable reference space of predicted and validated proteins. One example of such resources is UniProt, enriched with both expertly curated and automatic annotations. Taken largely for granted, similar mature resources such as UniProt are not available yet in some other "omics" fields, lipidomics being one of them. While having a seasoned community of wet lab scientists, lipidomics lies significantly behind proteomics in the adoption of data standards and other core bioinformatics concepts. This work aims to reduce the gap by developing an equivalent resource to UniProt called 'LipidHome', providing theoretically generated lipid molecules and useful metadata. Using the 'FASTLipid' Java library, a database was populated with theoretical lipids, generated from a set of community agreed upon chemical bounds. In parallel, a web application was developed to present the information and provide computational access via a web service. Designed specifically to accommodate high throughput mass spectrometry based approaches, lipids are organised into a hierarchy that reflects the variety in the structural resolution of lipid identifications. Additionally, cross-references to other lipid related resources and papers that cite specific lipids were used to annotate lipid records. The web application encompasses a browser for viewing lipid records and a 'tools' section where an MS1 search engine is currently implemented. LipidHome can be accessed at http://www.ebi.ac.uk/apweiler-srv/lipidhome.

  8. Lipid synthesis inhibitors: effect on epidermal lipid conformational changes and percutaneous permeation of levodopa.

    Science.gov (United States)

    Babita, Kumar; Rana, Vikas; Tiwary, Ashok K

    2005-10-24

    A combination of lipid synthesis inhibitors was used to enhance the in vitro and in vivo permeation of levodopa (LD) across rat epidermis, and their influence on epidermal lipids was investigated using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Rat epidermis was treated with ethanol and a combination of atorvastatin (750 microg/7 cm2), cerulenin (20 microg/7 cm2), and beta-chloroalanine (600 microg/7 cm2) for sustaining the reduced content of epidermal cholesterol, fatty acids (as triglycerides), and ceramide (as sphingosine), respectively, in viable rat skin. This treatment resulted in significant (P < .05) synthesis inhibition of skin lipids up to 48 hours and 6-fold enhancement in the in vitro permeation of LD. The effective plasma concentration of LD was achieved within 1 hour and maintained over 48 hours after topical application to rat epidermis treated with a combination of these lipid synthesis inhibitors. ATR-FTIR studies of inhibitor(s)-treated rat epidermis revealed a significant decrease (P < .05) in peak height and area for both asymmetric and symmetric C-H stretching absorbances, suggesting extraction of lipids. However, an insignificant (P < .05) shift in the frequency of these peaks suggested no fluidization of epidermal lipids by lipid synthesis inhibitors. A direct correlation was observed between epidermal lipid synthesis inhibition, decrease in peak height or area, and percutaneous permeation of LD. Skin lipid synthesis inhibition by a combination of lipid synthesis inhibitors seems to offer a feasible approach for enhancing the transcutaneous delivery of LD.

  9. The differential protein and lipid compositions of noncaveolar lipid microdomains and caveolae

    Institute of Scientific and Technical Information of China (English)

    Yao Yao; Shangyu Hong; Hu Zhou; Taichang Yuan; Rong Zeng; Kan Liao

    2009-01-01

    Morphologically, caveolae and lipid rafts are two different membrane structures. They are often reported to share similar lipid and protein compositions, and are considered to be two subtypes of membrane lipid microdomains. By modifying sucrose density gradient flotation centrifugation, which is used to isolate lipid microdomains, we were able to separate caveolae and noncaveolar lipid microdomains into two distinct fractions. The caveolar membranes are membrane vesicles of 100-nm diameter, enriched with caveolin-1 and flotillin-1. The noncaveolar lipid microdomains are amorphous membranes and most likely the coalescence of heterogeneous lipid rafts. They are depleted of caveolin-1 and are more enriched with cholesterol and sphingolipids than the caveolae. Many membrane proteins, such as insulin-like growth factor-1 receptor (membrane receptor), aquaporin-1 (membrane transporter), Thy-1 and N-cadherin (glycosylphosphatidylinositol-anchored membrane protein and membrane glycoprotein), are specifically associated with noncaveolar lipid microdomains, but not with caveolae. These results indicate that the lipid and protein compositions of caveolae differ from those of noncaveolar lipid microdomains. The difference in their protein compositions implies that these two membrane microdomains may have different cellular functions.

  10. DNA release from lipoplexes by anionic lipids: correlation with lipid mesomorphism, interfacial curvature, and membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Tarahovsky, Yury S.; Koynova, Rumiana; MacDonald, Robert C. (Northwestern)

    2010-01-18

    DNA release from lipoplexes is an essential step during lipofection and is probably a result of charge neutralization by cellular anionic lipids. As a model system to test this possibility, fluorescence resonance energy transfer between DNA and lipid covalently labeled with Cy3 and BODIPY, respectively, was used to monitor the release of DNA from lipid surfaces induced by anionic liposomes. The separation of DNA from lipid measured this way was considerably slower and less complete than that estimated with noncovalently labeled DNA, and depends on the lipid composition of both lipoplexes and anionic liposomes. This result was confirmed by centrifugal separation of released DNA and lipid. X-ray diffraction revealed a clear correlation of the DNA release capacity of the anionic lipids with the interfacial curvature of the mesomorphic structures developed when the anionic and cationic liposomes were mixed. DNA release also correlated with the rate of fusion of anionic liposomes with lipoplexes. It is concluded that the tendency to fuse and the phase preference of the mixed lipid membranes are key factors for the rate and extent of DNA release. The approach presented emphasizes the importance of the lipid composition of both lipoplexes and target membranes and suggests optimal transfection may be obtained by tailoring lipoplex composition to the lipid composition of target cells.

  11. An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER

    DEFF Research Database (Denmark)

    Markgraf, Daniel F; Klemm, Robin W; Junker, Mirco;

    2014-01-01

    Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary...... phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein (Ice2p) facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic...... and explain how cells switch neutral lipid metabolism from storage to consumption....

  12. Lipid - Motor Interactions: Soap Opera or Symphony?

    Science.gov (United States)

    Pathak, Divya; Mallik, Roop

    2017-02-01

    Intracellular transport of organelles can be driven by multiple motor proteins that bind to the lipid membrane of the organelle and work as a team. We review present knowledge on how lipids orchestrate the recruitment of motors to a membrane. Looking beyond recruitment, we also discuss how heterogeneity and local mechanical properties of the membrane may influence function of motor-teams. These issues gain importance because phagocytosed pathogens use lipid-centric strategies to manipulate motors and survive in host cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Lipides et comportement alimentaire chez les enfants

    Directory of Open Access Journals (Sweden)

    Nicklaus Sophie

    2016-05-01

    Full Text Available Cet article analyse la place des lipides dans l’alimentation des jeunes enfants. Premièrement, il montre d’une part la contribution importante que devraient avoir les lipides aux apports énergétiques totaux des enfants de moins de deux ans, en raison de leur intérêt fonctionnel dans le développement neuronal et de leur effet potentiellement protecteur d’une obésité ultérieure; d’autre part, il souligne la faible contribution des lipides aux apports énergétiques totaux chez les enfants français, d’après les estimations disponibles, avec une minorité d’enfants pour lesquels les apports en lipides sont satisfaisants. Deuxièmement, il rapporte les connaissances disponibles concernant le contrôle « sensoriel » de la consommation de lipides. Chez les nouveau-nés et les nourrissons, quelques travaux portent sur les préférences pour les lipides, et indiquent l’absence d’une préférence pour les lipides. Chez les enfants, une teneur augmentée en lipides a parfois (mais pas toujours un effet positif sur l’appréciation d’un aliment, avec souvent une teneur optimale; mais elle n’est pas associée à une consommation plus élevée de l’aliment. Des teneurs élevées en lipides ont deux effets sur les apprentissages alimentaires. Chez des enfants de moins de 3 ans, un triplement de la densité énergétique par l’ajout de lipides est associé à la mise en place d’un rassasiement conditionné pour l’aliment concerné; chez des enfants plus âgés, un doublement de la densité énergétique par l’ajout de lipides, est associé à une augmentation de l’appréciation des flaveurs associées aux versions les plus riches en lipides. Des pistes d’études complémentaires sont discutées.

  14. Binding of Serotonin to Lipid Membranes

    DEFF Research Database (Denmark)

    Peters, Günther H.J.; Wang, Chunhua; Cruys-Bagger, Nicolaj;

    2013-01-01

    dynamics (MD) simulations. 5-HT was found to interact strongly with lipid bilayers (partitioning coefficient ∼1200 in mole fraction units), and this is highly unusual for a hydrophilic solute like 5-HT which has a bulk, oil–water partitioning coefficient well below unity. It follows that membrane affinity...... and a prevailing residence between the phosphate and the carbonyl groups of the lipid. The unprotonated form of 5-HT shows the opposite orientation, with the primary amine pointing toward the membrane core. Partitioning of 5-HT was found to decrease lipid chain order. These distinctive interactions of 5-HT...

  15. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.

    1995-12-01

    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  16. LipidFrag: Improving reliability of in silico fragmentation of lipids and application to the Caenorhabditis elegans lipidome

    Science.gov (United States)

    Neumann, Steffen; Schmitt-Kopplin, Philippe

    2017-01-01

    Lipid identification is a major bottleneck in high-throughput lipidomics studies. However, tools for the analysis of lipid tandem MS spectra are rather limited. While the comparison against spectra in reference libraries is one of the preferred methods, these libraries are far from being complete. In order to improve identification rates, the in silico fragmentation tool MetFrag was combined with Lipid Maps and lipid-class specific classifiers which calculate probabilities for lipid class assignments. The resulting LipidFrag workflow was trained and evaluated on different commercially available lipid standard materials, measured with data dependent UPLC-Q-ToF-MS/MS acquisition. The automatic analysis was compared against manual MS/MS spectra interpretation. With the lipid class specific models, identification of the true positives was improved especially for cases where candidate lipids from different lipid classes had similar MetFrag scores by removing up to 56% of false positive results. This LipidFrag approach was then applied to MS/MS spectra of lipid extracts of the nematode Caenorhabditis elegans. Fragments explained by LipidFrag match known fragmentation pathways, e.g., neutral losses of lipid headgroups and fatty acid side chain fragments. Based on prediction models trained on standard lipid materials, high probabilities for correct annotations were achieved, which makes LipidFrag a good choice for automated lipid data analysis and reliability testing of lipid identifications. PMID:28278196

  17. Small Diameter Bomb Increment II (SDB II)

    Science.gov (United States)

    2013-12-01

    been further delays to the F-35 System Development and Demonstration ( SDD ) program. As a result, the SDB II integration will be accomplished as a...follow-on integration to the F-35 SDD . SDB II OT&E on the F-35 will not be completed by the FRP threshold of October 2019, thus delaying the FRP decision

  18. Microdomains Associated to Lipid Rafts.

    Science.gov (United States)

    Pacheco, Jonathan; Ramírez-Jarquín, Josué O; Vaca, Luis

    2016-01-01

    Store Operated Ca(2+) Entry (SOCE), the main Ca(2+) influx mechanism in non-excitable cells, is implicated in the immune response and has been reported to be affected in several pathologies including cancer. The basic molecular constituents of SOCE are Orai, the pore forming unit, and STIM, a multidomain protein with at least two principal functions: one is to sense the Ca(2+) content inside the lumen of the endoplasmic reticulum(ER) and the second is to activate Orai channels upon depletion of the ER. The link between Ca(2+) depletion inside the ER and Ca(2+) influx from extracellular media is through a direct association of STIM and Orai, but for this to occur, both molecules have to interact and form clusters where ER and plasma membrane (PM) are intimately apposed. In recent years a great number of components have been identified as participants in SOCE regulation, including regions of plasma membrane enriched in cholesterol and sphingolipids, the so called lipid rafts, which recruit a complex platform of specialized microdomains, which cells use to regulate spatiotemporal Ca(2+) signals.

  19. Oxidized lipoprotein lipids and atherosclerosis.

    Science.gov (United States)

    Ahotupa, Markku

    2017-04-01

    Plasma lipoproteins contain variable amounts of lipid oxidation products (LOP), which are known to impair normal physiological functions and stimulate atherosclerotic processes. Recent evidence indicates that plasma lipoproteins are active carriers of LOP, low-density lipoprotein (LDL) directing transport toward peripheral tissues, and high-density lipoprotein (HDL) being active in the reverse transport. It has been proposed that the lipoprotein-specific transport of LOP could play a role in atherosclerosis-related effects of LDL and HDL. This article gives an overview of the present knowledge of lipoprotein LOP transport and its association with the risk of atherosclerosis and cardiovascular diseases (CVD). Evidence of the significance of lipoprotein LOP transport comes mainly from studies of physiological oxidative stress and is supported by studies of the functionality apolipoprotein A-1 mimetic peptides. A large body of data has accumulated indicating that lipoprotein LOP transport is connected to the risk of atherosclerosis. While high levels of LOP carried by LDL are indicative of elevated risk, high LOP level in HDL appears to associate with protection. If confirmed, the proposed lipoprotein LOP transport function would affect conception of the etiology of atherosclerosis, but would not conflict current views of the pathophysiological mechanisms. It could open new perspectives, such as the dietary origin of LOP, and the protective function of HDL in clearance of LOP. Focusing on LOP could give additional tools especially for prevention and diagnosis, but would not radically change the management of atherosclerosis and CVD.

  20. Notch, lipids, and endothelial cells

    Science.gov (United States)

    Briot, Anaïs; Bouloumié, Anne; Iruela-Arispe, M. Luisa

    2017-01-01

    Purpose of review Notch signaling is an evolutionary conserved pathway critical for cardiovascular development and angiogenesis. More recently, the contribution of Notch signaling to the homeostasis of the adult vasculature has emerged as an important novel paradigm, but much remains to be understood. Recent findings Recent findings shed light on the impact of Notch in vascular and immune responses to microenvironmental signals as well as on the onset of atherosclerosis. In the past year, studies in human and mice explored the role of Notch in the maintenance of a nonactivated endothelium. Novel pieces of evidence suggest that this pathway is sensitive to environmental factors, including inflammatory mediators and diet-derived by-products. Summary An emerging theme is the ability of Notch to respond to changes in the microenvironment, including glucose and lipid metabolites. In turn, alterations in Notch enable an important link between metabolism and transcriptional changes, thus this receptor appears to function as a metabolic sensor with direct implications to gene expression. PMID:27454451

  1. Effects of losartan compared with atenolol on lipids in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension study

    DEFF Research Database (Denmark)

    Olsen, Michael Hecht; Wachtell, Kristian; Beevers, Gareth

    2009-01-01

    OBJECTIVE: Beta-blockers and angiotensin II receptor blockers have different effects on lipids. METHODS: We examined lipid levels in the Losartan Intervention For Endpoint reduction in hypertension study and their impact on the primary composite endpoint of cardiovascular death, myocardial...... or statin treatment. In Cox regression analysis, baseline total cholesterol [hazard ratio (HR) = 1.08 (1.02-1.14) per mmol/l, P

  2. Spastin binds to lipid droplets and affects lipid metabolism.

    Directory of Open Access Journals (Sweden)

    Chrisovalantis Papadopoulos

    2015-04-01

    Full Text Available Mutations in SPAST, encoding spastin, are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP. HSP is characterized by weakness and spasticity of the lower limbs, owing to progressive retrograde degeneration of the long corticospinal axons. Spastin is a conserved microtubule (MT-severing protein, involved in processes requiring rearrangement of the cytoskeleton in concert to membrane remodeling, such as neurite branching, axonal growth, midbody abscission, and endosome tubulation. Two isoforms of spastin are synthesized from alternative initiation codons (M1 and M87. We now show that spastin-M1 can sort from the endoplasmic reticulum (ER to pre- and mature lipid droplets (LDs. A hydrophobic motif comprised of amino acids 57 through 86 of spastin was sufficient to direct a reporter protein to LDs, while mutation of arginine 65 to glycine abolished LD targeting. Increased levels of spastin-M1 expression reduced the number but increased the size of LDs. Expression of a mutant unable to bind and sever MTs caused clustering of LDs. Consistent with these findings, ubiquitous overexpression of Dspastin in Drosophila led to bigger and less numerous LDs in the fat bodies and increased triacylglycerol levels. In contrast, Dspastin overexpression increased LD number when expressed specifically in skeletal muscles or nerves. Downregulation of Dspastin and expression of a dominant-negative variant decreased LD number in Drosophila nerves, skeletal muscle and fat bodies, and reduced triacylglycerol levels in the larvae. Moreover, we found reduced amount of fat stores in intestinal cells of worms in which the spas-1 homologue was either depleted by RNA interference or deleted. Taken together, our data uncovers an evolutionarily conserved role of spastin as a positive regulator of LD metabolism and open up the possibility that dysfunction of LDs in axons may contribute to the pathogenesis of HSP.

  3. [Effects of exogenous salicylic acid on membrane lipid peroxidation and photosynthetic characteristics of Cucumis sativus seedlings under drought stress].

    Science.gov (United States)

    Hao, Jing-Hong; Yi, Yang; Shang, Qing-Mao; Dong, Chun-Juan; Zhang, Zhi-Gang

    2012-03-01

    To approach the related mechanisms of exogenous salicylic acid (SA) in improving plant drought-resistance, this paper studied the effects of applying exogenous SA to the rhizosphere on the plant growth, membrane lipid peroxidation, proline accumulation, water use efficiency, net photosynthetic rate (Pn), and chlorophyll fluorescence parameters of cucumber (Cucumis sativus) seedlings under drought stresses (60% and 50% of saturated water capacity). Applying SA relieved the inhibitory effects of drought stress on plant growth, Pn, and water use efficiency, decreased membrane lipid peroxidation, and promoted proline accumulation. Meanwhile, the SA decreased the decrements of the maximum photochemical efficiency of PS II, actual photochemical efficiency of PS II, potential activity of PS II, effective photochemical efficiency of PS II, and photochemical quenching coefficient under drought stress significantly, and limited the increase of non-photochemical quenching coefficient. All the results suggested that applying exogenous SA could alleviate the oxidation damage of cell membrane resulted from the drought-caused membrane lipid peroxidation, improve the Pn by increasing PS II activity to benefit water utilization, enhance the regulation capability of osmosis to decrease water loss and increase water use efficiency, and thereby, improve the plant drought-resistance.

  4. Lipid partitioning in maize (Zea mays L.) endosperm highlights relationships among starch lipids, amylose, and vitreousness.

    Science.gov (United States)

    Gayral, Mathieu; Bakan, Bénédicte; Dalgalarrondo, Michele; Elmorjani, Khalil; Delluc, Caroline; Brunet, Sylvie; Linossier, Laurent; Morel, Marie-Hélène; Marion, Didier

    2015-04-08

    Content and composition of maize endosperm lipids and their partition in the floury and vitreous regions were determined for a set of inbred lines. Neutral lipids, i.e., triglycerides and free fatty acids, accounted for more than 80% of endosperm lipids and are almost 2 times higher in the floury than in the vitreous regions. The composition of endosperm lipids, including their fatty acid unsaturation levels, as well as their distribution may be related to metabolic specificities of the floury and vitreous regions in carbon and nitrogen storage and to the management of stress responses during endosperm cell development. Remarkably, the highest contents of starch lipids were observed systematically within the vitreous endosperm. These high amounts of starch lipids were mainly due to lysophosphatidylcholine and were tightly linked to the highest amylose content. Consequently, the formation of amylose-lysophosphatidylcholine complexes has to be considered as an outstanding mechanism affecting endosperm vitreousness.

  5. Investigation of Lipid Oxidation in High- and Low-Lipid-Containing Topical Skin Formulations

    DEFF Research Database (Denmark)

    Raagaard Thomsen, Birgitte; Frisenfeldt Horn, Anna; Hyldig, G.

    2017-01-01

    Abstract: Lipid oxidation can impact the odour of skin care products during storage. A study was conducted to identify and monitor representative markers for lipid oxidation in skin care products over time. Four lip care formulations and three skin care formulations with different lipid contents...... were stored at various cosmetic industry-relevant conditions for 84 days. The skin care products were analysed for lipid hydroperoxides and secondary volatile oxidation products. A trained sensory panel performed an odour difference (triangle) test and odour-profiled the products to detect and describe...... odour changes during storage. Several potential markers for lipid oxidation were identified. In skin care formulations, peroxide value (PV) analysis was a useful marker for lipid oxidation if the product was exposed to light during storage, but no clear changes were observed for PV in samples stored...

  6. Prolonged survival time of sarcoma 180-bearing mice treated with lipid microspheres-entrapped antitumor marine coral prostanoids.

    Science.gov (United States)

    Honda, A; Mori, Y; Yamada, Y; Nakaike, S; Hayashi, H; Otomo, S

    1988-09-01

    Antitumor marine coral prostanoids (clavulone II and chlorovulone I) were entrapped into lipid microspheres of 0.2 micron diameter to make lipo-drugs. Daily treatment with lipo-chlorovulone I (1.6 mg/kg/day, i.p.) and lipo-clavulone II (12.5 mg/kg/day, i.p.) on days 1 through 5 markedly prolonged the survival time (135% ILS and 73% ILS, respectively) of mice inoculated with sarcoma 180 as compared with that of a corresponding dose of respective free chlorovulone I and clavulone II. These results suggest that lipid microspheres may be used as drug delivery carriers for antitumor coral prostanoids in vivo.

  7. Computer Simulations of Lipid Bilayers and Proteins

    DEFF Research Database (Denmark)

    Sonne, Jacob

    2006-01-01

    , Pressure profile calculations in lipid bilayers: A lipid bilayer is merely $\\sim$5~nm thick, but the lateral pressure (parallel to the bilayer plane) varies several hundred bar on this short distance (normal to the bilayer). These variations in the lateral pressure are commonly referred to as the pressure...... of neglecting pressure contributions from long range electrostatic interactions. The first issue is addressed by comparing two methods for calculating pressure profiles, and judged by the similar results obtained by these two methods the pressure profile appears to be well-defined for fluid phase lipid bilayers......The importance of computer simulations in lipid bilayer research has become more prominent for the last couple of decades and as computers get even faster, simulations will play an increasingly important part of understanding the processes that take place in and across cell membranes. This thesis...

  8. Atomistic Monte Carlo simulation of lipid membranes

    DEFF Research Database (Denmark)

    Wüstner, Daniel; Sklenar, Heinz

    2014-01-01

    , as assessed by calculation of molecular energies and entropies. We also show transition from a crystalline-like to a fluid DPPC bilayer by the CBC local-move MC method, as indicated by the electron density profile, head group orientation, area per lipid, and whole-lipid displacements. We discuss the potential......Biological membranes are complex assemblies of many different molecules of which analysis demands a variety of experimental and computational approaches. In this article, we explain challenges and advantages of atomistic Monte Carlo (MC) simulation of lipid membranes. We provide an introduction...... into the various move sets that are implemented in current MC methods for efficient conformational sampling of lipids and other molecules. In the second part, we demonstrate for a concrete example, how an atomistic local-move set can be implemented for MC simulations of phospholipid monomers and bilayer patches...

  9. ER stress and hepatic lipid metabolism

    Directory of Open Access Journals (Sweden)

    Huiping eZhou

    2014-05-01

    Full Text Available The endoplasmic reticulum (ER is an important player in regulating protein synthesis and lipid metabolism. Perturbation of ER homeostasis, referred as ER stress, has been linked to numerous pathological conditions, such as inflammation, cardiovascular diseases and metabolic disorders. The liver plays a central role in regulating nutrient and lipid metabolism. Accumulating evidence implicates that ER stress disrupts lipid metabolism and induces hepatic lipotoxicity. Here, we review the major ER stress signaling pathways, how ER stress contributes to the dysregulation of hepatic lipid metabolism, and the potential causative mechanisms of ER stress in hepatic lipotoxicity. Understanding the role of ER stress in hepatic metabolism may lead to the identification of new therapeutic targets for metabolic diseases.

  10. Coalescence Kinetics of Lipid Based Bicelles

    Science.gov (United States)

    Hu, Andrew; Fan, Tai-Hsi; Katsaras, John; Xia, Yan; Li, Ming; Nieh, Mu-Ping

    2014-03-01

    Uniform nanodisc can be self-assembled from lipid mixtures of dimyristoyl phosphatidylcholine (DMPC), dimyristoyl phosphatidylglycerol (DMPG), and dihexanoyl phosphatidylcholine (DHPC). This study focuses on the theoretical and experimental growth kinetics of phospholipid based nanodiscs. Motivation for this project comes from the nanodisc's small size and their potential use as a carrier for drug delivery. It was observed that at high total lipid concentration the nanodiscs are stable at approximately 10 nm. However, growth of these nanodiscs is observed at relatively low total lipid concentrations. Dynamic light scattering (DLS) is used to monitor the size and growth rate of these nanodiscs at different solution conditions. The growth at low concentrations is caused by to the transfer of charged lipid (DMPG) from the discs to the solution, reducing the Columbic interaction. The growth of nanodisc as a function of size and surface potential is modeled using the Smoluchowski transport equation with transport-limited boundary conditions.

  11. A STUDY OF LIPID PROFILE IN PREDIABETES

    Directory of Open Access Journals (Sweden)

    Manoj

    2016-06-01

    Full Text Available BACKGROUND Lipid abnormalities are common in diabetes mellitus and play an important role in acceleration of atherosclerosis leading to increased cardiovascular diseases. Due to increasing burden of diabetes, it is becoming important to identify dyslipidaemia in high-risk state for diabetes especially prediabetes so that early intervention can reduce cardiovascular risk. AIM To study lipid profile in prediabetes individuals. METHODS This study was a cross-sectional case control study which included 107 prediabetes and 101 healthy controls. Lipid profile of prediabetes and controls were measured and statistically analysed. RESULT Total cholesterol, LDL, triglycerides, VLDL, TG/HDL ratio, and LDL/HDL ratio were significantly high whereas HDL was significantly low in prediabetes subjects as compared to controls. CONCLUSION This study showed significant lipid abnormalities in prediabetes subjects. Because of these they are at high risk of developing atherosclerotic cardiovascular diseases. Therefore, proper screening and appropriate therapy of these conditions becomes important.

  12. Voltage-gated lipid ion channels

    DEFF Research Database (Denmark)

    Blicher, Andreas; Heimburg, Thomas Rainer

    2013-01-01

    Synthetic lipid membranes can display channel-like ion conduction events even in the absence of proteins. We show here that these events are voltage-gated with a quadratic voltage dependence as expected from electrostatic theory of capacitors. To this end, we recorded channel traces and current...... histograms in patch-experiments on lipid membranes. We derived a theoretical current-voltage relationship for pores in lipid membranes that describes the experimental data very well when assuming an asymmetric membrane. We determined the equilibrium constant between closed and open state and the open...... probability as a function of voltage. The voltage-dependence of the lipid pores is found comparable to that of protein channels. Lifetime distributions of open and closed events indicate that the channel open distribution does not follow exponential statistics but rather power law behavior for long open times...

  13. Lipid measures and cardiovascular disease prediction

    NARCIS (Netherlands)

    van Wijk, D.F.; Stroes, E.S.G.; Kastelein, J.J.P.

    2009-01-01

    Traditional lipid measures are the cornerstone of risk assessment and treatment goals in cardiovascular prevention. Whereas the association between total, LDL-, HDL-cholesterol and cardiovascular disease risk has been generally acknowledged, the rather poor capacity to distinguish between patients

  14. Lipid profile, hyperglycaemia, systemic inflammation and ...

    African Journals Online (AJOL)

    Lipid profile, hyperglycaemia, systemic inflammation and anthropometry as ... Methods: A random sample of 233 children, aged 6-18 years, was used for ... test for equality of variances, one-way analysis of variance and Pearson correlations.

  15. Atomistic Monte Carlo simulation of lipid membranes

    DEFF Research Database (Denmark)

    Wüstner, Daniel; Sklenar, Heinz

    2014-01-01

    Biological membranes are complex assemblies of many different molecules of which analysis demands a variety of experimental and computational approaches. In this article, we explain challenges and advantages of atomistic Monte Carlo (MC) simulation of lipid membranes. We provide an introduction......, as assessed by calculation of molecular energies and entropies. We also show transition from a crystalline-like to a fluid DPPC bilayer by the CBC local-move MC method, as indicated by the electron density profile, head group orientation, area per lipid, and whole-lipid displacements. We discuss the potential...... of local-move MC methods in combination with molecular dynamics simulations, for example, for studying multi-component lipid membranes containing cholesterol....

  16. Lipid peroxidation in experimental uveitis: sequential studies.

    Science.gov (United States)

    Goto, H; Wu, G S; Chen, F; Kristeva, M; Sevanian, A; Rao, N A

    1992-06-01

    Previously we have detected the occurrence of retinal lipid peroxidation initiated by phagocyte-derived oxygen radicals in experimental autoimmune uveitis (EAU). In the current studies, the confirmation of inflammation-mediated lipid peroxidation was proceeded further to include measurement of multiple parameters, including conjugated dienes, ketodienes, thiobarbituric acid reactive substances and fluorescent chromolipids. The assay for myeloperoxidase, a measure for the number of polymorphonuclear leukocytes in the inflammatory sites was also carried out. The levels of all these parameters were followed through the course of EAU development. The sequential evaluation of histologic changes using both light and electron microscopy was also carried out and the results were correlated with lipid peroxidation indices. These data suggest that the retinal lipid peroxidation plays a causative role in the subsequent retinal degeneration.

  17. The impact of lipid composition on the stability of the tear fluid lipid layer

    DEFF Research Database (Denmark)

    Kulovesi, P.; Telenius, J.; Koivuniemi, A.

    2012-01-01

    The tear fluid protects the corneal epithelium from drying and pathogens and it also provides nutrients to these cells. Tear fluid is composed of an aqueous layer as well as a lipid layer that resides at the air-tear interface. The function of the lipid layer is to lower the surface tension of th......-neutral lipid ratio. The results provide a plausible rationale for the development of dry eye syndrome in blepharitis patients....

  18. Improved characterization of EV preparations based on protein to lipid ratio and lipid properties.

    Directory of Open Access Journals (Sweden)

    Xabier Osteikoetxea

    Full Text Available In recent years the study of extracellular vesicles has gathered much scientific and clinical interest. As the field is expanding, it is becoming clear that better methods for characterization and quantification of extracellular vesicles as well as better standards to compare studies are warranted. The goal of the present work was to find improved parameters to characterize extracellular vesicle preparations. Here we introduce a simple 96 well plate-based total lipid assay for determination of lipid content and protein to lipid ratios of extracellular vesicle preparations from various myeloid and lymphoid cell lines as well as blood plasma. These preparations included apoptotic bodies, microvesicles/microparticles, and exosomes isolated by size-based fractionation. We also investigated lipid bilayer order of extracellular vesicle subpopulations using Di-4-ANEPPDHQ lipid probe, and lipid composition using affinity reagents to clustered cholesterol (monoclonal anti-cholesterol antibody and ganglioside GM1 (cholera toxin subunit B. We have consistently found different protein to lipid ratios characteristic for the investigated extracellular vesicle subpopulations which were substantially altered in the case of vesicular damage or protein contamination. Spectral ratiometric imaging and flow cytometric analysis also revealed marked differences between the various vesicle populations in their lipid order and their clustered membrane cholesterol and GM1 content. Our study introduces for the first time a simple and readily available lipid assay to complement the widely used protein assays in order to better characterize extracellular vesicle preparations. Besides differentiating extracellular vesicle subpopulations, the novel parameters introduced in this work (protein to lipid ratio, lipid bilayer order, and lipid composition, may prove useful for quality control of extracellular vesicle related basic and clinical studies.

  19. Dietary sphingomyelin lowers hepatic lipid levels and inhibits intestinal cholesterol absorption in high-fat-fed mice.

    Directory of Open Access Journals (Sweden)

    Rosanna W S Chung

    Full Text Available Controlling intestinal lipid absorption is an important strategy for maintaining lipid homeostasis. Accumulation of lipids in the liver is a major risk factor for metabolic syndrome and nonalcoholic fatty liver disease. It is well-known that sphingomyelin (SM can inhibit intestinal cholesterol absorption. It is, however, unclear if dietary SM also lowers liver lipid levels. In the present study (i the effect of pure dietary egg SM on hepatic lipid metabolism and intestinal cholesterol absorption was measured with [(14C]cholesterol and [(3H]sitostanol in male C57BL/6 mice fed a high-fat (HF diet with or without 0.6% wt/wt SM for 18 days; and (ii hepatic lipid levels and gene expression were determined in mice given a HF diet with or without egg SM (0.3, 0.6 or 1.2% wt/wt for 4 weeks. Mice supplemented with SM (0.6% wt/wt had significantly increased fecal lipid and cholesterol output and reduced hepatic [(14C]cholesterol levels after 18 days. Relative to HF-fed mice, SM-supplemented HF-fed mice had significantly lower intestinal cholesterol absorption (-30%. Liver weight was significantly lower in the 1.2% wt/wt SM-supplemented mice (-18%. Total liver lipid (mg/organ was significantly reduced in the SM-supplemented mice (-33% and -40% in 0.6% wt/wt and 1.2% wt/wt SM, respectively, as were triglyceride and cholesterol levels. The reduction in liver triglycerides was due to inactivation of the LXR-SREBP-1c pathway. In conclusion, dietary egg SM has pronounced hepatic lipid-lowering properties in mice maintained on an obesogenic diet.

  20. Factor II deficiency

    Science.gov (United States)

    ... if one or more of these factors are missing or are not functioning like they should. Factor II is one such coagulation factor. Factor II deficiency runs in families (inherited) and is very rare. Both parents must ...

  1. Lipid Neuroprotectants and Traumatic Glaucomatous Neurodegeneration

    Science.gov (United States)

    2016-05-01

    uniquely present in the normal aqueous humor act as regulators of intraocular pressure . Methods, topical application of lipids, IOP measurements by...Intraocular pressure (IOP) has been measured in DBA/2J and normotensive monkeys (major goals 1 and 2). These results are presented in Figure 1 below...without pain or obvious symptoms. Specific lipids naturally present in the clear fluid of the anterior chamber of the eye in healthy individuals but

  2. Exogenous ether lipids predominantly target mitochondria

    DEFF Research Database (Denmark)

    Kuerschner, Lars; Richter, Doris; Hannibal-Bach, Hans Kristian

    2012-01-01

    Ether lipids are ubiquitous constituents of cellular membranes with no discrete cell biological function assigned yet. Using fluorescent polyene-ether lipids we analyzed their intracellular distribution in living cells by microscopy. Mitochondria and the endoplasmic reticulum accumulated high......, accumulated to mitochondria and induced morphological changes and cellular apoptosis. These data indicate that edelfosine could exert its pro-apoptotic power by targeting and damaging mitochondria and thereby inducing cellular apoptosis. In general, this study implies an important role of mitochondria...

  3. Lipid storage myopathies with unusual clinical manifestations

    Directory of Open Access Journals (Sweden)

    Uppin Megha

    2008-01-01

    Full Text Available We describe the clinical presentation, course and pathologic findings found in three adult patients with lipid storage myopathy. Excessive lipid storage was found in Type 1 fibers of muscle. Clinical improvement on oral levo-carnitine therapy suggests the possibility of carnitine deficiency as the most likely etiology in two of the patients and one had mitochondrial myopathy confirmed on genetic analysis.

  4. Exercise Intensity Modulation of Hepatic Lipid Metabolism

    OpenAIRE

    Lira, Fábio S.; Carnevali, Luiz C; Zanchi, Nelo E.; Ronaldo VT. Santos; Jean Marc Lavoie; Marília Seelaender

    2012-01-01

    Lipid metabolism in the liver is complex and involves the synthesis and secretion of very low density lipoproteins (VLDL), ketone bodies, and high rates of fatty acid oxidation, synthesis, and esterification. Exercise training induces several changes in lipid metabolism in the liver and affects VLDL secretion and fatty acid oxidation. These alterations are even more conspicuous in disease, as in obesity, and cancer cachexia. Our understanding of the mechanisms leading to metabolic adaptations...

  5. Lipid Microarray Biosensor for Biotoxin Detection.

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Anup K.; Throckmorton, Daniel J.; Moran-Mirabal, Jose C.; Edel, Joshua B.; Meyer, Grant D.; Craighead, Harold G.

    2006-05-01

    We present the use of micron-sized lipid domains, patterned onto planar substrates and within microfluidic channels, to assay the binding of bacterial toxins via total internal reflection fluorescence microscopy (TIRFM). The lipid domains were patterned using a polymer lift-off technique and consisted of ganglioside-populated DSPC:cholesterol supported lipid bilayers (SLBs). Lipid patterns were formed on the substrates by vesicle fusion followed by polymer lift-off, which revealed micron-sized SLBs containing either ganglioside GT1b or GM1. The ganglioside-populated SLB arrays were then exposed to either Cholera toxin subunit B (CTB) or Tetanus toxin fragment C (TTC). Binding was assayed on planar substrates by TIRFM down to 1 nM concentration for CTB and 100 nM for TTC. Apparent binding constants extracted from three different models applied to the binding curves suggest that binding of a protein to a lipid-based receptor is strongly affected by the lipid composition of the SLB and by the substrate on which the bilayer is formed. Patterning of SLBs inside microfluidic channels also allowed the preparation of lipid domains with different compositions on a single device. Arrays within microfluidic channels were used to achieve segregation and selective binding from a binary mixture of the toxin fragments in one device. The binding and segregation within the microfluidic channels was assayed with epifluorescence as proof of concept. We propose that the method used for patterning the lipid microarrays on planar substrates and within microfluidic channels can be easily adapted to proteins or nucleic acids and can be used for biosensor applications and cell stimulation assays under different flow conditions. KEYWORDS. Microarray, ganglioside, polymer lift-off, cholera toxin, tetanus toxin, TIRFM, binding constant.4

  6. Development and evaluation of lipid nanoparticles for camptothecin de-livery: a comparison of solid lipid nanoparticles, nanostructured lipid car-riers, and lipid emulsion

    Institute of Scientific and Technical Information of China (English)

    Zih-rou HUANG; Shu-chiou HUA; Yueh-lung YANG; Jia-you FANG

    2008-01-01

    Aim:Camptothecin is an anticancer drug that acta against a broad spectrum of tumors. The clinical application of camptothecin is limited by its insolubility, instability, and toxicity problems. The aim of this study was to develop and characterize lipid nanoparticles with different lipid cores which can circumvent these problems. Methods: Lipid nanoparticles made of Precirol (solid lipid nanoparticles; SLN-P), Compritol (SLN-C), Precirol+squalene (nanostructured lipid carriers; NLC), and squalene (a lipid emulsion; LE) as the lipid core ma-terial were prepared. These systems were assessed and compared by evaluat-ing the mean diameter, surface charge, molecular environment, camptothecin release, and cell viability against a melanoma. The safety and storage stability of these systems were also preliminarily examined. Results: The particle size ranged from 190 to 310 nm, with the NLC and LE showing the smallest and largest sizes, respectively. The in vitro drug release occurred in a sustained manner in decreasing order as follows: LE>NLC>SLN-P>SLN-C. It was found that varying the type of inner phase had profound effects on cell viability. The SLN-P generally showed higher cytotoxicity than the free control. The treat-ment of melanomas with the camptothecin-loaded SLN-C and NLC yielded cytotoxicity comparable to that of the free form. The percentage of erythrocyte hemolysis by all nanoparticles was ≤5%, suggesting a good tolerance to lipid nanoparticles. Conclusion: The results collectively suggest that the SLN-P may have the potential to serve as a delivery system for parenteral camptothecin ad-ministration because of the sustained drug release, strong cytotoxicity, limited hemolysis, and good storage stability.

  7. Lipid Measures and Cardiovascular Disease Prediction

    OpenAIRE

    van Wijk, Diederik F.; Stroes, Erik S. G.; Kastelein, John J.P.

    2009-01-01

    Traditional lipid measures are the cornerstone of risk assessment and treatment goals in cardiovascular prevention. Whereas the association between total, LDL-, HDL-cholesterol and cardiovascular disease risk has been generally acknowledged, the rather poor capacity to distinguish between patients who will and those who will not develop cardiovascular disease has prompted the search for further refinement of these traditional measures. A thorough understanding of lipid metabolism is mandatory...

  8. Trypanosoma cruzi Infection and Host Lipid Metabolism

    OpenAIRE

    2014-01-01

    Trypanosoma cruzi is the causative agent of Chagas disease. Approximately 8 million people are thought to be affected worldwide. Several players in host lipid metabolism have been implicated in T. cruzi-host interactions in recent research, including macrophages, adipocytes, low density lipoprotein (LDL), low density lipoprotein receptor (LDLR), and high density lipoprotein (HDL). All of these factors are required to maintain host lipid homeostasis and are intricately connected via several me...

  9. Rapid modification of retroviruses using lipid conjugates

    Science.gov (United States)

    Mukherjee, Nimisha G.; Lyon, L. Andrew; LeDoux, Joseph M.

    2009-02-01

    Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.

  10. Ionic interaction of sulfatide with choline lipids.

    Science.gov (United States)

    Abramson, M B; Katzman, R

    1968-08-09

    Aqueous systems of sphingomyelin-sulfatide and lecithin-sulfatide were compared with aqueous systems of the individual lipids. The acid capacity of the mixed lipids increased, a result of the formation of an ionic bond between the sulfate of one molecule and the positive nitrogen of the other, making the phosphate available for direct titration. Cholesterol reduces this ionic interaction, probably because of the increased spacing of the ionized groups.

  11. Tuning molecular interactions in lipid-oligonucleotides assemblies via locked nucleic acid (LNA)-based lipids.

    Science.gov (United States)

    Patwa, Amit; Salgado, Gilmar; Dole, François; Navailles, Laurence; Barthélémy, Philippe

    2013-11-07

    Hybrid nucleotide-lipids containing locked nucleic acid (LNA) show enhanced hybridization properties with complementary single strand RNAs compared to DNA lipid analogues. The LNA adenosine lipid features unique binding properties with a high binding affinity for poly-uridine and the entropically driven formation of a stable complex (K(d) ≈ 43 nM). Enhanced hybridization properties of LNA-based lipids should be applicable for the development of oligonucleotide (ON) delivery systems or as small molecule binders to RNA for novel therapeutic strategies.

  12. Binary lipids-based nanostructured lipid carriers for improved oral bioavailability of silymarin.

    Science.gov (United States)

    Shangguan, Mingzhu; Lu, Yi; Qi, Jianping; Han, Jin; Tian, Zhiqiang; Xie, Yunchang; Hu, Fuqiang; Yuan, Hailong; Wu, Wei

    2014-02-01

    The main purpose of this study was to prepare binary lipids-based nanostructured lipid carriers to improve the oral bioavailability of silymarin, a poorly water-soluble liver protectant. Silymarin-loaded nanostructured lipid carriers were prepared by the method of high-pressure homogenization with glycerol distearates (Precirol ATO-5) and oleic acid as the solid and liquid lipids, respectively, and lecithin (Lipoid E 100) and Tween-80 as the emulsifiers. The silymarin-nanostructured lipid carrier prepared under optimum conditions was spherical in shape with mean particle size of ∼78.87 nm, entrapment efficiency of 87.55%, loading capacity of 8.32%, and zeta potential of -65.3 mV, respectively. In vitro release of silymarin-nanostructured lipid carriers was very limited even after 12 h, while in vitro lipolysis showed fast digestion of nanostructured lipid carriers within 1 h. Relative oral bioavailability of silymarin-nanostructured lipid carriers in Beagle dogs was 2.54- and 3.10-fold that of marketed Legalon® and silymarin solid dispersion pellets, respectively. It was concluded that nanostructured lipid carriers were potential drug delivery systems to improve the bioavailability of silymarin. Other than improved dissolution, alternative mechanisms such as facilitated absorption as well as lymphatic transport may contribute to bioavailability enhancement.

  13. Cholecystokinin Elevates Mouse Plasma Lipids

    Science.gov (United States)

    Zhou, Lichun; Yang, Hong; Lin, Xinghua; Okoro, Emmanuel U.; Guo, Zhongmao

    2012-01-01

    Cholecystokinin (CCK) is a peptide hormone that induces bile release into the intestinal lumen which in turn aids in fat digestion and absorption in the intestine. While excretion of bile acids and cholesterol into the feces eliminates cholesterol from the body, this report examined the effect of CCK on increasing plasma cholesterol and triglycerides in mice. Our data demonstrated that intravenous injection of [Thr28, Nle31]-CCK at a dose of 50 ng/kg significantly increased plasma triglyceride and cholesterol levels by 22 and 31%, respectively, in fasting low-density lipoprotein receptor knockout (LDLR−/−) mice. The same dose of [Thr28, Nle31]-CCK induced 6 and 13% increases in plasma triglyceride and cholesterol, respectively, in wild-type mice. However, these particular before and after CCK treatment values did not achieve statistical significance. Oral feeding of olive oil further elevated plasma triglycerides, but did not alter plasma cholesterol levels in CCK-treated mice. The increased plasma cholesterol in CCK-treated mice was distributed in very-low, low and high density lipoproteins (VLDL, LDL and HDL) with less of an increase in HDL. Correspondingly, the plasma apolipoprotein (apo) B48, B100, apoE and apoAI levels were significantly higher in the CCK-treated mice than in untreated control mice. Ligation of the bile duct, blocking CCK receptors with proglumide or inhibition of Niemann-Pick C1 Like 1 transporter with ezetimibe reduced the hypercholesterolemic effect of [Thr28, Nle31]-CCK in LDLR−/− mice. These findings suggest that CCK-increased plasma cholesterol and triglycerides as a result of the reabsorption of biliary lipids from the intestine. PMID:23300532

  14. Cholecystokinin elevates mouse plasma lipids.

    Directory of Open Access Journals (Sweden)

    Lichun Zhou

    Full Text Available Cholecystokinin (CCK is a peptide hormone that induces bile release into the intestinal lumen which in turn aids in fat digestion and absorption in the intestine. While excretion of bile acids and cholesterol into the feces eliminates cholesterol from the body, this report examined the effect of CCK on increasing plasma cholesterol and triglycerides in mice. Our data demonstrated that intravenous injection of [Thr28, Nle31]-CCK at a dose of 50 ng/kg significantly increased plasma triglyceride and cholesterol levels by 22 and 31%, respectively, in fasting low-density lipoprotein receptor knockout (LDLR(-/- mice. The same dose of [Thr28, Nle31]-CCK induced 6 and 13% increases in plasma triglyceride and cholesterol, respectively, in wild-type mice. However, these particular before and after CCK treatment values did not achieve statistical significance. Oral feeding of olive oil further elevated plasma triglycerides, but did not alter plasma cholesterol levels in CCK-treated mice. The increased plasma cholesterol in CCK-treated mice was distributed in very-low, low and high density lipoproteins (VLDL, LDL and HDL with less of an increase in HDL. Correspondingly, the plasma apolipoprotein (apo B48, B100, apoE and apoAI levels were significantly higher in the CCK-treated mice than in untreated control mice. Ligation of the bile duct, blocking CCK receptors with proglumide or inhibition of Niemann-Pick C1 Like 1 transporter with ezetimibe reduced the hypercholesterolemic effect of [Thr28, Nle31]-CCK in LDLR(-/- mice. These findings suggest that CCK-increased plasma cholesterol and triglycerides as a result of the reabsorption of biliary lipids from the intestine.

  15. Engineering Rhodosporidium toruloides for increased lipid production.

    Science.gov (United States)

    Zhang, Shuyan; Skerker, Jeffrey M; Rutter, Charles D; Maurer, Matthew J; Arkin, Adam P; Rao, Christopher V

    2016-05-01

    Oleaginous yeast are promising organisms for the production of lipid-based chemicals and fuels from simple sugars. In this work, we explored Rhodosporidium toruloides for the production of lipid-based products. This oleaginous yeast natively produces lipids at high titers and can grow on glucose and xylose. As a first step, we sequenced the genomes of two strains, IFO0880, and IFO0559, and generated draft assemblies and annotations. We then used this information to engineer two R. toruloides strains for increased lipid production by over-expressing the native acetyl-CoA carboxylase and diacylglycerol acyltransferase genes using Agrobacterium tumefaciens mediated transformation. Our best strain, derived from IFO0880, was able to produce 16.4 ± 1.1 g/L lipid from 70 g/L glucose and 9.5 ± 1.3 g/L lipid from 70 g/L xylose in shake-flask experiments. This work represents one of the first examples of metabolic engineering in R. toruloides and establishes this yeast as a new platform for production of fatty-acid derived products.

  16. Functional organization of the HIV lipid envelope

    Science.gov (United States)

    Huarte, Nerea; Carravilla, Pablo; Cruz, Antonio; Lorizate, Maier; Nieto-Garai, Jon A.; Kräusslich, Hans-Georg; Pérez-Gil, Jesús; Requejo-Isidro, Jose; Nieva, José L.

    2016-01-01

    The chemical composition of the human immunodeficiency virus type 1 (HIV-1) membrane is critical for fusion and entry into target cells, suggesting that preservation of a functional lipid bilayer organization may be required for efficient infection. HIV-1 acquires its envelope from the host cell plasma membrane at sites enriched in raft-type lipids. Furthermore, infectious particles display aminophospholipids on their surface, indicative of dissipation of the inter-leaflet lipid asymmetry metabolically generated at cellular membranes. By combining two-photon excited Laurdan fluorescence imaging and atomic force microscopy, we have obtained unprecedented insights into the phase state of membranes reconstituted from viral lipids (i.e., extracted from infectious HIV-1 particles), established the role played by the different specimens in the mixtures, and characterized the effects of membrane-active virucidal agents on membrane organization. In determining the molecular basis underlying lipid packing and lateral heterogeneity of the HIV-1 membrane, our results may help develop compounds with antiviral activity acting by perturbing the functional organization of the lipid envelope. PMID:27678107

  17. Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis

    Directory of Open Access Journals (Sweden)

    Arya Bagus Boedi Iswanto

    2017-04-01

    Full Text Available Abstract: The specialized plasma membrane microdomains known as lipid rafts are enriched by sterols and sphingolipids. Lipid rafts facilitate cellular signal transduction by controlling the assembly of signaling molecules and membrane protein trafficking. Another specialized compartment of plant cells, the plasmodesmata (PD, which regulates the symplasmic intercellular movement of certain molecules between adjacent cells, also contains a phospholipid bilayer membrane. The dynamic permeability of plasmodesmata (PDs is highly controlled by plasmodesmata callose (PDC, which is synthesized by callose synthases (CalS and degraded by β-1,3-glucanases (BGs. In recent studies, remarkable observations regarding the correlation between lipid raft formation and symplasmic intracellular trafficking have been reported, and the PDC has been suggested to be the regulator of the size exclusion limit of PDs. It has been suggested that the alteration of lipid raft substances impairs PDC homeostasis, subsequently affecting PD functions. In this review, we discuss the substantial role of membrane lipid rafts in PDC homeostasis and provide avenues for understanding the fundamental behavior of the lipid raft–processed PDC.

  18. Persistence of virus lipid signatures upon silicification

    Science.gov (United States)

    Kyle, J.; Jahnke, L. L.; Stedman, K. M.

    2011-12-01

    To date there is no known evidence of viruses within the rock record. Their small size and absence of a metabolism has led to the hypothesis that they lack unique biological signatures, and the potential to become preserved. Biosignature research relevant to early Earth has focused on prokaryotic communities; however, the most abundant member of modern ecosystems, viruses, have been ignored. In order to establish a baseline for research on virus biosignatures, we have initiated laboratory research on known lipid-containing viruses. PRD1 is a lipid-containing virus that infects and replicates in Salmonella typhimurium LT2. PRD1 is a 65 nm spherical virus with an internal lipid membrane, which is a few nanometers thick. When the PRD1 virus stock was mixed with a 400 ppm SiO2 (final concentration) solution and incubated for six months. Fourier Transform Infrared Spectroscopy and lipid analysis using gas chromatography revealed that the virus lipids were still detectable despite complete removal of dissolved silica. Free fatty acids were also detected. Titers of infectious PRD1 viruses after six months in the presence of silica decreased 40 times more than without silica. Though virus biosignature research is in its incipient stages, the data suggest that virus lipid signatures are preserved under laboratory conditions and may offer the potential for contribution to the organic geochemical record.

  19. Mechanical Properties of Nanoscopic Lipid Domains.

    Science.gov (United States)

    Nickels, Jonathan D; Cheng, Xiaolin; Mostofian, Barmak; Stanley, Christopher; Lindner, Benjamin; Heberle, Frederick A; Perticaroli, Stefania; Feygenson, Mikhail; Egami, Takeshi; Standaert, Robert F; Smith, Jeremy C; Myles, Dean A A; Ohl, Michael; Katsaras, John

    2015-12-23

    The lipid raft hypothesis presents insights into how the cell membrane organizes proteins and lipids to accomplish its many vital functions. Yet basic questions remain about the physical mechanisms that lead to the formation, stability, and size of lipid rafts. As a result, much interest has been generated in the study of systems that contain similar lateral heterogeneities, or domains. In the current work we present an experimental approach that is capable of isolating the bending moduli of lipid domains. This is accomplished using neutron scattering and its unique sensitivity to the isotopes of hydrogen. Combining contrast matching approaches with inelastic neutron scattering, we isolate the bending modulus of ∼13 nm diameter domains residing in 60 nm unilamellar vesicles, whose lipid composition mimics the mammalian plasma membrane outer leaflet. Importantly, the bending modulus of the nanoscopic domains differs from the modulus of the continuous phase surrounding them. From additional structural measurements and all-atom simulations, we also determine that nanoscopic domains are in-register across the bilayer leaflets. Taken together, these results inform a number of theoretical models of domain/raft formation and highlight the fact that mismatches in bending modulus must be accounted for when explaining the emergence of lateral heterogeneities in lipid systems and biological membranes.

  20. Influence of Tribulus terrestris extract on lipid profile and endothelial structure in developing atherosclerotic lesions in the aorta of rabbits on a high-cholesterol diet.

    Science.gov (United States)

    Tuncer, M Altug; Yaymaci, Bengi; Sati, Leyla; Cayli, Sevil; Acar, Goksemin; Altug, Tuncay; Demir, Ramazan

    2009-01-01

    The aim of this study was to investigate the pleotropic effects of an extract of a traditional herb, Tribulus terrestris (TT), on the lipid profile and vascular endothelium of the abdominal aorta in New Zealand rabbits fed a cholesterol-rich diet. Eighteen rabbits were randomly divided into three groups (n=6 for each). One experimental group (EG-I) was given a cholesterol-rich diet, a second experimental group (EG-II) was treated with TT following a cholesterol-rich diet, and a control group (CG) was fed a standard diet. Blood samples were collected on day 0 and then at weeks 4 and 12 to determine total serum cholesterol (TC), high density lipid-cholesterol (HDL-C), low density lipid-cholesterol (LDL-C) and triglyceride (TG) levels. Tissues were collected from the abdominal aorta for immunohistochemistry and transmission and scanning electron microscopy. In EG-II, the serum lipid profile was significantly lower than that of EG-I at week 12 with a reduction of TC: 65%; LDL-C: 66%; HDL-C: 64%; TG: 55%. Ultrastructural analysis revealed that endothelial damage was more prominent in EG-I compared to EG-II. The ruptured endothelial linings and damaged cellular surfaces increased in EG-I compared to EG-II. Our data indicate that dietary intake of TT can significantly lower serum lipid profiles, decrease endothelial cellular surface damage and rupture and may partially repair the endothelial dysfunction resulting from hyperlipidemia.

  1. Generic sorting of raft lipids into secretory vesicles in yeast

    DEFF Research Database (Denmark)

    Surma, Michal A; Klose, Christian; Klemm, Robin W;

    2011-01-01

    a complete lipid overview of the yeast late secretory pathway. We could show that vesicles captured with different baits carry the same cargo and have almost identical lipid compositions; being highly enriched in ergosterol and sphingolipids. This finding indicates that lipid raft sorting is a generic...... feature of vesicles carrying PM cargo and suggests a common lipid-based mechanism for their formation....

  2. The metabolic importance of unabsorbed dietary lipids in the colon

    NARCIS (Netherlands)

    Vonk, RJ; Kalivianakis, M; Minich, DM; Bijleveld, CMA; Verkade, HJ

    1997-01-01

    Digestion and absorption of lipids is a highly efficient process. From Western diets about 95% will be absorbed. This implies that together with lipids from endogenous sources 6-8 g of lipids will enter the colon daily. This input significantly increases during various lipid malabsorption syndromes.

  3. Fluorescopic evaluation of protein-lipid relations in cellular signalling.

    NARCIS (Netherlands)

    Pap, E.H.W.

    1994-01-01

    IntroductionCellular communication is partly mediated through the modulation of protein activity, structure and dynamics by lipids. In contrast to the biochemical aspects of lipid signalling, relatively little is known about the physical properties of the "signal" lipids (lipids involved in cellular

  4. 8.3.Protein,carbohydrate and lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920049 Clinical studies on the relationshipbetween serum lipids and lipid peroxidation.GUO Hong (郭虹),et al.Cardiovasc instit &Fuwai Hosp,CAMS,Beijing.Chin Cir J 1991; 6(5):373-375.This paper presented the relationship amongserum lipid fractions,lipid peroxides (LPO) and

  5. Reactive Oxygen Species, Lipid Peroxidation and Antioxidative Defense Mechanism

    Directory of Open Access Journals (Sweden)

    Hossam S. EL-BELTAGI

    2013-05-01

    Full Text Available Lipid peroxidation can be defined as the oxidative deterioration of lipids containing any number of carbon-carbon double bonds. Lipid peroxidation is a well-established mechanism of cellular injury in both plants and animals, and is used as an indicator of oxidative stress in cells and tissues. Lipid peroxides are unstable and decompose to form a complex series of compounds including reactive carbonyl compounds. The oxidation of linoleates and cholesterol is discussed in some detail. Analytical methods for studying lipid peroxidation were mentioned. Various kinds of antioxidants with different functions inhibit lipid peroxidation and the deleterious effects caused by the lipid peroxidation products.

  6. Pengaruh pemberian yogurt sinbiotik tepung pisang tanduk terhadap profil lipid tikus sindrom metabolik

    Directory of Open Access Journals (Sweden)

    Zana Fitriana Octavia

    2017-04-01

    Full Text Available Background: The metabolic syndrome, which is characterized by hyperglycemia, obesity, dyslipidemia, hypertension, prothrombic and proinflamatory state, is a risk factor for cardiovascular disease and diabetes mellitus. The synbiotic yogurt of tanduk banana (Musa paradisiaca fa. corniculata flour contains lactic acid bacteria, fructooligosaccarides, flavonoids, and vitamin C which all of them play role in improving the lipid profile. Objective: The aim of this study was to prove the effect of synbiotic yogurt of tanduk banana flour on lipid profile of metabolic syndrome rats. Method: This study was an true experimental with pre-post test  control group design. The subject of this study were 18 metabolic syndrome male Wistar rats divided into 3 groups,i.e control group (standart diet, intervention group I (standart diet and synbiotic yogurt of banana flour 0,009 ml/g weight/day, and intervention group II (standart diet and synbiotic yogurt of banana flour 0,018 ml/g weight/day. The intervention period was 2 weeks. Different test before and after intervention used paired t-test. The difference test between groups used One-Way ANOVA and Kruskal wallis. Results: The result showed that both of intervention group improved lipid profile significantly (p<0,05. The intervention group II showed more effective improvement of lipid profile significantly (p<0,05 than intervention group I. The intervention group II decreased triglycerides level 41,56%; total cholesterol level 41,39%; LDL-cholesterol level 57,5%; and increased HDL-cholesterol level 139,62%. Conclucion: The intervention of synbiotic yogurt of  tanduk banana flour can decrease triglyceride level, total cholesterol level, LDL-cholesterol level, and increase HDL-cholesterol level.

  7. Bilayer Deformation, Pores, and Micellation Induced by Oxidized Lipids.

    Science.gov (United States)

    Boonnoy, Phansiri; Jarerattanachat, Viwan; Karttunen, Mikko; Wong-Ekkabut, Jirasak

    2015-12-17

    The influence of different oxidized lipids on lipid bilayers was investigated with 16 individual 1 μs atomistic molecular dynamics (MD) simulations. Binary mixtures of lipid bilayers of 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphatidylcholine (PLPC) and its peroxide and aldehyde products were performed at different concentrations. In addition, an asymmetrical short chain lipid, 1-palmitoyl-2-decanoyl-sn-glycero-3-phosphatidylcholine (PDPC), was used to compare the effects of polar/apolar groups in the lipid tail on lipid bilayer. Although water defects occurred with both aldehyde and peroxide lipids, full pore formation was observed only for aldehyde lipids. At medium concentrations the pores were stable. At higher concentrations, however, the pores became unstable and micellation occurred. Data analysis shows that aldehyde lipids' propensity for pore formation is due to their shorter and highly mobile tail. The highly polar peroxide lipids are stabilized by strong hydrogen bonds with interfacial water.

  8. Targeting bacteria via iminoboronate chemistry of amine-presenting lipids.

    Science.gov (United States)

    Bandyopadhyay, Anupam; McCarthy, Kelly A; Kelly, Michael A; Gao, Jianmin

    2015-03-12

    Synthetic molecules that target specific lipids serve as powerful tools for understanding membrane biology and may also enable new applications in biotechnology and medicine. For example, selective recognition of bacterial lipids may give rise to novel antibiotics, as well as diagnostic methods for bacterial infection. Currently known lipid-binding molecules primarily rely on noncovalent interactions to achieve lipid selectivity. Here we show that targeted recognition of lipids can be realized by selectively modifying the lipid of interest via covalent bond formation. Specifically, we report an unnatural amino acid that preferentially labels amine-presenting lipids via iminoboronate formation under physiological conditions. By targeting phosphatidylethanolamine and lysylphosphatidylglycerol, the two lipids enriched on bacterial cell surfaces, the iminoboronate chemistry allows potent labelling of Gram-positive bacteria even in the presence of 10% serum, while bypassing mammalian cells and Gram-negative bacteria. The covalent strategy for lipid recognition should be extendable to other important membrane lipids.

  9. Studying lipid-protein interactions with electron paramagnetic resonance spectroscopy of spin-labeled lipids.

    Science.gov (United States)

    Páli, Tibor; Kóta, Zoltán

    2013-01-01

    Spin label electron paramagnetic resonance (EPR) of lipid-protein interactions reveals crucial features of the structure and assembly of integral membrane proteins. Spin label EPR spectroscopy is the technique of choice to characterize the protein-solvating lipid shell in its highly dynamic nature, because the EPR spectra of lipids that are spin labeled close to the terminal methyl end of their acyl chains display two spectral components, those corresponding to lipids directly contacting the protein and those corresponding to lipids in the bulk fluid bilayer regions of the membrane. In this chapter, typical spin label EPR procedures are presented that allow determination of the stoichiometry of interaction of spin-labeled lipids with the intra-membranous region of membrane proteins or polypeptides, as well as the association constant of the spin-labeled lipid with respect to the host lipid. The lipids giving rise to the so-called immobile spectral component in the EPR spectrum of such samples are identified as the motionally restricted first-shell lipids solvating membrane proteins in biomembranes. Stoichiometry and selectivity are directly related to the structure of the intra-membranous sections of membrane-associated proteins or polypeptides and can be used to study the state of assembly of such proteins in the membrane. Since these characteristics of lipid-protein interactions are discussed in detail in the literature [see Marsh (Eur Biophys J 39:513-525, 2010) for a most recent review], here we focus more on how to spin label model and biomembranes and how to measure and analyze the two-component EPR spectra of spin-labeled lipids in phospholipid bilayers that contain proteins or polypeptides. After a description of how to prepare spin-labeled model and native biological membranes, we present the reader with computational procedures for determining the molar fraction of motionally restricted lipids when both, one, or none of the pure isolated-mobile or

  10. Non-enzymatically derived minor lipids found in Escherichia coli lipid extracts.

    Science.gov (United States)

    Garrett, Teresa A; Raetz, Christian R H; Son, Jennifer D; Richardson, Travis D; Bartling, Craig; Guan, Ziqiang

    2011-11-01

    Electrospray ionization mass spectrometry is a powerful technique to analyze lipid extracts especially for the identification of new lipid metabolites. A hurdle to lipid identification is the presence of solvent contaminants that hinder the identification of low abundance species or covalently modify abundant lipid species. We have identified several non-enzymatically derived minor lipid species in lipid extracts of Escherichia coli; phosphatidylmethanol, ethyl and methyl carbamates of PE and N-succinyl PE were identified in lipid extracts of E. coli. Phosphatidylmethanol (PM) was identified by exact mass measurement and collision induced dissociation tandem mass spectrometry (MS/MS). Extraction in the presence of deuterated methanol leads to a 3 atomic mass unit shift in the [M-H](-) ions of PM indicating its formation during extraction. Ethyl and methyl carbamates of PE, also identified by exact mass measurement and MS/MS, are likely to be formed by phosgene, a breakdown product of chloroform. Addition of phosgene to extractions containing synthetic PE significantly increases the levels of PE-MC detected in the lipid extracts by ESI-MS. Extraction in the presence of methylene chloride significantly reduced the levels of these lipid species. N-succinyl PE is formed from reaction of succinyl-CoA with PE during extraction. Interestingly N-succinyl PE can be formed in an aqueous reaction mixture in the absence of added E. coli proteins. This work highlights the reactivity of the amine of PE and emphasizes that careful extraction controls are required to ensure that new minor lipid species identified using mass spectrometry are indeed endogenous lipid metabolites.

  11. Triglyceride blisters in lipid bilayers: implications for lipid droplet biogenesis and the mobile lipid signal in cancer cell membranes.

    Directory of Open Access Journals (Sweden)

    Himanshu Khandelia

    Full Text Available Triglycerides have a limited solubility, around 3%, in phosphatidylcholine lipid bilayers. Using millisecond-scale course grained molecular dynamics simulations, we show that the model lipid bilayer can accommodate a higher concentration of triolein (TO than earlier anticipated, by sequestering triolein molecules to the bilayer center in the form of a disordered, isotropic, mobile neutral lipid aggregate, at least 17 nm in diameter, which forms spontaneously, and remains stable on at least the microsecond time scale. The results give credence to the hotly debated existence of mobile neutral lipid aggregates of unknown function present in malignant cells, and to the early biogenesis of lipid droplets accommodated between the two leaflets of the endoplasmic reticulum membrane. The TO aggregates give the bilayer a blister-like appearance, and will hinder the formation of multi-lamellar phases in model, and possibly living membranes. The blisters will result in anomalous membrane probe partitioning, which should be accounted for in the interpretation of probe-related measurements.

  12. Lipid metabolism in experimental animals

    Directory of Open Access Journals (Sweden)

    Sánchez-Muñiz, Francisco J.

    1998-08-01

    Full Text Available Publications are scarce in the way in chich metabolic processes are affected by the ingestion of heated fats used to prepare food. Similarly studies measuring metabolic effects of the consumption on fried food are poorly known. The purpose of this presentation is to summarize information on frying fats and frying foods upon lipid metabolism in experimental animals. Food consumption is equivalent or even higher when oils or the fat content of frying foods are poorly alterated decreasing their acceptability when their alteration degree increase. After 4hr. experiment the digestibility and absorption coefficients of a single dosis of thermooxidized oils were significantly decreased in rats, however the digestive utilization of frying thermooxidized oils included in diets showed very little change in comparison with unused oils by feeding trials on rats. Feeding rats different frying fats induced a slight hypercholesterolemic effect being the magnitude of this effect related to the linoleic decrease in diet produced by frying. However HDL, the main rat-cholesterol carrier, also increased, thus the serum cholesterol/HDL-cholesterol ratio did not change. Results suggest that rats fed frying fats adapt their lipoprotein metabolism increasing the number of HDL particles. Deep fat frying deeply changed the fatty acid composition of foods, being possible to increase their n-9 or n-6 fatty acid and to decrease the saturated fatty acid contents by frying. When olive oil-and sunflower oil-fried sardines were used as the only protein and fat sources of rats-diets in order to prevent the dietary hypercholesterolemia it was provided that both fried-sardine diets showed a powerful check effect on the cholesterol raising effect induced by dietary cholesterol. The negative effect of feeding rats cholesterol plus bovine bile to induce hypercholesterolemia on some cell-damage markers such as lactate dehydrogenase, transaminases, alkaline phosphatase, was

  13. Archaeological bone lipids as palaeodietary markers.

    Science.gov (United States)

    Colonese, André C; Farrell, Thomas; Lucquin, Alexandre; Firth, Daniel; Charlton, Sophy; Robson, Harry K; Alexander, Michelle; Craig, Oliver E

    2015-04-15

    Stable isotope analysis of archaeological and fossil bone samples can provide important insights into past environments, ecologies and diets. Previous studies have focused on stable carbon and nitrogen isotopes in bone collagen, or carbon isotopes in bone mineral (bioapatite). Carbon isotope analysis of lipids from archaeological bone has received much less attention, partly due to the lack of suitable methodologies allowing sufficient recovery of compounds for structural and isotopic characterisation. Here we show that lipids can be easily and reliably recovered from archaeological bone using a modified protocol, and that these provide complementary dietary information to other bone components. Human and animal bones were obtained from a variety of archaeological contexts. Lipids were sequentially extracted using solvent extraction (dichloromethane/methanol), followed by acidified methanol extraction (methanol/H2SO4). The lipids were then analysed by gas chromatography/mass spectrometry (GC/MS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). Appreciable amounts of endogenous lipid were recovered from archaeological bone. Importantly, a comparison between compound-specific and bulk collagen isotopic data shows that archaeological bone lipids reflect dietary input and can be used to distinguish between marine and terrestrial consumers, as well as between C3 and C4 plant consumers. Furthermore, the presence of essential fatty acids directly incorporated from diet to bone may provide additional palaeodietary information. Our findings suggest that archaeological bone lipids are a hitherto untapped resource of dietary information that offer additional insights to those gained from other isotopic analyses of bone. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Small particle size lipid emulsions, satiety and energy intake in lean men.

    Science.gov (United States)

    Chan, Y K; Budgett, S C; MacGibbon, A K; Quek, S Y; Kindleysides, S; Poppitt, S D

    2017-02-01

    Lipid emulsions have been proposed to suppress hunger and food intake. Whilst there is no consensus on optimal structural properties or mechanism of action, small particle size (small-PS) stable emulsions may have greatest efficacy. Fabuless®, a commercial lipid emulsion reported in some studies to decrease energy intake (EI), is a small-PS, 'hard' fat emulsion comprising highly saturated palm oil base (PS, 82nm). To determine whether small-PS dairy lipid emulsions can enhance satiety, firstly, we investigated 2 'soft' fat dairy emulsions generated using dairy and soy emulsifying agents (PS, 114nm and 121nm) and a non-emulsified dairy control. Secondly, we investigated a small-PS palmolein based 'hard' fat emulsion (fractionated palm oil, PS, 104nm) and non-emulsified control. This was a 6 arm, randomized, cross-over study in 18 lean men, with test lipids delivered in a breakfast meal: (i) Fabuless® emulsion (FEM); (ii) dairy emulsion with dairy emulsifier (DEDE); (iii) dairy emulsion with soy lecithin emulsifier (DESE); (iv) dairy control (DCON); (v) palmolein emulsion with dairy emulsifier (PEDE); (vi) palmolein control (PCON). Participants rated postprandial appetite sensations using visual analogue scales (VAS), and ad libitum energy intake (EI) was measured at a lunch meal 3.5h later. Dairy lipid emulsions did not significantly alter satiety ratings or change EI relative to dairy control (DEDE, 4035kJ; DESE, 3904kJ; DCON, 3985kJ; P>0.05) nor did palm oil based emulsion relative to non-emulsified control (PEDE, 3902 kJ; PCON, 3973kJ; P>0.05). There was no evidence that small-PS dairy lipid emulsions or commercial Fabuless altered short-term appetite or food intake in lean adults. Copyright © 2016. Published by Elsevier Inc.

  15. Reprogramming neutral lipid metabolism in mouse dendritic leucocytes hosting live Leishmania amazonensis amastigotes.

    Directory of Open Access Journals (Sweden)

    Hervé Lecoeur

    Full Text Available BACKGROUND: After loading with live Leishmania (L amazonensis amastigotes, mouse myeloid dendritic leucocytes/DLs are known to undergo reprogramming of their immune functions. In the study reported here, we investigated whether the presence of live L. amazonensis amastigotes in mouse bone marrow-derived DLs is able to trigger re-programming of DL lipid, and particularly neutral lipid metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Affymetrix-based transcriptional profiles were determined in C57BL/6 and DBA/2 mouse bone marrow-derived DLs that had been sorted from cultures exposed or not to live L. amazonensis amastigotes. This showed that live amastigote-hosting DLs exhibited a coordinated increase in: (i long-chain fatty acids (LCFA and cholesterol uptake/transport, (ii LCFA and cholesterol (re-esterification to triacyl-sn-glycerol (TAG and cholesteryl esters (CE, respectively. As these neutral lipids are known to make up the lipid body (LB core, oleic acid was added to DL cultures and LB accumulation was compared in live amastigote-hosting versus amastigote-free DLs by epi-fluorescence and transmission electron microscopy. This showed that LBs were both significantly larger and more numerous in live amastigote-hosting mouse dendritic leucocytes. Moreover, many of the larger LB showed intimate contact with the membrane of the parasitophorous vacuoles hosting the live L. amazonensis amastigotes. CONCLUSIONS/SIGNIFICANCE: As leucocyte LBs are known to be more than simple neutral lipid repositories, we set about addressing two related questions. Could LBs provide lipids to live amastigotes hosted within the DL parasitophorous vacuole and also deliver? Could LBs impact either directly or indirectly on the persistence of L. amazonensis amastigotes in rodent skin?

  16. Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in mice.

    NARCIS (Netherlands)

    n den Hil, E.F. Hoek-va; Keijer, J.; Bunschoten, A.; Vervoort, J.J.; Stankova, B.; Bekkenkamp, M.; Herreman, L.; Venema, D.; Hollman, P.C.H.; Tvrzicka, E.; Rietjens, I.M.C.M.; Schothorst, E.M. van

    2013-01-01

    Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and (1)

  17. Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in mice

    NARCIS (Netherlands)

    Hoek-van den Hil, E.F.; Keijer, J.; Bunschoten, A.; Vervoort, Jacques; Stankova, B.; Bekkenkamp-Grovestein, M.; Herreman, L.; Venema, D.P.; Hollman, P.C.H.; Tvrzicka, E.; Rietjens, I.; Schothorst, van E.M.

    2013-01-01

    Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H

  18. Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in mice.

    NARCIS (Netherlands)

    n den Hil, E.F. Hoek-va; Keijer, J.; Bunschoten, A.; Vervoort, J.J.; Stankova, B.; Bekkenkamp, M.; Herreman, L.; Venema, D.; Hollman, P.C.H.; Tvrzicka, E.; Rietjens, I.M.C.M.; Schothorst, E.M. van

    2013-01-01

    Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and (1)

  19. Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy.

    Science.gov (United States)

    Jaffrès, Paul-Alain; Gajate, Consuelo; Bouchet, Ana Maria; Couthon-Gourvès, Hélène; Chantôme, Aurélie; Potier-Cartereau, Marie; Besson, Pierre; Bougnoux, Philippe; Mollinedo, Faustino; Vandier, Christophe

    2016-09-01

    Synthetic alkyl lipids, such as the ether lipids edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and ohmline (1-O-hexadecyl-2-O-methyl-rac-glycero-3-β-lactose), are forming a class of antitumor agents that target cell membranes to induce apoptosis and to decrease cell migration/invasion, leading to the inhibition of tumor and metastasis development. In this review, we present the structure-activity relationship of edelfosine and ohmline, and we point out differences and similarities between these two amphiphilic compounds. We also discuss the mechanisms of action of these synthetic alkyl ether lipids (involving, among other structures and molecules, membrane domains, Fas/CD95 death receptor signaling, and ion channels), and highlight a key role for lipid rafts in the underlying process. The reorganization of lipid raft membrane domains induced by these alkyl lipids affects the function of death receptors and ion channels, thus leading to apoptosis and/or inhibition of cancer cell migration. The possible therapeutic use of these alkyl lipids and the clinical perspectives for these lipids in prevention or/and treatment of tumor development and metastasis are also discussed.

  20. Interactions and Translational Dynamics of Phosphatidylinositol Bisphosphate (PIP2) Lipids in Asymmetric Lipid Bilayers.

    Science.gov (United States)

    Shi, Xiaojun; Kohram, Maryam; Zhuang, Xiaodong; Smith, Adam W

    2016-02-23

    Phosphatidylinositol phosphate (PIP) lipids are critical to many cell signaling pathways, in part by acting as molecular beacons that recruit peripheral membrane proteins to specific locations within the plasma membrane. Understanding the biophysics of PIP-protein interactions is critical to developing a chemically detailed model of cell communication. Resolving such interactions is challenging, even in model membrane systems, because of the difficulty in preparing PIP-containing membranes with high fluidity and integrity. Here we report on a simple, vesicle-based protocol for preparing asymmetric supported lipid bilayers in which fluorescent PIP lipid analogues are found only on the top leaflet of the supported membrane facing the bulk solution. With this asymmetric distribution of lipids between the leaflets, the fluorescent signal from the PIP lipid analogue reports directly on interactions between the peripheral molecules and the top leaflet of the membrane. Asymmetric PIP-containing bilayers are an ideal platform to investigate the interaction of PIP with peripheral membrane proteins using fluorescence-based imaging approaches. We demonstrate their usefulness here with a combined fluorescence correlation spectroscopy and single particle tracking study of the interaction between PIP2 lipids and a polycationic polymer, quaternized polyvinylpyridine (QPVP). With this approach we are able to quantify the microscopic features of the mobility coupling between PIP2 lipids and polybasic QPVP. With single particle tracking we observe individual PIP2 lipids switch from Brownian to intermittent motion as they become transiently trapped by QPVP.

  1. Cidea controls lipid droplet fusion and lipid storage in brown and white adipose tissue.

    Science.gov (United States)

    Wu, Lizhen; Zhou, Linkang; Chen, Cheng; Gong, Jingyi; Xu, Li; Ye, Jing; Li, De; Li, Peng

    2014-01-01

    Excess lipid storage in adipose tissue results in the development of obesity and other metabolic disorders including diabetes, fatty liver and cardiovascular diseases. The lipid droplet (LD) is an important subcellular organelle responsible for lipid storage. We previously observed that Fsp27, a member of the CIDE family proteins, is localized to LD-contact sites and promotes atypical LD fusion and growth. Cidea, a close homolog of Fsp27, is expressed at high levels in brown adipose tissue. However, the exact role of Cidea in promoting LD fusion and lipid storage in adipose tissue remains unknown. Here, we expressed Cidea in Fsp27-knockdown adipocytes and observed that Cidea has similar activity to Fsp27 in promoting lipid storage and LD fusion and growth. Next, we generated Cidea and Fsp27 double-deficient mice and observed that these animals had drastically reduced adipose tissue mass and a strong lean phenotype. In addition, Cidea/Fsp27 double-deficient mice had improved insulin sensitivity and were intolerant to cold. Furthermore, we observed that the brown and white adipose tissues of Cidea/Fsp27 double-deficient mice had significantly reduced lipid storage and contained smaller LDs compared to those of Cidea or Fsp27 single deficient mice. Overall, these data reveal an important role of Cidea in controlling lipid droplet fusion, lipid storage in brown and white adipose tissue, and the development of obesity.

  2. A lipid E-MAP identifies Ubx2 as a critical regulator of lipid saturation and lipid bilayer stress

    DEFF Research Database (Denmark)

    Surma, Michal A; Klose, Christian; Peng, Debby

    2013-01-01

    Biological membranes are complex, and the mechanisms underlying their homeostasis are incompletely understood. Here, we present a quantitative genetic interaction map (E-MAP) focused on various aspects of lipid biology, including lipid metabolism, sorting, and trafficking. This E-MAP contains ∼250......) desaturase Ole1p. Loss of Ubx2p affects the transcriptional control of OLE1, resulting in impaired FA desaturation and a severe shift toward more saturated membrane lipids. Both the induction of the unfolded protein response and aberrant nuclear membrane morphologies observed in cells lacking UBX2...... are suppressed by the supplementation of unsaturated FAs. Our results point toward the existence of dedicated bilayer stress responses for membrane homeostasis....

  3. Dry cured ham quality as related to lipid quality of raw material and lipid changes during processing: a review.

    OpenAIRE

    Gilles, Gandemer

    2009-01-01

    Lipids play a key role in sensory traits of dry cured hams. Both the quantity and the composition of lipids in raw material affect dry-cured hams quality. The lipid characteristics strongly depend on rearing systems developed in different area in Europe. During processing, lipids undergo lipolysis and oxidation. Phospholipids are the main substrates of both lipolysis and oxidation. Lipolysis forms free fatty acids rich in polyunsaturated fatty acids all along the process. Lipids are also subj...

  4. Direct visualization of lipid domains in human skin stratum corneum's lipid membranes

    DEFF Research Database (Denmark)

    Plasencia, I; Norlen, Lars; Bagatolli, Luis

    2007-01-01

    ; and iii), whether pH has a direct effect on the lipid matrix phase behavior. In this work the lateral structure of membranes composed of lipids extracted from human skin stratum corneum was studied in a broad temperature range (10 degrees C-90 degrees C) using different techniques such as differential......The main function of skin is to serve as a physical barrier between the body and the environment. This barrier capacity is in turn a function of the physical state and structural organization of the stratum corneum extracellular lipid matrix. This lipid matrix is essentially composed of very long...... scanning calorimetry, fluorescence spectroscopy, and two-photon excitation and laser scanning confocal fluorescence microscopy. Here we show that hydrated bilayers of human skin stratum corneum lipids express a giant sponge-like morphology with dimensions corresponding to the global three...

  5. Chain ordering of hybrid lipids can stabilize domains in saturated/hybrid/cholesterol lipid membranes

    Science.gov (United States)

    Yamamoto, T.; Brewster, R.; Safran, S. A.

    2010-07-01

    We use a liquid-crystal model to predict that hybrid lipids (lipids that have one saturated and one unsaturated tail) can stabilize line interfaces between domains in mixed membranes of saturated lipids, hybrid lipids, and cholesterol (SHC membranes). The model predicts the phase separation of SHC membranes with both parabolic and loop binodals depending on the cholesterol concentration, modeled via an effective pressure. In some cases, the hybrid lipids can reduce the line tension to zero in SHC membranes at temperatures that approach the critical temperature as the pressure is increased. The differences in the hybrid saturated tail conformational order in bulk and at the interface are responsible for the reduction of the line tension.

  6. Single-component solid lipid nanocarriers prepared with ultra-long chain amphiphilic lipids

    DEFF Research Database (Denmark)

    Wei, Wei; Lu, Xiaonan; Wang, Zegao

    2017-01-01

    HYPOTHESIS: Synthetic sugar alcohol mono-behenates with high melting points, surface activity and resistance to enzymatic lipolysis, are expected to form stable single-component solid lipid nanocarriers (SC-SLNs). The preparation methods and the polar head group of the molecules should affect...... the smallest mean size (∼100nm with PdI of 0.26). In addition, they displayed high entrapment efficiency of fenofibrate (95%) and long term drug release. Nanocarriers prepared by emulsification-diffusion method entrapped fenofibrate into lipid bilayers. In contrast, Nanocarriers prepared by melting......-probe sonication method had a micelle structure with fenofibrate incorporated into a lipid monolayer. This study provides an insight into the systematic development of novel amphiphilic lipids for solid lipid-based drug delivery system....

  7. Interaction of antimicrobial peptides with lipid membranes

    Energy Technology Data Exchange (ETDEWEB)

    Hanulova, Maria

    2008-12-15

    This study aims to investigate the difference in the interaction of antimicrobial peptides with two classes of zwitterionic peptides, phosphatidylethanolamines (PE) and phosphatidylcholines (PC). Further experiments were performed on model membranes prepared from specific bacterial lipids, lipopolysaccharides (LPS) isolated from Salmonella minnesota. The structure of the lipid-peptide aqueous dispersions was studied by small-and wide-angle X-ray diffraction during heating and cooling from 5 to 85 C. The lipids and peptides were mixed at lipid-to-peptide ratios 10-10000 (POPE and POPC) or 2-50 (LPS). All experiments were performed at synchrotron soft condensed matter beamline A2 in Hasylab at Desy in Hamburg, Germany. The phases were identified and the lattice parameters were calculated. Alamethicin and melittin interact in similar ways with the lipids. Pure POPC forms only lamellar phases. POPE forms lamellar phases at low temperatures that upon heating transform into a highly curved inverse hexagonal phase. Insertion of the peptide induced inverse bicontinuous cubic phases which are an ideal compromise between the curvature stress and the packing frustration. Melittin usually induced a mixture of two cubic phases, Im3m and Pn3m, with a ratio of lattice parameters close to 1.279, related to the underlying minimal surfaces. They formed during the lamellar to hexagonal phase transition and persisted during cooling till the onset of the gel phase. The phases formed at different lipid-to-peptide ratios had very similar lattice parameters. Epitaxial relationships existed between coexisting cubic phases and hexagonal or lamellar phases due to confinement of all phases to an onion vesicle, a vesicle with several layers consisting of different lipid phases. Alamethicin induced the same cubic phases, although their formation and lattice parameters were dependent on the peptide concentration. The cubic phases formed during heating from the lamellar phase and their onset

  8. Lipid Metabolic Disturbances in Severe Sepsis: Clinical Significance and New Methods of Correction

    Directory of Open Access Journals (Sweden)

    O. G. Malkova

    2009-01-01

    Full Text Available Objective: to reveal the basic regularities in the development of lipid metabolic disturbances in severe sepsis and to evaluate the efficiency of parenteral use of new balanced lipid emulsions in this cohort of patients. Subjects and methods. A prospective study was conducted in 88 patients with severe sepsis of different etiologies in the intensive care unit (ICI, Sverdlovsk Regional Clinical Hospital One. Among the lipid metabolic parameters, serum cholesterol, triglycerides (TG, high-density lipoproteins, low-density lipoproteins, and atherogenicity index were measured. Out of the systemic inflammatory markers and the additional criteria for sepsis severity, the serum levels of C-reactive protein, nitric oxide, lactate, D-dimers, the anti-inflammatory cytokine IL-4 and the proinflammatory cytokine IL-8 were determined. Serum was taken on days 1, 3, 5, and 7 after admission to the ICI. The quantitative attributes were comparatively analyzed by the statistical program «Statistica 6.0». Results. The severity assessed by the APACHE II scale, the degree of multiple organ failures (MOF evaluated by the SOFA scale, and lung lesion according to the MURREY scale were found to be closely related to the baseline serum TG levels in patients with severe sepsis. The findings suggest that patients with high TG levels have much higher resuscitative mortality rates. The clinical evaluation of the efficiency of the new method for correction of lipid metabolic disturbances in severe sepsis has indicated that the patients receiving balanced (omega-3 fatty acids-enriched fat emulsions as 20% Lipoplus solution had lower APACHE II scores within the first 7 days of intensive therapy and significantly more positive SOFA MOF changes. Specific changes were revealed in the presence of systemic inflammatory markers, such as C-reactive protein, IL-8, and IL-4, which confirms that balanced lipid emulsions are able to affect the system of pro- and anti

  9. Orphan enzymes in ether lipid metabolism.

    Science.gov (United States)

    Watschinger, Katrin; Werner, Ernst R

    2013-01-01

    Ether lipids are an emerging class of lipids which have so far not been investigated and understood in every detail. They have important roles as membrane components of e.g. lens, brain and testis, and as mediators such as platelet-activating factor. The metabolic enzymes for biosynthesis and degradation have been investigated to some extent. As most involved enzymes are integral membrane proteins they are tricky to handle in biochemical protocols. The sequence of some ether lipid metabolising enzymes has only recently been reported and other sequences still remain obscure. Defined enzymes without assigned sequence are known as orphan enzymes. One of these enzymes with uncharacterised sequence is plasmanylethanolamine desaturase, a key enzyme for the biosynthesis of one of the most abundant phospholipids in our body, the plasmalogens. This review aims to briefly summarise known functions of ether lipids, give an overview on their metabolism including the most prominent members, platelet-activating factor and the plasmalogens. A special focus is set on the description of orphan enzymes in ether lipid metabolism and on the successful strategies how four previous orphans have recently been assigned a sequence. Only one of these four was characterised by classical protein purification and sequencing, whereas the other three required alternative strategies such as bioinformatic candidate gene selection and recombinant expression or development of an inhibitor and multidimensional metabolic profiling.

  10. Atomistic Monte Carlo simulation of lipid membranes.

    Science.gov (United States)

    Wüstner, Daniel; Sklenar, Heinz

    2014-01-24

    Biological membranes are complex assemblies of many different molecules of which analysis demands a variety of experimental and computational approaches. In this article, we explain challenges and advantages of atomistic Monte Carlo (MC) simulation of lipid membranes. We provide an introduction into the various move sets that are implemented in current MC methods for efficient conformational sampling of lipids and other molecules. In the second part, we demonstrate for a concrete example, how an atomistic local-move set can be implemented for MC simulations of phospholipid monomers and bilayer patches. We use our recently devised chain breakage/closure (CBC) local move set in the bond-/torsion angle space with the constant-bond-length approximation (CBLA) for the phospholipid dipalmitoylphosphatidylcholine (DPPC). We demonstrate rapid conformational equilibration for a single DPPC molecule, as assessed by calculation of molecular energies and entropies. We also show transition from a crystalline-like to a fluid DPPC bilayer by the CBC local-move MC method, as indicated by the electron density profile, head group orientation, area per lipid, and whole-lipid displacements. We discuss the potential of local-move MC methods in combination with molecular dynamics simulations, for example, for studying multi-component lipid membranes containing cholesterol.

  11. Biotechnology Applications of Tethered Lipid Bilayer Membranes

    Directory of Open Access Journals (Sweden)

    Joshua A. Jackman

    2012-12-01

    Full Text Available The importance of cell membranes in biological systems has prompted the development of model membrane platforms that recapitulate fundamental aspects of membrane biology, especially the lipid bilayer environment. Tethered lipid bilayers represent one of the most promising classes of model membranes and are based on the immobilization of a planar lipid bilayer on a solid support that enables characterization by a wide range of surface-sensitive analytical techniques. Moreover, as the result of molecular engineering inspired by biology, tethered bilayers are increasingly able to mimic fundamental properties of natural cell membranes, including fluidity, electrical sealing and hosting transmembrane proteins. At the same time, new methods have been employed to improve the durability of tethered bilayers, with shelf-lives now reaching the order of weeks and months. Taken together, the capabilities of tethered lipid bilayers have opened the door to biotechnology applications in healthcare, environmental monitoring and energy storage. In this review, several examples of such applications are presented. Beyond the particulars of each example, the focus of this review is on the emerging design and characterization strategies that made these applications possible. By drawing connections between these strategies and promising research results, future opportunities for tethered lipid bilayers within the biotechnology field are discussed.

  12. Intravenous Lipids for Preterm Infants: A Review

    Directory of Open Access Journals (Sweden)

    Ghassan S. A. Salama

    2015-01-01

    Full Text Available Extremely low birth weight infants (ELBW are born at a time when the fetus is undergoing rapid intrauterine brain and body growth. Continuation of this growth in the first several weeks postnatally during the time these infants are on ventilator support and receiving critical care is often a challenge. These infants are usually highly stressed and at risk for catabolism. Parenteral nutrition is needed in these infants because most cannot meet the majority of their nutritional needs using the enteral route. Despite adoption of a more aggressive approach with amino acid infusions, there still appears to be a reluctance to use early intravenous lipids. This is based on several dogmas that suggest that lipid infusions may be associated with the development or exacerbation of lung disease, displace bilirubin from albumin, exacerbate sepsis, and cause CNS injury and thrombocytopena. Several recent reviews have focused on intravenous nutrition for premature neonate, but very little exists that provides a comprehensive review of intravenous lipid for very low birth and other critically ill neonates. Here, we would like to provide a brief basic overview, of lipid biochemistry and metabolism of lipids, especially as they pertain to the preterm infant, discuss the origin of some of the current clinical practices, and provide a review of the literature, that can be used as a basis for revising clinical care, and provide some clarity in this controversial area, where clinical care is often based more on tradition and dogma than science.

  13. Lipid binding proteins from parasitic platyhelminthes.

    Science.gov (United States)

    Alvite, Gabriela; Esteves, Adriana

    2012-01-01

    TWO MAIN FAMILIES OF LIPID BINDING PROTEINS HAVE BEEN IDENTIFIED IN PARASITIC PLATYHELMINTHES: hydrophobic ligand binding proteins (HLBPs) and fatty acid binding proteins (FABPs). Members of the former family of proteins are specific to the Cestoda class, while FABPs are conserved across a wide range of animal species. Because Platyhelminthes are unable to synthesize their own lipids, these lipid-binding proteins are important molecules in these organisms. HLBPs are a high molecular mass complex of proteins and lipids. They are composed of subunits of low molecular mass proteins and a wide array of lipid molecules ranging from CoA esters to cholesterol. These proteins are excretory-secretory molecules and are key serological tools for diagnosis of diseases caused by cestodes. FABPs are mainly intracellular proteins of low molecular weight. They are also vaccine candidates. Despite that the knowledge of their function is scarce, the differences in their molecular organization, ligand preferences, intra/extracellular localization, evolution, and phylogenetic distribution, suggest that platyhelminths HLBPs and FABPs should play different functions. FABPs might be involved in the removal of fatty acids from the inner surface of the cell membrane and in their subsequent targeting to specific cellular destinations. In contrast, HLBPs might be involved in fatty acid uptake from the host environment.

  14. Status of Lipid Profile in Pregnancy

    Directory of Open Access Journals (Sweden)

    Deepak Parchwani

    2011-02-01

    Full Text Available Pregnancy greatly increases demand for metabolic fuels that are needed for growth and development of the fetus and its support structures. The total gestation related energy cost has been estimated at approximately 83000 kcal. The major change in energy expenditure and in the accumulation of fat occurs at different times during pregnancy. In the current study a serial study of serum lipids was performed in a group of women throughout gestation and six weeks post partum while they were having their usual diet and unrestricted daily activity. The control group consisted of non pregnant healthy women of child bearing age. Data was analyzed by SPSS software. All lipid fractions underwent a gradual and persistent rise throughout pregnancy with the exception of HDL-C i.e. a progressive rise was observed in serum total cholesterol, serum triglyceride, serum VLDL and LDL-C as pregnancy advances, while serum HDL-C showed a biphasic pattern, as initial rise and then decline in later third of pregnancy. However, during early pregnancy the values of all lipid fractions do not differ significantly from those for normal non pregnant controls. No significant difference was observed in vegetarian and non-vegetarian group in any of the lipid fractions in different trimester of pregnancy—so diet had no significant influence on lipid synthesis during pregnancy. [National J of Med Res 2011; 1(1.000: 10-12

  15. Integral hair lipid in human hair follicle.

    Science.gov (United States)

    Lee, Won-Soo

    2011-12-01

    Integral hair lipid (IHL) is bound to the keratinized cell surface to make an environmentally resistant lipid envelope. It is mainly positioned on the hair cuticle and inner root sheath. IHL in the hair follicle may regard as hair barrier to be similar to the epidermal lipid layer functioning as skin barrier. Major constituents of IHL are fatty acid, phytosphingosine, ceramide in decreasing order. Minor constituents of IHL are cholesterol, cholesterol sulfate and cholesterol oleate. Cuticle or cortical cell surface in hair are abundant in fatty acids unlike the keratinized area of epidermis or sebaceous gland, and about 30-40% of such fatty acids are composed of 18-methyl-eicosanoic acid which is known to be bound to proteins by ester or thioester bond. Various factors including moisture, solvent, oxidative damage during bleaching or permanent waving affect IHL. Photochemical changes also can occur in IHL as well as in hair protein and hair pigment. Lipid metabolism is thought to play an essential role in lipid envelope of hair, but also involvement in hair development and function. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Lipid Binding Proteins from Parasitic Platyhelmithes

    Directory of Open Access Journals (Sweden)

    Gabriela eAlvite

    2012-09-01

    Full Text Available Two main families of lipid binding proteins have been identified in parasitic Platyhelminthes: hydrophobic ligand binding proteins (HLBPs and fatty acid binding proteins (FABPs. Members of the former family of proteins are specific to the Cestoda class, while FABPs are conserved across a wide range of animal species. Because Platyhelminthes are unable to synthesise their own lipids, these lipid-binding proteins are important molecules in these organisms.HLBPs are a high molecular mass complex of proteins and lipids. They are composed of subunits of low molecular mass proteins and a wide array of lipid molecules ranging from CoA esters to cholesterol. These proteins are excretory-secretory molecules and are key serological tools for diagnosis of diseases caused by cestodes. FABPs are mainly intracellular proteins of low molecular weight. They are also vaccine candidates.Despite that the knowledge of their function is scarce, the differences in their molecular organisation, ligand preferences, intra/extracellular localisation, evolution, and phylogenetic distribution, suggest that platyhelminths HLBPs and FABPs should play different functions. FABPs might be involved in the removal of fatty acids from the inner surface of the cell membrane and in their subsequent targeting to specific cellular destinations. In contrast, HLBPs might be involved in fatty acid uptake from the host environment.

  17. Lipid-based antifungal agents: current status.

    Science.gov (United States)

    Arikan, S; Rex, J H

    2001-03-01

    Immunocompromised patients are well known to be predisposed to developing invasive fungal infections. These infections are usually difficult to diagnose and more importantly, the resulting mortality rate is high. The limited number of antifungal agents available and their high rate of toxicity are the major factors complicating the issue. However, the development of lipid-based formulations of existing antifungal agents has opened a new era in antifungal therapy. The best examples are the lipid-based amphotericin B preparations, amphotericin B lipid complex (ABLC; Abelcet), amphotericin B colloidal dispersion (ABCD; Amphotec or Amphocil), and liposomal amphotericin B (AmBisome). These formulations have shown that antifungal activity is maintained while toxicity is reduced. This progress is followed by the incorporation of nystatin into liposomes. Liposomal nystatin formulation is under development and studies of it have provided encouraging data. Finally, lipid-based formulations of hamycin, miconazole, and ketoconazole have been developed but remain experimental. Advances in technology of liposomes and other lipid formulations have provided promising new tools for management of fungal infections.

  18. Atomistic Monte Carlo Simulation of Lipid Membranes

    Directory of Open Access Journals (Sweden)

    Daniel Wüstner

    2014-01-01

    Full Text Available Biological membranes are complex assemblies of many different molecules of which analysis demands a variety of experimental and computational approaches. In this article, we explain challenges and advantages of atomistic Monte Carlo (MC simulation of lipid membranes. We provide an introduction into the various move sets that are implemented in current MC methods for efficient conformational sampling of lipids and other molecules. In the second part, we demonstrate for a concrete example, how an atomistic local-move set can be implemented for MC simulations of phospholipid monomers and bilayer patches. We use our recently devised chain breakage/closure (CBC local move set in the bond-/torsion angle space with the constant-bond-length approximation (CBLA for the phospholipid dipalmitoylphosphatidylcholine (DPPC. We demonstrate rapid conformational equilibration for a single DPPC molecule, as assessed by calculation of molecular energies and entropies. We also show transition from a crystalline-like to a fluid DPPC bilayer by the CBC local-move MC method, as indicated by the electron density profile, head group orientation, area per lipid, and whole-lipid displacements. We discuss the potential of local-move MC methods in combination with molecular dynamics simulations, for example, for studying multi-component lipid membranes containing cholesterol.

  19. Telmisartan-induced PPARγ activity attenuates lipid accumulation in VSMCs via induction of autophagy.

    Science.gov (United States)

    Li, Bing-Hu; Liao, Shao-Qiong; Yin, Yan-Wei; Long, Chun-Yan; Guo, Lu; Cao, Xiao-Jie; Liu, Yun; Zhou, Yi; Gao, Chang-Yue; Zhang, Li-Li; Li, Jing-Cheng

    2015-01-01

    Foam cell formation is the hallmark of atherosclerosis. Both telmisartan and autophagy protect against the development of atherosclerosis. However, it has yet to be elucidated whether telmisartan prevents vascular smooth muscle cell (VSMC)-derived foam cell formation. Vascular smooth muscle cells isolated from the thoracic aorta of male C57BL/6J mice were used for this study. To induce foam cell formation, primary VSMCs were incubated in 80 μg/ml oxLDL for 24 h. LC3, beclin-1, PPARγ, AMPK, p-AMPK, mTOR and p-mTOR expression were determined via Western blot. Lipid accumulation was evaluated via oil red O staining and intracellular total cholesterol level measurement. Our study demonstrated that telmisartan dose-dependently increased the expression of beclin-1, the LC3II/LC3I ratio and the quantity of GFP-labeled autophagosomes, displaying a peak effect at 10 μM. In control siRNA-transfected VSMCs, telmisartan (10 μM) decreased lipid droplet accumulation and the total cholesterol level significantly. In contrast, in Atg7 siRNA-transfected VSMCs, telmisartan failed to attenuate lipid accumulation. In addition, telmisartan dose-dependently increased the expression of PPARγ and p-AMPK and decreased the expression of p-mTOR. GW9662 attenuated the telmisartan-induced increase in PPARγ expression, the LC3-II/LC3-I ratio and p-AMPK expression and the telmisartan-induced decrease in p-mTOR expression. Compound C restored mTOR activity and abolished the increase in the LC3-II/LC3-I ratio. Rapamycin significantly reduced p-mTOR expression and increased the LC3-II/LC3-I ratio. In conclusion, this study provides evidence that the chronic pharmacological activation of the PPARγ-mediated autophagy pathway using telmisartan may represent a promising therapeutic strategy for atherosclerosis.

  20. Serum Lipid Profiles, Lipid Ratios and Chronic Kidney Disease in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Liying Zhang

    2014-07-01

    Full Text Available Aim: To examine the association of serum lipids, lipid ratios with Chronic Kidney Disease (CKD in a Chinese population. Methods: Data were drawn from a cross-sectional survey in China. CKD was defined as estimated glomerular filtration rate (eGFR < 60 mL/min/1.73m2 or albuminuria-to-creatinine ratio (ACR > 30 mg/g. Multivariable logistic regressions and multivariate regression models were used. Serum lipids and lipid ratios included total cholesterol (TC, triglyceride (TG, low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol (HDL-C, TG/HDL-C ratio, TC/HDL-C ratio and LDL-C/HDL-C ratio. Results: In men, only logarithm-transformed (log TG was associated with CKD. The odds ratio (every SD increment was 1.39 (95% CI 1.03–1.87, P = 0.03. In women, none of the serum lipids and lipid ratios was associated with CKD. Using multivariate regression models, it was shown that log TG and log TG/HDL-C were negatively correlated with eGFR (P < 0.05 in men and LDL-C and log LDL-C/HDL-C ratio were correlated with ACR in men. In female subjects, serum TC, log TG, log TG/HDL-C and log TC/HDL-C were negatively correlated with eGFR (P < 0.05. All of serum lipid profiles and lipid related ratio were not correlated with ACR in women. Conclusion: Serum TG is the only suitable predictor for CKD in men. However, in women, none of serum lipids and lipid ratio can be used as a predictor for CKD. Log TG and log TG/HDL-C are negatively correlated with eGFR in both genders.

  1. Theoretical Study on the Photosensitizer Mechanism of Phenalenone in Aqueous and Lipid Media.

    Science.gov (United States)

    Espinoza, César; Trigos, Ángel; Medina, Manuel E

    2016-08-11

    The photosensitizer ability of phenalenone was studied in aqueous and lipid media through the single electron transfer reactions, employing the density functional theory. Although phenalenone is a well-known photosensitizer and is widely used as an (1)O2 reference sensitizer, little is known about the reaction mechanism involved. In this study we carried out a single electron transfer reaction between the basal, excited, oxidized and reduced state of phenalenone with oxygen molecules such as (3)O2 and O2(•-). In aqueous media the photosensitizer capacity of phenalenone was measured through both type I and type II mechanisms. In lipid media the photosensitizer ability of phenalenone was attributed to the type II mechanism. The results indicated that the photosensitizer ability of phenalenone shows a heavy reliance on the media where the reaction occurs whether this is an aqueous or lipid media. Finally, this study supports the idea about that electron transfer reactions can be used to study the photosensitizer ability of molecules.

  2. Enhancing anaerobic digestion performance of crude lipid in food waste by enzymatic pretreatment.

    Science.gov (United States)

    Meng, Ying; Luan, Fubo; Yuan, Hairong; Chen, Xue; Li, Xiujin

    2017-01-01

    Three lipases were applied to hydrolyze the floatable grease (FG) in the food waste for eliminating FG inhibition and enhancing digestion performance in anaerobic process. Lipase-I, Lipase-II, and Lipase-III obtained from different sources were used. Animal fat (AF) and vegetable oil (VO) are major crude lipids in Chinese food waste, therefore, applied as substrates for anaerobic digestion tests. The results showed that Lipase-I and Lipase-II were capable of obviously releasing long chain fatty acid in AF, VO, and FG when hydrolyzed in the conditions of 24h, 1000-1500μL and 40-50°C. Compared to the untreated controls, the biomethane production rate were increased by 80.8-157.7%, 26.9-53.8%, and 37.0-40.7% for AF, VO, and FG, respectively, and the digestion time was shortened by 10-40d. The finding suggests that pretreating lipids with appropriate lipase could be one of effective methods for enhancing anaerobic digestion of food waste rich in crude lipid. Copyright © 2016. Published by Elsevier Ltd.

  3. Lipids and lipoteichoic acid of autolysis-defective Streptococcus faecium strains.

    Science.gov (United States)

    Shungu, D L; Cornett, J B; Shockman, G D

    1980-06-01

    Two of four previously isolated autolysis-defective mutants of Streptococcus faecium (Streptococcus faecalis ATCC 9790) incorporated substantially more [14C]glycerol into lipids and lipoteichoic acid than did the parent strain. Consistent with increased accumulation of lipids and lipoteichoic acid, significantly higher levels of phosphorus were found in the corresponding fractions of the two mutant strains than in the wild type. Although the autolysis-defective mutant strains contained the same assortment of lipids as the wild type, the relative amount of [14C]glycerol incorporated into diphosphatidylglycerol increased, accompanied by a decreased fraction of phosphatidylglycerol. These results suggested that increased cellular content of two types of substances, acylated lipoteichoic acid and lipids (notably diphosphatidylglycerol), which previously had been shown to be potent inhibitors of the N-acetylmuramoylhydrolase of this species, contributed to the autolysis-defective phenotype of these mutants. Consistent with this interpretation are observations that (i) cerulenin inhibition of fatty acid synthesis increased the rates of benzylpenicillin-induced cellular lysis and that (ii) Triton X-100 or Zwittergent 3-14 treatment could reveal the presence of otherwise cryptic but substantial levels of the active form of the autolysin in cells of three of four mutants and of the proteinase-activable latent form in all four mutants.

  4. A laboratory experiment of intact polar lipid degradation in sandy sediments

    Directory of Open Access Journals (Sweden)

    J. Logemann

    2011-03-01

    Full Text Available Intact polar lipids (IPLs are considered biomarkers for living biomass. Their degradation in marine sediments, however, is poorly understood and complicates interpretation of their occurrence in geological samples. To investigate the turnover of IPLs, a degradation experiment with anoxic sandy sediments from the North Sea was conducted. Intact cells of two organisms that do not naturally occur in North Sea sediments were chosen as IPL sources: (i Saccharomyces cerevisiae, representative for ester-bound acyl lipids that also occur in Bacteria, and (ii the archaeon Haloferax volcanii, representative for ether-bound isoprenoid lipids. Surprisingly, IPLs with phosphoester-bound head groups showed approximately the same degradation rate as IPLs with glycosidic head groups. Furthermore, the results indicate a relatively fast degradation of S. cerevisiae IPLs with ester-bound moieties (analogs of bacterial membrane lipids and no significant degradation of archaeal IPLs with ether-bound moieties. Pore water and 16S rRNA-based DGGE analysis showed only a minor influence of the IPL source on microbial metabolism and community profiles. Due to our results, the IPL-based quantification of Archaea and Bacteria should be interpreted with caution.

  5. A laboratory experiment of intact polar lipid degradation in sandy sediments

    Directory of Open Access Journals (Sweden)

    J. Logemann

    2011-09-01

    Full Text Available Intact polar lipids (IPLs are considered biomarkers for living biomass. Their degradation in marine sediments, however, is poorly understood and complicates interpretation of their occurrence in geological samples. To investigate the turnover of IPLs, a degradation experiment with anoxic sandy sediments from the North Sea was conducted. Intact cells of two organisms that do not naturally occur in North Sea sediments were chosen as IPL sources: (i Saccharomyces cerevisiae, representative for ester-bound acyl lipids that also occur in Bacteria, and (ii the archaeon Haloferax volcanii, representative for ether-bound isoprenoid lipids. Surprisingly, IPLs with phosphoester-bound head groups showed approximately the same degradation rate as IPLs with glycosidic head groups. Furthermore, the results indicate a relatively fast degradation of S. cerevisiae IPLs with ester-bound moieties (analogs of bacterial membrane lipids and no significant degradation of archaeal IPLs with ether-bound moieties. Pore water and 16S rRNA-based DGGE analysis showed only a minor influence of the IPL source on microbial metabolism and community profiles. Due to our results, the IPL-based quantification of Archaea and Bacteria should be interpreted with caution.

  6. Sex-related differences in lipid peroxidation and photoprotection in Pistacia lentiscus.

    Science.gov (United States)

    Juvany, Marta; Müller, Maren; Pintó-Marijuan, Marta; Munné-Bosch, Sergi

    2014-03-01

    Sex-related differences in the response of dioecious plants to abiotic stress have been poorly studied to date. This work explored to what extent sex may affect plant stress responses in Pistacia lentiscus L. (Anacardiaceae), a tree well adapted to Mediterranean climatic conditions. It was hypothesized that a greater reproductive effort in females may increase oxidative stress in leaves, particularly when plants are exposed to abiotic stress. Measurements of oxidative stress markers throughout the year revealed increased lipid peroxidation in females, but only during the winter. Enhanced lipid peroxidation in females was associated with reduced photoprotection, as indicated by reduced tocopherol levels and nonphotochemical quenching (NPQ) of chlorophyll fluorescence. Enhanced lipid peroxidation in females was also observed at predawn, which was associated with increased lipoxygenase activity and reduced cytokinin levels. An analysis of the differences between reproductive (R) and nonreproductive (NR) shoots showed an enhanced photoprotective capacity in R shoots compared to NR shoots in females. This capacity was characterized by an increased NPQ and a better antioxidant protection (increased carotenoid and tocopherol levels per unit of chlorophyll) in R compared to NR shoots. It is concluded that (i) females exhibit higher lipid peroxidation in leaves than males, but only during the winter (when sex-related differences in reproductive effort are the highest), (ii) this is associated with a lower photoprotective capacity at midday, as well as enhanced lipoxygenase activity and reduced cytokinin levels at predawn, and (iii) photoprotection capacity is higher in R relative to NR shoots in females.

  7. Lipid Bilayer Composition Affects Transmembrane Protein Orientation and Function

    Directory of Open Access Journals (Sweden)

    Katie D. Hickey

    2011-01-01

    Full Text Available Sperm membranes change in structure and composition upon ejaculation to undergo capacitation, a molecular transformation which enables spermatozoa to undergo the acrosome reaction and be capable of fertilization. Changes to the membrane environment including lipid composition, specifically lipid microdomains, may be responsible for enabling capacitation. To study the effect of lipid environment on proteins, liposomes were created using lipids extracted from bull sperm membranes, with or without a protein (Na+ K+-ATPase or -amylase. Protein incorporation, function, and orientation were determined. Fluorescence resonance energy transfer (FRET confirmed protein inclusion in the lipid bilayer, and protein function was confirmed using a colourometric assay of phosphate production from ATP cleavage. In the native lipid liposomes, ATPase was oriented with the subunit facing the outer leaflet, while changing the lipid composition to 50% native lipids and 50% exogenous lipids significantly altered this orientation of Na+ K+-ATPase within the membranes.

  8. ER Stress and Lipid Metabolism in Adipocytes

    Directory of Open Access Journals (Sweden)

    Beth S. Zha

    2012-01-01

    Full Text Available The role of endoplasmic reticulum (ER stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, we discuss the current understanding of the potential role of ER stress in lipid metabolism in adipocytes. In addition, we touch upon the interaction of ER stress and autophagy as well as inflammation. Inhibition of ER stress has the potential of decreasing the pathology in adipose tissue that is seen with energy overbalance.

  9. Biosynthesis and function of plant lipids

    Energy Technology Data Exchange (ETDEWEB)

    Thomson, W.W.; Mudd, J.B.; Gibbs, M. (eds.)

    1983-01-01

    The Sixth Annual Symposium in Botany and Plant Physiology was held January 13-15, 1983, at the University of California, Riverside. This volume comprises the papers that were presented. Subjects discussed at the symposium covered a wide range in the field of plant lipids. Biosynthesis of lipids occupied an important fraction of the presentations at the symposium. Subjects included detailed studies of the enzymes of fatty acid synthesis, several discussions of the incorporation of fatty acids into glycerolipids and the further modification of the fatty acids, and the synthesis of glycerolipids and desaturation of fatty acids in both maturing oilseeds and chloroplasts. The physicochemical studies of glycerolipids and sterols in artificial membranes have led to distinct conclusions about their behaviour which must be relevant in the biological membrane. Results on the functional consequences of modifying the galactolipid composition in the chloroplast were an encouraging sign of progress in the attempts to relate membrane lipid composition to physiological function.

  10. Assessing the nature of lipid raft membranes

    DEFF Research Database (Denmark)

    Niemelä, Perttu S; Ollila, Samuli; Hyvönen, Marja T

    2007-01-01

    to intriguing lateral pressure profiles that are distinctly different from corresponding profiles in nonraft-like membranes. The results propose that the functioning of certain classes of membrane proteins is regulated by changes in the lateral pressure profile, which can be altered by a change in lipid content....... of highly ordered lateral domains rich in sphingomyelin and cholesterol (CHOL). These domains, called functional lipid rafts, have been suggested to take part in a variety of dynamic cellular processes such as membrane trafficking, signal transduction, and regulation of the activity of membrane proteins....... However, despite the proposed importance of these domains, their properties, and even the precise nature of the lipid phases, have remained open issues mainly because the associated short time and length scales have posed a major challenge to experiments. In this work, we employ extensive atom...

  11. Drug targeting using solid lipid nanoparticles.

    Science.gov (United States)

    Rostami, Elham; Kashanian, Soheila; Azandaryani, Abbas H; Faramarzi, Hossain; Dolatabadi, Jafar Ezzati Nazhad; Omidfar, Kobra

    2014-07-01

    The present review aims to show the features of solid lipid nanoparticles (SLNs) which are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery and research. Because of some unique features of SLNs such as their unique size dependent properties it offers possibility to develop new therapeutics. A common denominator of all these SLN-based platforms is to deliver drugs into specific tissues or cells in a pathological setting with minimal adverse effects on bystander cells. SLNs are capable to incorporate drugs into nanocarriers which lead to a new prototype in drug delivery which maybe used for drug targeting. Hence solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery and hence attracted wide attention of researchers. This review presents a broad treatment of targeted solid lipid nanoparticles discussing their types such as antibody SLN, magnetic SLN, pH sensitive SLN and cationic SLN.

  12. Bioactive lipids in kidney physiology and pathophysiology

    Directory of Open Access Journals (Sweden)

    Daria Sałata

    2014-01-01

    Full Text Available Lipids not only have structural functions, but also play an important role as signaling and regulatory molecules and participate in many cellular processes such as proliferation, differentiation, migration, and apoptosis. Bioactive lipids act both as extracellular mediators, which are associated with receptors on the surface of cells, and intracellular mediators triggering different signal pathways. They are present and active in physiological conditions, and are also involved in the pathogenesis of inflammation, asthma, cancer, diabetes, and hypertension. Bioactive lipids such as derivatives of arachidonic acid and sphingolipids have an important role in renal development, physiology and in many renal diseases. Some of them are potential indicators of kidney damage degree and/or function of the transplanted kidneys.

  13. Apolipoprotein gene involved in lipid metabolism

    Science.gov (United States)

    Rubin, Edward; Pennacchio, Len A.

    2007-07-03

    Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.

  14. Atomic force microscopy of model lipid membranes.

    Science.gov (United States)

    Morandat, Sandrine; Azouzi, Slim; Beauvais, Estelle; Mastouri, Amira; El Kirat, Karim

    2013-02-01

    Supported lipid bilayers (SLBs) are biomimetic model systems that are now widely used to address the biophysical and biochemical properties of biological membranes. Two main methods are usually employed to form SLBs: the transfer of two successive monolayers by Langmuir-Blodgett or Langmuir-Schaefer techniques, and the fusion of preformed lipid vesicles. The transfer of lipid films on flat solid substrates offers the possibility to apply a wide range of surface analytical techniques that are very sensitive. Among them, atomic force microscopy (AFM) has opened new opportunities for determining the nanoscale organization of SLBs under physiological conditions. In this review, we first focus on the different protocols generally employed to prepare SLBs. Then, we describe AFM studies on the nanoscale lateral organization and mechanical properties of SLBs. Lastly, we survey recent developments in the AFM monitoring of bilayer alteration, remodeling, or digestion, by incubation with exogenous agents such as drugs, proteins, peptides, and nanoparticles.

  15. Characteristics of lipids and their feeding value in swine diets.

    Science.gov (United States)

    Kerr, Brian J; Kellner, Trey A; Shurson, Gerald C

    2015-01-01

    In livestock diets, energy is one of the most expensive nutritional components of feed formulation. Because lipids are a concentrated energy source, inclusion of lipids are known to affect growth rate and feed efficiency, but are also known to affect diet palatability, feed dustiness, and pellet quality. In reviewing the literature, the majority of research studies conducted on the subject of lipids have focused mainly on the effects of feeding presumably high quality lipids on growth performance, digestion, and metabolism in young animals. There is, however, the wide array of composition and quality differences among lipid sources available to the animal industry making it essential to understand differences in lipid composition and quality factors affecting their digestion and metabolism more fully. In addition there is often confusion in lipid nomenclature, measuring lipid content and composition, and evaluating quality factors necessary to understand the true feeding value to animals. Lastly, advances in understanding lipid digestion, post-absorption metabolism, and physiological processes (e.g., cell division and differentiation, immune function and inflammation); and in metabolic oxidative stress in the animal and lipid peroxidation, necessitates a more compressive assessment of factors affecting the value of lipid supplementation to livestock diets. The following review provides insight into lipid classification, digestion and absorption, lipid peroxidation indices, lipid quality and nutritional value, and antioxidants in growing pigs.

  16. Assessing the nature of lipid raft membranes.

    Directory of Open Access Journals (Sweden)

    Perttu S Niemelä

    2007-02-01

    Full Text Available The paradigm of biological membranes has recently gone through a major update. Instead of being fluid and homogeneous, recent studies suggest that membranes are characterized by transient domains with varying fluidity. In particular, a number of experimental studies have revealed the existence of highly ordered lateral domains rich in sphingomyelin and cholesterol (CHOL. These domains, called functional lipid rafts, have been suggested to take part in a variety of dynamic cellular processes such as membrane trafficking, signal transduction, and regulation of the activity of membrane proteins. However, despite the proposed importance of these domains, their properties, and even the precise nature of the lipid phases, have remained open issues mainly because the associated short time and length scales have posed a major challenge to experiments. In this work, we employ extensive atom-scale simulations to elucidate the properties of ternary raft mixtures with CHOL, palmitoylsphingomyelin (PSM, and palmitoyloleoylphosphatidylcholine. We simulate two bilayers of 1,024 lipids for 100 ns in the liquid-ordered phase and one system of the same size in the liquid-disordered phase. The studies provide evidence that the presence of PSM and CHOL in raft-like membranes leads to strongly packed and rigid bilayers. We also find that the simulated raft bilayers are characterized by nanoscale lateral heterogeneity, though the slow lateral diffusion renders the interpretation of the observed lateral heterogeneity more difficult. The findings reveal aspects of the role of favored (specific lipid-lipid interactions within rafts and clarify the prominent role of CHOL in altering the properties of the membrane locally in its neighborhood. Also, we show that the presence of PSM and CHOL in rafts leads to intriguing lateral pressure profiles that are distinctly different from corresponding profiles in nonraft-like membranes. The results propose that the functioning of

  17. Quininium tetrachloridozinc(II

    Directory of Open Access Journals (Sweden)

    Li-Zhuang Chen

    2009-10-01

    Full Text Available The asymmetric unit of the title compound {systematic name: 2-[hydroxy(6-methoxyquinolin-1-ium-4-ylmethyl]-8-vinylquinuclidin-1-ium tetrachloridozinc(II}, (C20H26N2O2[ZnCl4], consists of a double protonated quininium cation and a tetrachloridozinc(II anion. The ZnII ion is in a slightly distorted tetrahedral coordination environment. The crystal structure is stabilized by intermolecular N—H...Cl and O—H...Cl hydrogen bonds.

  18. Hydrosol II Project; El Proyecto Hydrosol II

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Martinez, A.

    2008-07-01

    At present energy production is based on the combustion of fossil fuels and is the main cause of greenhouse gas emissions, which is to say it is the main cause of the climate change that is affecting the planet. On a worldwide scale, the use of solar concentration systems with systems capable of dissociating water is considered, from both an energy and an economic standpoint, as the most important long-term goal in the production of solar fuels to reduce the costs of hydrogen and to ensure practically zero carbon dioxide emissions. The Hydrosol II project has the largest pilot plant of its kind, and the Hydrosol II reactors will be capable of breaking up the water molecule on the basis of thermochemical cycles at moderate temperatures. The Hydrosol II project pilot plant is now a reality, located in the SSPS heliostats field of the Almeria Solar Platform. (Author)

  19. Treatment of cocaine overdose with lipid emulsion.

    Science.gov (United States)

    Jakkala-Saibaba, R; Morgan, P G; Morton, G L

    2011-12-01

    We describe the management and recovery of a 28-year-old man following a history of overdose by nasal inhalation of cocaine. The patient was presented in a comatose state suffering from seizures and marked cardiovascularly instability. Intravenous lipid emulsion was administered following initial resuscitation and tracheal intubation, as a means of treating persistent cardiac arrhythmias and profound hypotension. Following lipid emulsion therapy, the patient's life-threatening cardiovascular parameters rapidly improved and he recovered well without any side effects, thus being discharged within 2 days. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

  20. Lipid peroxidation in adrenal and testicular microsomes.

    OpenAIRE

    1981-01-01

    Studies were carried out to determine the actions of and interactions between ascorbate, NADPH, Fe2+, and Fe3+ on lipid peroxidation in adrenal and testicular microsomes. Ascorbate-induced malonaldehyde production was maximal in adrenal and testicular microsomes at an ascorbate concentration of 1 X 10(-4)M. Fe2+, at levels between 10(-6) and 10(-3)M, produced concentration-dependent increases in lipid peroxidation in adrenal and testicular microsomes; Fe2+ had a far greater effect than Fe3+ i...