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  • Reorganization of platelet membrane sphingomyelins by adenosine diphosphate and ticagrelor
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-09-14
    Fatemeh Haghighi, Vahideh Rabani, Jean-Paul Pais-De-Barros, Siamak Davani

    Platelets are major targets for the treatment of thrombo-embolic disorders. Their plasma membrane contains specialized microdomains enriched in sphingomyelins and free cholesterol including membrane receptors. P2Y12 receptors need to be situated in these domains to be able to conduct activation signaling by adenosine diphosphate (ADP). We studied the impact of ticagrelor, a P2Y12 antagonist, and ADP on the composition and distribution of sphingomyelins in detergent-resistant membrane (DRM) of platelet membranes.Platelets were obtained from healthy donors. DRMs of platelet membranes were isolated in 4 experimental groups: control; ADP, with platelets stimulated by 20 μM ADP and 5 mM CaCl2; ticagrelor, with platelets incubated by ticagrelor 4µM methanol dissolved; and ticagrelor + ADP, with incubation by ticagrelor followed by stimulation by ADP as above.After mass spectrometry analysis, we found 16 species of sphingomyelins in platelet membrane DRMs. We also found that treatment with ticagrelor and stimulation by ADP could induce changes in the composition, distribution and concentration of sphingomyelins in membranes of platelets. In all groups, the predominant species of sphingomyelins in platelet membrane was d18:1/16:0.Taken together, our results show that stimulation by ADP or inhibition by ticagrelor changed the level and composition of sphingomyelins in platelet membranes. These changes might be considered as reorganization or new recruitment of certain types of sphingomyelins through the membrane.

    更新日期:2018-09-15
  • Temperature triggering of kinetically trapped self-assemblies in citrem-phospholipid nanoparticles
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-09-14
    Rama Prajapati, Stefan Salentinig, Anan Yaghmur
    更新日期:2018-09-15
  • 更新日期:2018-09-15
  • Preparation and Characterization of Nanostructured Lipid Carriers as Drug Delivery System: Influence of Liquid Lipid Types on Loading and Cytotoxicity
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-09-13
    A. Saedi, K. Rostamizadeh, M. Parsa, N. Dalali, N. Ahmadi

    In this study, we aimed to investigate the influence of liquid lipid types on different features of NLC. Four variations of liquid lipids such as coconut oil, fish oil, black seed oil and linseed oil were used, while for all variations, cetyl palmitate was used as the solid lipid. Different NLC were characterized and compared in terms of particle size, zeta potential, polydispersity index (PDI), drug entrapment percentage and drug loading capacity. The results indicated that NLC containing black seed oil has the smallest size. Other features like PDI, zeta potential and entrapment efficiency were the same for all the liquid lipids. By close margins, the NLC containing black seed oil had the highest percent of drug release and antioxidant activity compared to the rest. Diffusion was the major mechanism of the drug release according to the drug release kinetic fitted by Higuchi’s model. Differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FT-IR) confirmed no strong interaction between NLC constituents. The particles showed spherical shape morphology under atomic force microscopy (AFM). According to the cell viability assay on MCF-7 cell line, the curcumin loaded NLC composed of linseed oil showed better cytotoxic activity compared to the free curcumin.

    更新日期:2018-09-14
  • A sensitive and improved throughput UPLC-MS/MS quantitation method of total cytochrome P450 mediated arachidonic acid metabolites that can separate regio-isomers and cis/trans-EETs from human plasma
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-09-07
    Maxwell Zeigler, Dale Whittington, Nona Sotoodehnia, Rozenn N. Lemaitre, Rheem A. Totah

    A method for the detection and quantification of hydroxyl and epoxy arachidonic acid (AA) metabolites in human plasma was developed using liquid-liquid extraction, phospholipid saponification followed by derivatization of the acid moiety and liquid chromatographic tandem mass spectrometric detection. Derivatization with a pyridinium analog allowed for detection in the positive ion mode, greatly improving sensitivity and the stability of the more labile AA metabolites. The entire method utilizes a 96-well plate format, increasing sample throughput, and was optimized to measure 5-, 8-, 9-, 11-, 12-, 15-, 19-, and 20- hydroxyeicosatetraenoic acid (HETE), 5,6-, 8,9-, 11,12-, and 14,15- dihydroxyeicosatrienoic acid (DHET), and the regio- and cis-/ trans- isomers of 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid (EET). The method was validated for its applicability over the FA concentration range found in human plasma. Using 100 µL aliquots of pooled human plasma, EET levels, particularly 5,6-EET, were observed to be higher than previously reported, with measured concentrations of 23.6 ng/ml for 5,6-EET, 5.6 ng/mL for 5,6-trans-EET, 8.0 ng/mL for 8,9-EET, 1.9 ng/mL for 8,9-trans-EET, 8.8 ng/mL for 11,12-EET, 3.4 ng/mL for 11,12-trans-EET, 10.7 ng/mL for 14,15-EET, and 1.7 ng/mL 14,15-trans- EET. This method is suitable for larger population studies to elucidate the complex interactions between the eicosanoids and various disease states and may be used for quantitation of a wide variety of fatty acids beyond eicosanoids from small volumes of human plasma.

    更新日期:2018-09-09
  • Sphingolipids and lipid rafts: Novel concepts and methods of analysis
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-09-05
    Erhard Bieberich

    About twenty years ago, the functional lipid raft model of the plasma membrane was published. It took into account decades of research showing that cellular membranes are not just homogenous mixtures of lipids and proteins. Lateral anisotropy leads to assembly of membrane domains with specific lipid and protein composition regulating vesicular traffic, cell polarity, and cell signaling pathways in a plethora of biological processes. However, what appeared to be a clearly defined entity of clustered raft lipids and proteins became increasingly fluid over the years, and many of the fundamental questions about biogenesis and structure of lipid rafts remained unanswered. Experimental obstacles in visualizing lipids and their interactions hampered progress in understanding just how big rafts are, where and when they are formed, and with which proteins raft lipids interact. In recent years, we have begun to answer some of these questions and sphingolipids may take center stage in re-defining the meaning and functional significance of lipid rafts. In addition to the archetypical cholesterol-sphingomyelin raft with liquid ordered (Lo) phase and the liquid-disordered (Ld) non-raft regions of cellular membranes, a third type of microdomains termed ceramide-rich platforms (CRPs) with gel-like structure has been identified. CRPs are “ceramide rafts” that may offer some fresh view on the membrane mesostructure and answer several critical questions for our understanding of lipid rafts.

    更新日期:2018-09-05
  • Protein probes to visualize sphingomyelin and ceramide phosphoethanolamine
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-09-05
    Françoise Hullin-Matsuda, Motohide Murate, Toshihide Kobayashi

    Sphingomyelin (SM) is a major sphingolipid in mammalian cells whereas its analog, ceramide phosphoethanolamine (CPE) is found in trace amounts in mammalian cells and in larger amounts in invertebrates such as insect cells like Drosophila melanogaster. To visualize endogenous SM or CPE, we need specific probes able to recognize the chemical structure of the lipid, rather than its physical property. A limited number of proteins is known to specifically and strongly bind SM or CPE. These proteins are either toxins produced by non-mammalian organisms, subunits or fragments of toxins or a protein that has similar structure to a toxin. These proteins labeled with small fluorophore (e.g Alexa Fluor) or conjugated to fluorescent proteins (e.g mCherry) or other types of markers (e.g 125I, maltose-binding protein) are used to detect SM or CPE. Here we summarize the characteristics of specific SM-binding proteins, lysenin and equinatoxin; CPE- and SM/cholesterol (Chol) binding aegerolysin proteins, pleurotolysin A2, ostreolysin and erylysin A and SM/Chol-binding protein, nakanori. Then we give examples of their applications including their limitations related not only to their lipid specificity and binding constants, but also to the lipid organization in the membrane.

    更新日期:2018-09-05
  • Capstan-like mechanism in hyaluronan-phospholipid systems
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-08-23
    P. Beldowski, N. Kruszewska, S. Yuvan, Z. Dendzik, T. Goudoulas, A. Gadomski

    Functionality of articular cartilage results from complex interactions between its molecular components. Among many biomolecules, two are of prime importance for lubrication: hyaluronic acid (HA) and phospholipids (PL). The purpose of this study is to discuss a mechanism of interaction between these two components and how their synergies contribute to nanobiolubrication of articular cartilage. Preliminary molecular dynamics simulations have been performed to investigate these interactions by adopting a capstan-like mechanism of action. By applying a constant pulling force to both ends of a HA molecule, wrapped around a PL micelle, we viewed the rotation of the PL micelle. The simulations were performed upon two physicochemical constraints: force- and solvent-dependency. The results show the efficiency of rotation from intermolecular bond creation and annihilation. We found a direct relation between the available surface of the micelle and the magnitude of the force, which varies significantly through the unwinding. The movement of the attached molecules are characterized by a slide-to-roll relation, which is affected by the viscosity of the surrounding medium. As a consequence, two solvents were studied for specific force conditions and the molecular dynamics simulation exhibited double the slide-to-roll coefficient for the viscous solvent as compared to its low-viscosity limit.

    更新日期:2018-08-23
  • Characterization of self-assembled hybrid siloxane-phosphocholine bilayers
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-08-09
    Mark B. Frampton, Michael H.L. Nguyen, Mitchell DiPasquale, Robert Dick, Drew Marquardt, Paul M. Zelisko
    更新日期:2018-08-10
  • Examining the effect of regioisomerism on the physico-chemical properties of lysophosphatidylethanolamine-containing liposomes using fluoro probes
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-08-03
    Yusuke Yamamoto, Takayuki Furukawa, Seiji Takeda, Hiroyuki Kashida, Hitoshi Chiba, Shu-Ping Hui

    Lysophospholipids (LysoPLs) receive steadily increasing attention in the area of lipid chemistry and biology. However, the physico-chemical properties of individual LysoPL regioisomers have not yet been investigated. Herein, we report the synthesis of fluoro analogues of lysophosphatidylethanolamines (LPEs) and examine the physico-chemical properties of the LPE regioisomers using chemically synthesized fluoro probes.

    更新日期:2018-08-03
  • 更新日期:2018-08-02
  • 更新日期:2018-08-01
  • Synthesis of dansyl labeled sphingosine kinase 1 inhibitor
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-07-22
    Eun-Young Park, Taeho Lee, Yoon Sin Oh, Joo-Youn Lee, Jitendra Shrestha, Seung Woo Hong, Yun Ji Jin, GeunHyung Jo, Sanghee Kim, Gil Tae Hwang, Dong-Sul Han, Dong Jae Baek

    PF-543 is a non-sphingosine analogue with inhibitory effect against SK1, based on a Ki of 4.3 nM and 130-fold selectivity for SK1 over SK2. Since the development of PF-543, animal studies demonstrated its valuable role in multiple sclerosis, myocardial infarction, and colorectal cancer. We synthesized labeled PF-543 for biochemical studies involving SK1. Overall, the 8-step synthetic route used 3,5-dimethylphenol as the starting material. A docking study of SK1 and SK1 inhibitory activity confirmed the structural similarity between the synthetic dansyl-PF-543 and PF-543. We also provide fluorescence spectra of dansyl-PF-543.

    更新日期:2018-07-23
  • Retinoblastoma membrane models and their interactions with porphyrin photosensitisers: An infrared microspectroscopy study
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-07-17
    Donia ESSAID, Ali TFAYLI, Philippe MAILLARD, Christophe SANDT, Véronique ROSILIO, Arlette BAILLET-GUFFROY, Athena KASSELOURI

    Fourier Transform Infrared (FTIR) microspectroscopy was used to highlight the interactions between two photosensitisers (PS) of different geometries, TPPmOH4 and a glycoconjugated analogous, TPPDegMan, and lipid bilayers modelling retinoblastoma cell membranes. Retinoblastoma is a rare disease occurring in young infants, for whom conservative treatments may present harmful side-effects. Photodynamic therapy (PDT) is expected to induce less side-effects, as the photosensitiser is only activated when the tumour is illuminated. Since efficiency of the treatment relies on photosensitiser penetration in cancer cells, bilayers with three lipid compositions - pure SOPC, SOPC/SOPE/SOPS/Chol (56:23:11:10) and SOPC/SOPE/SOPS/Chol/CL (42:32:9:8:6) – were used as plasma and mitochondria model membranes. FTIR spectra showed that the interaction of the PSs with the lipid bilayers impacted the lipid organization of the latter, causing significant spectral variations. Both studied photosensitisers inserted at the level of lipid hydrophobic chains, increasing chain fluidity and disorder. This was confirmed by surface pressure measurements. Photosensitisers - TPPmOH4 more than TPPDegMan - also interacted with the polar region of the bilayer, forming hydrogen bonds with phosphate groups that induced major shifts of phosphate absorption bands. This difference in PS interaction with moieties in the polar region was more pronounced with the models with complex lipid composition.

    更新日期:2018-07-18
  • Click Chemistry in Sphingolipid Research
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-07-17
    Eduardo Izquierdo, Antonio Delgado

    The term “click chemistry” was firstly coined by K. B. Sharpless in 2001 to refer to reactions that are high yielding, wide in scope, produce only easily removable byproducts and are stereospecific and simple to perform. Since then, this concept has been further developed and a large number of chemical reactions that fulfil totally or partially these criteria have been identified, contributing to widen the structural diversity in drug discovery campaigns, and providing chemical biologists with invaluable tools for the development of bioorthogonal reactions. In this context, several examples of the application of this concept in glycobiology and in the study of protein-protein, protein-nucleic acid and even protein-lipid interactions can be found. However, far fewer protocols have been described for the interrogation of cellular processes related to sphingolipid functions and metabolism. This review seeks to provide a concise overview of the most recent additions of click chemistry strategies to the current chemical biology toolbox, including the use of sphingolipid probes suitably functionalized for in situ click reactions, and the preparation of novel sphingolipid analogues whose design has been driven by the versatility of the archetypal [3 + 2] azide-alkyne cycloaddition.

    更新日期:2018-07-18
  • Evidence of lipid rafts based on the partition and dynamic behavior of sphingomyelins
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-07-10
    Masanao Kinoshita, Kenichi G.N. Suzuki, Michio Murata, Nobuaki Matsumori

    Sphingomyelin (SM)-rich membrane nano-domains, called lipid rafts, have attracted the interest of researchers due to their potential involvement in the formation of signaling platform. Although there are many studies on lipid rafts, the direct observation of lipid rafts is still challenging owing to two critical reasons. One is the lack of an appropriate fluorescent probe mimicking the native behavior of raft lipids; fluorescent labeling often alters the intrinsic disposition of raft lipids. The other is their spatio-temporal stability; the size of lipid rafts is much smaller than the optical resolution of usual microscopy and their lifetime is much shorter than image acquisition duration. These issues are hampering the visualization of lipid rafts. Our review highlights the recent advances in microscopic techniques to visualize the partition and dynamic behavior of SMs, disclosing the detailed structure of lipid rafts. Moreover, we will elucidate the importance of SM-SM interactions in the stabilization of signaling platforms as lipid rafts.

    更新日期:2018-07-12
  • Mixed surfactant (altering chain length and head group) aggregates as an effective carrier for tuberculosis drug
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-07-03
    Arun Kumar, Rekha, S.K. Kansal, A.O. Ibhadon, S.K. Mehta

    Surface properties and aggregation behaviour of cationic-cationic and cationic-non-ionic mixed surfactant systems viz. Dodecylethyldimethylammonium bromide (DDAB) with a series of double chain cationic surfactants (DiDDAB, DMDTAB, and DODAB) and non-ionic surfactants (Brij 96, Tyloxapol and Tween 80) were analysed using surface tension and transmission electron microscopy (TEM). The effect of chain length of cationic surfactant and hydrophilic-lypophilic balance (HLB) prominently observed in critical aggregation (cac) value. The aqueous solubility of anti-tuberculosis drug: rifampicin (RIF) was comparatively studied by UV-visible spectroscopy in presence of formulated micelles and vesicles. RIF was significantly solubilised in aqueous medium using all the formulated aggregates. RIF is very unstable in basic medium (above pH-7) and in oxidizing media. Therefore, stability at pH-13 as well as in strong oxidising environment was monitored using UV-visible spectroscopy. To trace the locus of the drug encapsulation in the micelles/vesicles, fluorescence spectroscopy and TEM studies were carried out. Both the techniques stemmed in complimentary results and confirmed that, RIF is majorly populated at polar medium in cationic-cationic vesicles and favour to reside at hydrophobic medium of the nonionic-cationic micelles.

    更新日期:2018-07-04
  • Structural changes in cellular membranes induced by ionic liquids: From model to bacterial membranes
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-06-23
    G. Bhattacharya, R.P. Giri, A. Dubey, S. Mitra, R. Priyadarshni, A. Gupta, M.K. Mukhopadhyay, S.K. Ghosh
    更新日期:2018-06-25
  • Impact of the ceramide subspecies on the nanostructure of stratum corneum lipids using neutron scattering and molecular dynamics simulations. Part I: Impact of CER[NS]
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-05-30
    Thomas Schmitt, Rakesh Gupta, Stefan Lange, Stefan Sonnenberger, Bodo Dobner, Thomas Hauß, Beena Rai, Reinhard H.H. Neubert
    更新日期:2018-05-31
  • On the Prediction of Critical Micelle Concentration for Sugar-Based Non-Ionic Surfactants
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-05-30
    Alireza Baghban, Jafar Sasanipour, Mohsen Sarafbidabad, Amin Piri, Razieh Razavi

    Micellization phenomenon occurs in natural and technical processes, necessitating the need to develop predictive models capable of predicting self-assembly behavior of surfactants. A least squares support vector machine (LSSVM) based quantitative structure property relationships (QSPR) model is developed in order to predict critical micelle concentration (CMC) for sugar-based surfactants. Model development is based on training and validating a predictive LSSVM strategy using a comprehensive data base consisting of 83 sugar-based surfactants. Model’s reliability and robustness has been evaluated using different visual and statistical parameters, revealing its great predictive capabilities. Results are also compared to previously reported best multi-linear regression (BMLR) based QSPR and group contribution based models, showing better performance of the proposed LSSVM-based QSPR model regarding lower RMSE value of 0.023 compared to the group contribution based and the best results from BMLR-based QSPR.

    更新日期:2018-05-31
  • STRUCTURE OF THE COMPLEX OF CYTOCHROME C WITH CARDIOLIPIN IN NON-POLAR ENVIRONMENT
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-05-29
    G.K. Vladimirov, A.S. Vikulina, D.V. Volodkin, Yu.A. Vladimirov
    更新日期:2018-05-30
  • Regulation of Endogenic Metabolites by Rosuvastatin in Hyperlipidemia Patients: An Integration of Metabolomics and Lipidomics
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-05-28
    Hyunbeom Lee, Jong Min Choi, Joo-Youn Cho, Tae-Eun Kim, Hwa Jeong Lee, Byung Hwa Jung

    Rosuvastatin is a statin used to treat metabolic syndrome conditions, such as hyperlipidemia. It is relatively safe; however, fatal rhabdomyolysis or skeletal myopathy can sometimes occur. Therefore, to investigate the overall effects of rosuvastatin, including lipid lowering and adverse effects, metabolic profiling was performed using metabolomics and lipidomics after rosuvastatin administration. Specifically, the metabolic profiles between healthy subjects and patients with hyperlipidemia were compared and the metabolic changes related to the mechanism of the drug effect were proposed. Healthy volunteers (n = 32) and hyperlipidemic patients (n = 14) were orally administered rosuvastatin (20 mg) once a day for 3-8 weeks, and plasma and urine were collected. Metabolomics and lipidomics were performed using UHPLC-LTQ/Orbitrap/MS/MS for non-targeted analysis and UHPLC-TQ-MS/MS for targeted analysis. Using non-targeted analysis, we successfully profiled and identified 73 and 87 metabolites in healthy subjects and hyperlipidemia subjects, respectively. Through targeted analysis, we have also quantified 188 metabolites, including amino acids, biogenic amines, glycerophospholipids, and sphingolipids. The levels of L-carnitine, diacylglycerol, and acylcarnitines significantly decreased after rosuvastatin administration regardless of the group. The overall levels of fatty acids (FA) and lysophosphatidylcholines (LysoPC) increased, while phosphatidylcholines (PC) decreased only in the patient group. β-Oxidation decreased overall, while the production of polyunsaturated FA increased only in the hyperlipidemic patients. Using metabolic profiling, we have evaluated the alterations in the biochemical pathways, which may aid in a more detailed understanding of the effect of rosuvastatin. Patient-specific metabolomic and lipidomic profiles may serve as valuable markers for the understanding of the adverse effects associated with statin treatment.

    更新日期:2018-05-29
  • 更新日期:2018-05-27
  • Topical treatments with acylceramide dispersions restored stratum corneum lipid lamellar structures in a reconstructed human epidermis model
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-05-23
    Akina Nakaune-Iijima, Akinori Sugishima, Gen Omura, Hiroyuki Kitaoka, Tomoko Tashiro, Shigeki Kageyama, Ichiro Hatta

    Long-periodicity phase (LPP) lamellar structures in intercellular lipid matrixes of the stratum corneum (SC) are considered important for maintenance of skin permeability barriers. Acylceramides are essential components of LPP structures, and their absence influences skin barriers under physiological and pathological conditions, such as atopic dermatitis and dry skin. Although topical applications of acylceramide have been shown to facilitate maintenance of the skin barrier, it is unknown whether topically applied acylceramides are incorporated into intercellular lipids to form LPP structures. Thus, we assessed the effects of topical treatments with monomodal acylceramides on the formation of LPP structures in a surfactant-insulted reconstructed human epidermis model using small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) analyses. In SAXS experiments, LPP structures give rise to a diffraction peak which indicates the presence of a structure with a 13 nm real space repeat distance. LPP patterns of intercellular lipid matrixes in the SC were disrupted’ by surfactant treatments and were recovered by topical acylceramide treatments. TEM images also showed specific repeating patterns of LPP structures, indicating that topical acylceramide treatments facilitate recovery of LPP structures in the SC. The present data show that the application of acylceramides might temporarily modify the lipid structure to resemble that of normal skin although the underlying cause of dry or diseased skin is not fully clarified.

    更新日期:2018-05-24
  • Sphingomyelin Ability to Act as Chiral Selector using Nanodisc Electrokinetic Chromatography
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-05-10
    William M. Penny, Christopher P. Palmer

    Understanding how stereochemistry affects interactions with cell membranes is important for effective drug development. Chirality has been shown to greatly effect pharmaceutical distribution and metabolism within the cell. However it has been thought that interactions with, and passive diffusion through, the membrane are not stereochemically selective. Various studies have produced conflicting results regarding whether interactions with lipid bilayers are or can be stereoselective. In the current work, stereoselective interactions between a pair of atropisomers, R-(+)/(S)-(−) 1,1′-Bi-2-naphthol, and sphingomyelin nanodisc bilayers, are demonstrated. This is accomplished using nanodisc electrokinetic chromatography, demonstrating that this approach is sensitive to subtle differences in affinity between small molecule probes and lipid bilayers. Using the same approach, no evidence of stereoselectivity was observed using enantiomer or diastereomer probes of varied chemistry and structure.

    更新日期:2018-05-17
  • How Cardiolipin Peroxidation Alters the Properties of the Inner Mitochondrial Membrane?
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-05-01
    Marjut Vähäheikkilä, Tapio Peltomaa, Tomasz Róg, Mario Vazdar, Sanja Pöyry, Ilpo Vattulainen

    Cardiolipins have multiple vital functions within biological cell membranes, most notably in the energy metabolism associated with the inner mitochondrial membrane. Considering their essential role, peroxidation of cardiolipins may plausibly have significant effects, as peroxidation is known to alter the functionality of lipid molecules. We used atomistic molecular dynamics simulations to study how peroxidation of cardiolipin affects the properties of the inner mitochondrial membrane. To this end, we explored what happens when varying fractions of fatty acid chains of cardiolipin are replaced by its four different oxidized products in systems modeling the inner mitochondrial membrane. We found that the oxidation of cardiolipin leads to a conformational change both in the backbone/head group and in chain regions of oxidized cardiolipin molecules. The oxidized groups were observed to shift closer to the membrane-water interface region, where they formed hydrogen bonds with several other groups. Additionally, the conformational change turned out to decrease bilayer thickness, and to increase the area per lipid chain, though these changes were minor. The acyl chain conformational order of unoxidized lipids exposed to interactions with oxidized cardiolipins was increased in carbons 3–5 and decreased in carbons 13–17 due to the structural reorganization of the cardiolipin molecules. Overall, the results bring up that the conformation of cardiolipin is altered upon oxidation, suggesting that its oxidation may interfere its interactions with mitochondrial proteins and thereby affect cardiolipin-dependent cellular processes such as electron and proton transport.

    更新日期:2018-05-01
  • Highly Effective Solvent Free Esterification of Phytosterols Employing Edible Metal Oxide-Emulsifier as Catalyst
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-05-01
    Huina Ruan, Lujing Xu, Shan Hong, Songbai Liu

    A general highly efficient solvent-free esterification of phytosterols with edible magnesium oxide and Span-60 emulsifier catalyst system has been developed. The edible emulsifier dramatically promotes the catalyzing activity of the metal oxide in the reaction. The loading of the magnesium oxide is as low as 0.1 wt% to phytosterols and far lower than the known ones. As demonstrated by the results of scanning electro-microscopy (SEM), the synergistic effect of emulsifier and magnesium oxide presumably results from elimination of nano-scale interfacial barrier between phytosterols and fatty acids and facilitation of mass transfer of reaction agents. The mild, environmentally benign, and highly effective nature of this catalytic transformation suggests its great potential applications.

    更新日期:2018-05-01
  • Phase behavior of palmitoyl and egg sphingomyelin
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-04-22
    Zoran Arsov, Emilio J. González-Ramírez, Felix M. Goñi, Stephanie Tristram-Nagle, John F. Nagle

    Despite the biological significance of sphingomyelins (SMs), there is far less structural information available for SMs compared to glycerophospholipids. Considerable confusion exists in the literature regarding even the phase behavior of SM bilayers. This work studies both palmitoyl (PSM) and egg sphingomyelin (ESM) in the temperature regime from 3 °C to 55 °C using X-ray diffraction and X-ray diffuse scattering on hydrated, oriented thick bilayer stacks. We observe clear evidence for a ripple phase for ESM in a large temperature range from 3 °C to the main phase transition temperature (TM) of ∼38 °C. This unusual stability of the ripple phase was not observed for PSM, which was in a gel phase at 3 °C, with a gel-to-ripple transition at ∼24 °C and a ripple-to-fluid transition at ∼41 °C. We also report structural results for all phases. In the gel phase at 3 °C, PSM has chains tilted by ∼30° with an area/lipid ∼45 Å2 as determined by wide angle X-ray scattering. The ripple phases for both PSM and ESM have temperature dependent ripple wavelengths that are ∼145 Å near 30 °C. In the fluid phase, our electron density profiles combined with volume measurements allow calculation of area/lipid to be ∼64 Å2 for both PSM and ESM, which is larger than that from most of the previous molecular dynamics simulations and experimental studies. Our study demonstrates that oriented lipid films are particularly well-suited to characterize ripple phases since the scattering pattern is much better resolved than in unoriented samples.

    更新日期:2018-04-25
  • Assessing Topology and Surface Orientation of an Antimicrobial Peptide Magainin 2 using Mechanically Aligned Bilayers and Electron Paramagnetic Resonance Spectroscopy
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-04-22
    Daniel J. Mayo, Indra D. Sahu, Gary A. Lorigan

    Aligned CW-EPR membrane protein samples provide additional topology interactions that are absent from conventional randomly dispersed samples. These samples are aptly suited to studying antimicrobial peptides because of their dynamic peripheral topology. In this study, four consecutive substitutions of the model antimicrobial peptide magainin 2 were synthesized and labeled with the rigid TOAC spin label. The results revealed the helical tilts to be 66° ± 5°, 76° ± 5°, 70° ± 5°, and 72° ± 5° for the TOAC substitutions H7, S8, A9, and K10 respectively. These results are consistent with previously published literature. Using the EPR (electron paramagnetic resonance) mechanical alignment technique, these substitutions were used to critically assess the topology and surface orientation of the peptide with respect to the membrane. This methodology offers a rapid and simple approach to investigate the structural topology of antimicrobial peptides.

    更新日期:2018-04-25
  • Molecular Dynamics Simulations of Glyphosate in a DPPC Lipid Bilayer ☆
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-04-21
    Ezequiel N. Frigini, J.J. López Cascales, Rodolfo D. Porasso

    Extensive Molecular Dynamics simulations have been performed to study the effect of Glyphosate (in their neutral and charged forms, GLYP and GLYP2−, respectively) on fully hydrated DiPalmitoylPhosphatidylCholine (DPPC) lipid bilayer. First, we calculated the free energy profile (using the Umbrella Sampling technique) for both states of charge of glyphosate. The minimum value for the free energy for GLYP is ∼−60 kJ.mol−1 located at z =±1.7 nm (from the lipid bilayer center), and there is almost no maximum at the center of the lipid bilayer. By contrast, the minimum for GLYP2− is ∼−35 kJ.mol−1 located at z =± 1.4 nm (from the lipid bilayer center), and the maximum reaches ∼35 kJ.mol−1 at the center of the lipid bilayer. Then, different lipid bilayer properties were analyzed for different Glyphosate:Lipid (G:L) ratios. The mean area per lipid was slightly affected, increasing only 5% (in the presence of glyphosate at high concentrations), which is in agreement with the slight decrease in deuterium order parameters. As for the thickness of the bilayer, it is observed that the state of charge produces opposite effects. On one hand, the neutral state produces an increase in the thickness of the lipid bilayer; on the other, the charged form produces a decrease in the thickness, which not depend linearly on the G:L ratios, either. The orientation of the DPPC head groups is practically unaffected throughout the range of the G:L ratios studied. Finally, the mobility of the lipids of the bilayer is strongly affected by the presence of glyphosate, considerably increasing its lateral diffusion coefficient noteworthy (one order of magnitude), with increasing G:L ratio.

    更新日期:2018-04-25
  • Morphology, compressibility and viscoelasticity of the mixed lipid monolayers in the presence of β-carotene
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-04-05
    Katarzyna Dopierała, Marta Skrzypiec

    The aim of the present study was to investigate the interfacial behaviour of model biomembranes in the presence of β-carotene (βC). The Langmuir monolayer technique was used to form the mixed lipid film at the air/water interface. Using the surface pressure-area isotherms, the surface potential-area curves and the Brewster angle microscopy the nature of interactions between carotenoid and lipid components of the monolayers was investigated. The results were obtained for complex models of the lipid bilayer composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol (CHOL). It was found that β-carotene affected the membrane stability, fluidity and rigidity, however this influence varied with the DPPC/CHOL ratio. The membrane permeability which is significant for biological functions was found to be affected by the presence of β-carotene in the membrane. The morphology of mixed films visualized by Brewster angle microscopy was similar for DPPC/CHOL and DPPC/CHOL/βC films indicating incorporation of carotenoid into the film. In contrary to previous reports for individual lipids, we did not observed the aggregation of βC in the mixed lipid monolayer. Moreover, from dilatational rheology experiment we concluded about the significant role of β-carotene in modulation of the elastic behaviour of the membrane, especially in physiologically significant surface pressure, i.e. at π = 30 mN/m.

    更新日期:2018-04-06
  • Direct carborane-peptide conjugates: Synthesis and evaluation as non-natural lipopeptide mimetics
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-03-29
    Tamara Lützenburg, Ines Neundorf, Matthias Scholz

    Herein, we report the synthesis and characterization of direct carborane-peptide conjugates. Carboranes are non-natural and extremely hydrophobic compounds and turned out to be suitable pharmacophores for diverse biological applications. In this work, we established an efficient procedure for the coupling of carboranes to peptides on solid support. We identified the coupling of carborane-1-carboxylic acids to amino groups to be superior to those with hydroxy- or sulfhydryl-groups. The carborane-peptide conjugates showed remarkably prolonged, and carborane isomer dependent chromatographic retention times. This effect can be used to generate non-natural lipopeptides with fine-tuned properties.

    更新日期:2018-03-30
  • 更新日期:2018-03-27
  • Implications of the Mediterranean diet and physical exercise on the lipid profile of metabolically healthy obese women as measured by nuclear magnetic resonance spectroscopy (1H NMR)
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-03-23
    Enrique Rodriguez-Garcia, Josefina Ruiz-Nava, Sonia Santamaria-Fernandez, Jose Carlos Fernandez-Garcia, Antonio Vargas Candela, Raquel Yahyaoui, Francisco J. Tinahones, M Rosa Bernal-Lopez, Ricardo Gomez-Huelgas

    Objective There is a lack of consensus when it comes to establishing the biochemical parameters that define metabolically healthy obese (MHO) subjects. Indeed, most studies do not include subjects’ lipid profiles. Our objective was to characterize lipoprotein size, particle and subclass concentration using 1H NMR in MHO women after two years of weight loss with a hypocaloric Mediterranean diet and physical exercise. Methods 115 non-diabetic women (aged 35-55 years) with a body mass index (BMI) of 30–40 kg/m2 and ≤1 of the following criteria: blood pressure ≥135/85 mmHg, fasting plasma glucose ≥100 mg/dL, HDL cholesterol ≤50 mg/dL and triglycerides ≥150 mg/dL were included. After two years of intensive lifestyle modification (Mediterranean diet and physical exercise), they were classified according to their weight loss: <5%, ≥5%-<10% and ≥10%. Lipoprotein size, particle and subclass concentrations were measured using 1H NMR. Results The final population, after dropouts, were 67 women (age: 44.5 ± 3.7 years, BMI: 36.3 ± 4.7 kg/m2), of whom 23 (38.3%) lost <5%, and 22 (36.7%), lost ≥5% to <10% and ≥10% of baseline body weight, respectively. The lipid profile showed no significant changes after intervention, especially in small LDL particles or in production of HDL. The diameter of LDL and HDL particles did not change after two years of a Mediterranean diet and physical exercise. Conclusion These results indicate that intensive lifestyle modification does not produce significant changes in the lipid profile of MHO women. Levels of more atherogenic or atheroprotective particles did not change after two years, despite the intervention.

    更新日期:2018-03-24
  • Niemann-Pick C2 protein regulates sterol transport between plasma membrane and late endosomes in human fibroblasts
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-03-23
    Zane Berzina, Lukasz M. Solanko, Ahmed S. Mehadi, Maria Louise V. Jensen, Frederik W. Lund, Maciej Modzel, Maria Szomek, Katarzyna A. Solanko, Alice Dupont, Gitte Krogh Nielsen, Christian W. Heegaard, Christer S. Ejsing, Daniel Wüstner

    Niemann-Pick disease type C2 is a lipid storage disorder in which mutations in the NPC2 protein cause accumulation of lipoprotein-derived cholesterol in late endosomes and lysosomes (LE/LYSs). Whether cholesterol delivered by other means to NPC2 deficient cells also accumulates in LE/LYSs is currently unknown. We show that the close cholesterol analog dehydroergosterol (DHE), when delivered to the plasma membrane (PM) accumulates in LE/LYSs of human fibroblasts lacking functional NPC2. We measured two different time scales of sterol diffusion; while DHE rich LE/LYSs moved by slow anomalous diffusion in disease cells (D ∼ 4.6∙10−4 μm2/sec; α∼0.76), a small pool of sterol could exchange rapidly with D ∼ 3 μm2/sec between LE/LYSs, as shown by fluorescence recovery after photobleaching (FRAP). By quantitative lipid mass spectrometry we found that esterification of 13C-labeled cholesterol but not of DHE is reduced 10-fold in disease fibroblasts compared to control cells. Internalized NPC2 rescued the sterol storage phenotype and strongly expanded the dynamic sterol pool seen in FRAP experiments. Together, our study shows that cholesterol esterification and trafficking of sterols between the PM and LE/LYSs depends on a functional NPC2 protein. NPC2 likely acts inside LE/LYSs from where it increases non-vesicular sterol exchange with other organelles.

    更新日期:2018-03-24
  • Surface modification of paclitaxel-loaded liposomes using d-α-tocopheryl polyethylene glycol 1000 succinate: Enhanced cellular uptake and cytotoxicity in multidrug resistant breast cancer cells
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-03-14
    Su-Min Han, Jong-Suep Baek, Min-Soo Kim, Sung-Joo Hwang, Cheong-Weon Cho

    Liposomes can achieve a controlled release and an improved bioavailability of water- insoluble drug with minimized side effects. Paclitaxel is an efficient anticancer drug for the treatment of various cancers. However, paclitaxel has a solubility of 0.5 mg/L in water and a low bioavailability of 6.5%. Moreover, paclitaxel is a substrate for p-glycoprotein, which shows a decreased accumulation of drug within the cancer cell expressed by a p-glycoprotein. Therefore, the purpose of this study is to prepare a paclitaxel-loaded liposome and evaluate the effect of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as an inhibitor of p-glycoprotein on the paclitaxel-loaded liposome. The paclitaxel-loaded liposome and TPGS coated paclitaxel-loaded liposome had spherical vesicles, with mean particle size 184.9 ± 18.45 nm with PDI 0.324 ± 0.018 and 282.6 ± 20.41 nm with PDI 0.269 ± 0.013, respectively. Paclitaxel-loaded liposome and TPGS coated paclitaxel-loaded liposome showed a controlled and sustained release of PTX over 72 hr. The cellular uptake of paclitaxel from TPGS coated paclitaxel-loaded liposome was a 3.56-fold increase for 2 h and 5.75-fold increase for 4 h compared to that from paclitaxel-loaded liposome in MCF-7/ADR cells, resulting in improved cytotoxicity against MCF-7/ADR cells. Western blot assay revealed the P-gp inhibitory effect of TPGS-coated PTX-liposome. In conclusion, TPGS coated liposome with a sustained releasing capability and the inhibitory effect of p-glycoprotein may be a promising carrier for future applications in cancer therapy.

    更新日期:2018-03-15
  • Macrophage Sphingolipids are Essential for the Entry of Mycobacteria
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-03-08
    Gopinath Viswanathan, Md. Jafurulla, G. Aditya Kumar, Tirumalai R. Raghunand, Amitabha Chattopadhyay
    更新日期:2018-03-09
  • Headgroup hydroxylation by OlsE occurs at the C4 position of ornithine lipid and is widespread in proteobacteria and bacteroidetes
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-03-07
    Georg Hölzl, Christian Sohlenkamp, Miguel Angel Vences-Guzmán, Nicolas Gisch
    更新日期:2018-03-08
  • Antioxidants inhibit low density lipoprotein oxidation less at lysosomal pH: A possible explanation as to why the clinical trials of antioxidants might have failed
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-03-05
    Feroz Ahmad, David S. Leake

    Oxidised low density lipoprotein (LDL) was considered to be important in the pathogenesis of atherosclerosis, but the large clinical trials of antioxidants, including the first one using probucol (the PQRST Trial), failed to show benefit and have cast doubt on the importance of oxidised LDL. We have shown previously that LDL oxidation can be catalysed by iron in the lysosomes of macrophages. The aim of this study was therefore to investigate the effectiveness of antioxidants in preventing LDL oxidation at lysosomal pH and also establish the possible mechanism of oxidation. Probucol did not effectively inhibit the oxidation of LDL at lysosomal pH, as measured by conjugated dienes or oxidised cholesteryl esters or tryptophan residues in isolated LDL or by ceroid formation in the lysosomes of macrophage-like cells, in marked contrast to its highly effective inhibition of LDL oxidation at pH 7.4. LDL oxidation at lysosomal pH was inhibited very effectively for long periods by N,N'-diphenyl-1,4-phenylenediamine, which is more hydrophobic than probucol and has been shown by others to inhibit atherosclerosis in rabbits, and by cysteamine, which is a hydrophilic antioxidant that accumulates in lysosomes. Iron-induced LDL oxidation might be due to the formation of the superoxide radical, which protonates at lysosomal pH to form the much more reactive, hydrophobic hydroperoxyl radical, which can enter LDL and reach its core. Probucol resides mainly in the surface monolayer of LDL and would not effectively scavenge hydroperoxyl radicals in the core of LDL. This might explain why probucol failed to protect against atherosclerosis in various clinical trials. The oxidised LDL hypothesis of atherosclerosis now needs to be re-evaluated using different and more effective antioxidants that protect against the lysosomal oxidation of LDL.

    更新日期:2018-03-06
  • DPPC Monolayer response to Non-Spanning Cobalt-cage Metallosurfactants: Electrostatic Complex Formation
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-02-27
    Lorale J. Lalgee, Leonette Cox, Richard A. Fairman, Lebert Grierson
    更新日期:2018-02-27
  • Continuous Detection of Entry of Cell-Penetrating Peptide Transportan 10 into Single Vesicles
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-02-06
    Md. Mizanur Rahman Moghal, Md. Zahidul Islam, Sabrina Sharmin, Victor Levadnyy, Md. Moniruzzaman, Masahito Yamazaki
    更新日期:2018-02-07
  • 更新日期:2018-02-02
  • Ether-linked lipids: spin-label EPR and spin echoes
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-02-02
    Maria Oranges, Rita Guzzi, Derek Marsh, Rosa Bartucci

    Electron spin echo envelope modulation (ESEEM) and conventional electron paramagnetic resonance (EPR) of site-specifically spin-labelled phospholipids are used to investigate the effect of ether-linked chains on the water-penetration and polarity profiles, as well as the phase behaviour and chain flexibility profiles, of phospholipid membranes. D2O-ESEEM reveals that water exposure of the terminal methyl groups in the interdigitated phase of dihexadecyl phosphatidylcholine (DHPC) is comparable to that of the methylene groups at the polar head-group end of the chains. Similarly, an uniform transmembrane polarity profile is obtained from the dependence of the outer 14N-hyperfine splitting on the spin-label position along the chain in frozen interdigitated DHPC dispersions. Two-component conventional EPR spectra of spin labels at the terminal methyl end of the chain reveal that the intermediate gel phase above the pretransition of DHPC contains components in which the lipid chains are interdigitated. The polarity and chain-flexibility profiles in the fluid Lα-phase of DHPC with ether-linked chains are shifted outwards, towards the polar-apolar interface, as compared with that of dihexadecanoyl phosphatidylcholine (DPPC) with ester-linked chains. Also, the polarity profile of DHPC is shifted upwards, to higher polarities. These differences reflect those in hydrocarbon thickness and area/lipid molecule reported by x-ray diffraction for the Lα-phases of the two lipids.

    更新日期:2018-02-02
  • On the quantitative phase analysis and amorphous content of triacylglycerols materials by X-ray rietveld method
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-01-31
    Guilherme A. Calligaris, Thais L.T. da Silva, Ana Paula B. Ribeiro, Adenilson O. dos Santos, Lisandro P. Cardoso
    更新日期:2018-02-02
  • Effects of electroformation protocol parameters on quality of homogeneous GUV populations
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-01-31
    Dominik Drabik, Joanna Doskocz, Magda Przybyło
    更新日期:2018-02-02
  • Renewable resources-based approach to biantennary glycolipids
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-01-31
    Mojtaba Tabandeh, Abbas Abdulameer Salman, Ean Wai Goh, Thorsten Heidelberg, Rusnah Syahila Duali Hussen
    更新日期:2018-02-02
  • Rapid Single-step Formation of Liposomes by Flow Assisted Stationary Phase Interdiffusion
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-01-31
    Chandra Has, Sopan M. Phapal, P. Sunthar
    更新日期:2018-02-02
  • Eicosapentaenoic acid and docosahexaenoic acid have distinct membrane locations and lipid interactions as determined by X-ray diffraction
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-01-31
    Samuel C.R. Sherratt, R. Preston Mason

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differentially influence lipid oxidation, signal transduction, fluidity, and cholesterol domain formation, potentially due in part to distinct membrane interactions. We used small angle x-ray diffraction to evaluate the EPA and DHA effects on membrane structure. Membrane vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol (C) (0.3C:POPC mole ratio) were prepared and treated with vehicle, EPA, or DHA (1:10 mole ratio to POPC). Electron density profiles generated from the diffraction data showed that EPA increased membrane hydrocarbon core electron density over a broad area, up to ± 20 Å from the membrane center, indicating an energetically favorable extended orientation for EPA likely stabilized by van der Waals interactions. By contrast, DHA increased electron density in the phospholipid head group region starting at ± 12 Å from the membrane center, presumably due to DHA-surface interactions, with coincident reduction in electron density in the membrane hydrocarbon core centered ± 7–9 Å from the membrane center. The membrane width (d-space) decreased by 5 Å in the presence of vehicle as the temperature increased from 10 °C to 30 °C due to increased acyl chain trans-gauche isomerizations, which was unaffected by addition of EPA or DHA. The influence of DHA on membrane structure was modulated by temperature changes while the interactions EPA were unaffected. The contrasting EPA and DHA effects on membrane structure indicate distinct molecular locations and orientations that may contribute to observed differences in biological activity.

    更新日期:2018-02-02
  • Perdeuteration of cholesterol for neutron scattering applications using recombinant Pichia pastoris
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-01-31
    Martine Moulin, Gernot A. Strohmeier, Melanie Hirz, Katherine C. Thompson, Adrian R. Rennie, Richard A. Campbell, Harald Pichler, Selma Maric, V. Trevor Forsyth, Michael Haertlein

    Deuteration of biomolecules has a great impact on both quality and scope of neutron scattering experiments. Cholesterol is a major component of mammalian cells, where it plays a critical role in membrane permeability, rigidity and dynamics, and contributes to specific membrane structures such as lipid rafts. Cholesterol is the main cargo in low and high-density lipoprotein complexes (i.e. LDL, HDL) and is directly implicated in several pathogenic conditions such as coronary artery disease which leads to 17 million deaths annually. Neutron scattering studies on membranes or lipid-protein complexes exploiting contrast variation have been limited by the lack of availability of fully deuterated biomolecules and especially perdeuterated cholesterol. The availability of perdeuterated cholesterol provides a unique way of probing the structural and dynamical properties of the lipoprotein complexes that underly many of these disease conditions. Here we describe a procedure for in vivo production of perdeuterated recombinant cholesterol in lipid-engineered Pichia pastoris. Using flask and fed-batch fermenter cultures in deuterated minimal medium perdeuteration of the purified cholesterol was verified by mass spectrometry and its use in a neutron scattering study was demonstrated using neutron reflectometry.

    更新日期:2018-02-02
  • Langmuir-Monolayer Methodologies for Characterizing Protein-Lipid Interactions
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-01-31
    Mohamed Elderdfi, Aleksander F. Sikorski

    The Langmuir-monolayer technique is a convenient method that allows for continuous control over several membrane-specific parameters, such as molecular packing, physical states, lateral pressure and lipid composition. Lipid monolayers are well suited for applications involving the Langmuir-monolayer technique: they are very well-defined, stable, homogeneous and two-dimensional, and they have planar geometry. In this review, some features of monolayer methodologies based on the Langmuir-monolayer technique are described, with a focus on the step-wise procedures that can be applied to characterize protein-lipid interactions at the lipid monolayer/buffer interface in order to maximize the information concerning the mechanism of interaction between the protein and the lipid monolayer.

    更新日期:2018-02-02
  • C24-hydroxylated stigmastane derivatives as Liver X Receptor agonists
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-01-17
    Francisco Fermin Castro Navas, Gianluca Giorgi, Daniela Maggioni, Manuela Pacciarini, Vincenzo Russo, Maura Marinozzi

    Phytosterols are stucturally correlated to the endogenous ligands of Liver X Receptor (LXR), a ligand-activated nuclear receptor that has emerged as an attractive drug target due to its ability to integrate metabolic and inflammatory signaling. Natural and semi-synthetic phytosterol derivatives characterized by the presence of side-chain oxygenated functions have shown to be able to modulate LXR activity. Here, we describe the efficient synthesis of four stigmastane derivatives, endowed with a hydroxyl group at C24 position, namely (24R)- and (24S)-stigmasta-5,28-diene-3β,24-ols (also referred to as saringosterols, 10a and 10b) and (24R)- and (24S)-stigmasta-5-ene-3β,24-ols (11a and 11b), starting from the readily available stigmasterol. Thanks to X-ray crystallography the absolute configuration of the newly created chiral centers was definitively assigned for all the four compounds. The subsequent luciferase assays with GAL-4 chimeric receptors evidenced the ability of the two 24(S)-epimers, 10b and 11b, to interact with LXRs, showing the same degree of affinity as (22R)-hydroxycholesterol (1). With regard to the isoform selectivity both the derivatives 10b and 11b showed a preference for LXRβ, up to 4-fold in terms of efficacy for 11b. The gene expression profiling of (24S)-stigmasta-5,28-diene-3β,24-ol (10a) and (24S)-stigmasta-5-ene-3β,24-ol (11a) demonstrated the capability of both the compounds to induce the expression of four well-known LXR target genes, such as ABCA1, SREBP1c, FASN, and SCD1 in U937 monocytic cell line, thus supporting the hypothesis they were LXR positive modulators.

    更新日期:2018-01-17
  • 更新日期:2018-01-12
  • Novel lipids with three C18-fatty acid chains and an amino acid head group for pH-responsive and sustained antibiotic delivery
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2018-01-02
    Mahantesh Jadhav, Rahul S. Kalhapure, Sanjeev Rambharose, Chunderika Mocktar, Sanil Singh, Tetsuya Kodama, Thirumala Govender
    更新日期:2018-01-03
  • Molecule confirmation and structure characterization of pentatriacontatrienyl mycolate in Mycobacterium smegmatis
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2017-12-30
    Marta Llorens-Fons, Esther Julián, Marina Luquin, Míriam Pérez-Trujillo

    Mycobacterium smegmatis is often used to study the different components of mycobacterial cell wall. Mycolic acids are important components of mycobacterial cell wall that have been associated with virulence. Recently, a novel lipid containing mycolic acids has been described in M. smegmatis. However, some uncertainties regarding the structure of this molecule named mycolate ester wax have been reported. The objective of this work was to perform an in depth structural study of this molecule for its precise characterization. Using 1H and 13C NMR spectroscopy, the molecular structure of mycolate ester wax found in M. smegmatis has been elucidated. The characterization was complemented with MS analyses. This molecule is formed by a carbon chain with three methyl substituted olefinic units and a mycolate structure with trans double bonds and cis cyclopropane rings. The present molecular study will facilitate the detection and identification of pentatriacontatrienyl mycolate in future studies by the performance of a simple 1D 1H NMR experiment.

    更新日期:2017-12-31
  • Structural design of intrinsically fluorescent oxysterols
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2017-12-26
    Lina J. Nåbo, Maciej Modzel, Kathiresan Krishnan, Douglas F. Covey, Hideji Fujiwara, Daniel S. Ory, Maria Szomek, Himanshu Khandelia, Daniel Wüstner, Jacob Kongsted

    Oxysterols are oxidized derivatives of cholesterol with many important biological functions. Trafficking of oxysterols in and between cells is not well studied, largely due to the lack of appropriate oxysterol analogs. Intrinsically fluorescent oxysterols present a new route towards direct observation of intracellular oxysterol trafficking by fluorescence microscopy. We characterize the fluorescence properties of the existing fluorescent 25-hydroxycholesterol analog 25-hydroxycholestatrienol, and propose a new probe with an extended conjugated system. The location of both probes inside a membrane is analyzed and compared with that of 25-hydroxycholesterol using molecular dynamics simulations. The analogs’ one- and two-photon absorption properties inside the membrane are evaluated using electronic structure calculations with polarizable embedding. Due to predicted keto–enol tautomerisation of the new oxysterol analog, we also evaluate the keto form. Both analogs are found to be good probe candidates for 25-hydroxycholesterol, provided that the new analog remains in the enol-form. Only the new analog with extended conjugated system shows significant two-photon absorption, which is strongly enhanced by the presence of the membrane.

    更新日期:2017-12-27
  • Local Anesthetics Induce Interdigitation and Thermotropic Changes in Dipalmitoylphosphatidylcholine Bilayers
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2017-12-21
    S. Thirupathi Reddy, Sandeep Shrivastava, Amitabha Chattopadhyay
    更新日期:2017-12-22
  • Cobalt and Nickel Affect the Fluidity of Negatively-Charged Biomimetic Membranes
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2017-12-13
    Jenelle Umbsaar, Evan Kerek, Elmar J. Prenner
    更新日期:2017-12-14
  • Uptake of Iron (III)-Ethylenediamine-N, N, N′, N′-tetraacetic Acid Complex by Phosphatidylcholine Lipid Film Part II. Effect of Film Curvature
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2017-12-11
    Masumi Villeneuve, Mihoko Tanaka, Natsumi Saito, Hiroyasu Sakamoto, Yoshiteru Hayami
    更新日期:2017-12-14
  • Phase behavior in the biologically important oleic acid/sodium oleate/water system
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2017-12-02
    Stefania Mele, Olle Söderman, Helena Ljusberg-Wahrén, Krister Thuresson, Maura Monduzzi, Tommy Nylander
    更新日期:2017-12-14
  • Ion-induced modification of the sucrose network and its impact on melting of freeze-dried liposomes. DSC and molecular dynamics study
    Chem. Phys. Lipids (IF 2.766) Pub Date : 2017-11-24
    Danijela Bakarić, Dražen Petrov, Yamuna Kunhi Mouvenchery, Stefan Heiβler, Chris Oostenbrink, Gabriele E. Schaumann
    更新日期:2017-12-14
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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