Lipid insightsPub Date : 2019-01-05eCollection Date: 2019-01-01DOI: 10.1177/1178635318820923
Andrea C Cutro, E Anibal Disalvo, María A Frías
{"title":"Effects of Phenylalanine on the Liquid-Expanded and Liquid-Condensed States of Phosphatidylcholine Monolayers.","authors":"Andrea C Cutro, E Anibal Disalvo, María A Frías","doi":"10.1177/1178635318820923","DOIUrl":"https://doi.org/10.1177/1178635318820923","url":null,"abstract":"<p><strong>Background: </strong>Phenylalanine (Phe) is involved in physiological and pathological processes in cell membranes in which expanded and condensed states coexist. In this direction, it was reported that surface hydration is important for the binding affinity of the amino acid which significantly perturbs 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine (DPPC) monolayer structure and morphology. A deeper insight showed that Phe inserts in DPPC monolayer defects as a monomer at pH 5 and forms aggregates that adsorb to the membrane surface generating a reconfiguration of the lipid arrangement in areas of higher packing. This new arrangement in the monolayer causes the reorientation of dipoles of lipid and water molecules which is congruent with the dehydration and surface tension changes reported above. With this background, this article studies the affinity of Phe in liquid-expanded 1,2-dimyristoyl-<i>sn</i>-glycero-3 phosphocholine (LE DMPC) and liquid-condensed 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine (LC DPPC) monolayers and their effects on membrane properties.</p><p><strong>Results: </strong>The adsorption of Phe can be described by a cooperative process in non-independent sites suggesting that Phe/lipid systems reorganize to form new structures at a high degree of coverage. Compressibility modulus and Brewster angle microscopy (BAM) images allow to propose that Phe causes a new phase in 1,2-dimyristoyl-<i>sn</i>-glycero-3 phosphocholine (DMPC) and DPPC.</p><p><strong>Conclusions: </strong>Phe imposes new arrangements in the lipid phase to form new structures with different compressibility behavior than lipid binary mixtures of DMPC and DPPC. Phe interaction with the LC and LE phases gives place to a process in which a synergistic effect between non-independent sites can be produced. These features of Phe/lipid interaction would be of great importance to understand the multiple effects of Phe on cell membranes.</p>","PeriodicalId":18039,"journal":{"name":"Lipid insights","volume":"12 ","pages":"1178635318820923"},"PeriodicalIF":0.0,"publicationDate":"2019-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178635318820923","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36854048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipid insightsPub Date : 2018-02-14eCollection Date: 2018-01-01DOI: 10.1177/1178635317754071
Avia Rosenhouse-Dantsker
{"title":"Cholesterol-Binding Sites in GIRK Channels: The Devil is in the Details.","authors":"Avia Rosenhouse-Dantsker","doi":"10.1177/1178635317754071","DOIUrl":"https://doi.org/10.1177/1178635317754071","url":null,"abstract":"<p><p>In recent years, it has become evident that cholesterol plays a direct role in the modulation of a variety of ion channels. In most cases, cholesterol downregulates channel activity. In contrast, our earlier studies have demonstrated that atrial G protein inwardly rectifying potassium (GIRK) channels are upregulated by cholesterol. Recently, we have shown that hippocampal GIRK currents are also upregulated by cholesterol. A combined computational-experimental approach pointed to putative cholesterol-binding sites in the transmembrane domain of the GIRK2 channel, the primary subunit in hippocampal GIRK channels. In particular, the principal cholesterol-binding site was located in the center of the transmembrane domain in between the inner and outer α-helices of 2 adjacent subunits. Further studies pointed to a similar cholesterol-binding site in GIRK4, a major subunit in atrial GIRK channels. However, a close look at a sequence alignment of the transmembrane helices of the 2 channels reveals surprising differences among the residues that interact with the cholesterol molecule in these 2 channels. Here, we compare the residues that form putative cholesterol-binding sites in GIRK2 and GIRK4 and discuss the similarities and differences among them.</p>","PeriodicalId":18039,"journal":{"name":"Lipid insights","volume":"11 ","pages":"1178635317754071"},"PeriodicalIF":0.0,"publicationDate":"2018-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178635317754071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35851910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipid insightsPub Date : 2017-12-15eCollection Date: 2017-01-01DOI: 10.1177/1178635317747281
Martijn R Molenaar, Arie B Vaandrager, J Bernd Helms
{"title":"Some Lipid Droplets Are More Equal Than Others: Different Metabolic Lipid Droplet Pools in Hepatic Stellate Cells.","authors":"Martijn R Molenaar, Arie B Vaandrager, J Bernd Helms","doi":"10.1177/1178635317747281","DOIUrl":"https://doi.org/10.1177/1178635317747281","url":null,"abstract":"<p><p>Hepatic stellate cells (HSCs) are professional lipid-storing cells and are unique in their property to store most of the retinol (vitamin A) as retinyl esters in large-sized lipid droplets. Hepatic stellate cell activation is a critical step in the development of chronic liver disease, as activated HSCs cause fibrosis. During activation, HSCs lose their lipid droplets containing triacylglycerols, cholesteryl esters, and retinyl esters. Lipidomic analysis revealed that the dynamics of disappearance of these different classes of neutral lipids are, however, very different from each other. Although retinyl esters steadily decrease during HSC activation, triacylglycerols have multiple pools one of which becomes transiently enriched in polyunsaturated fatty acids before disappearing. These observations are consistent with the existence of preexisting \"original\" lipid droplets with relatively slow turnover and rapidly recycling lipid droplets that transiently appear during activation of HSCs. Elucidation of the molecular machinery involved in the regulation of these distinct lipid droplet pools may open new avenues for the treatment of liver fibrosis.</p>","PeriodicalId":18039,"journal":{"name":"Lipid insights","volume":"10 ","pages":"1178635317747281"},"PeriodicalIF":0.0,"publicationDate":"2017-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178635317747281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35687367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipid insightsPub Date : 2017-12-13eCollection Date: 2017-01-01DOI: 10.1177/1178635317745518
Stefano Vanni
{"title":"Intracellular Lipid Droplets: From Structure to Function.","authors":"Stefano Vanni","doi":"10.1177/1178635317745518","DOIUrl":"https://doi.org/10.1177/1178635317745518","url":null,"abstract":"<p><p>Lipid droplets (LDs) are unique intracellular organelles that are mainly constituted by neutral lipids (triglycerides, sterol esters). As such they serve as the main site of energy storage in the cell and they are akin to oil emulsions in water. To prevent the direct exposure of the hydrophobic neutral lipids to the aqueous environment of the cytosol, LDs are surrounded by a monolayer of phospholipids that thus behave as a natural surfactant. This interfacial structure is rather unique inside the cell, but a molecular understanding of how the LD structure modulates its functions is still lacking, mainly due to technical challenges in both experimental and computational approaches to investigate oil-in-water emulsions. Recently, we have investigated the structure of LDs using a combination of existing and newly developed computational approaches that are optimized to study oil-water interfaces.<sup>1</sup> Our simulations provide a comprehensive molecular characterization of the unique surface properties of LDs, suggesting structure-function relationship in several LD-related metabolic processes.</p>","PeriodicalId":18039,"journal":{"name":"Lipid insights","volume":"10 ","pages":"1178635317745518"},"PeriodicalIF":0.0,"publicationDate":"2017-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178635317745518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35681457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipid insightsPub Date : 2016-11-28DOI: 10.4137/LPI.S40597
P. Oelkers, K. Pokhrel
{"title":"Four Acyltransferases Uniquely Contribute to Phospholipid Heterogeneity in Saccharomyces cerevisiae","authors":"P. Oelkers, K. Pokhrel","doi":"10.4137/LPI.S40597","DOIUrl":"https://doi.org/10.4137/LPI.S40597","url":null,"abstract":"Diverse acyl‐CoA species and acyltransferase isoenzymes are part of a complex system that synthesizes glycerophospholipids and triacylglycerols. Saccharomyces cerevisiae, having four main acyl‐CoA species, two main glycerol‐3‐phosphate 1‐O‐acyltransferases (Gat1p, Gat2p) and two main 1‐acylglycerol‐3‐phosphate O‐acyltransferases (Lpt1p, Slc1p), provides an experimental system of reduced complexity. To comprehensively examine the in vivo contribution of the acyltransferase isoenzymes to phospholipid heterogeneity, haploid yeast with compound mutations were generated: gat1Δlpt1Δ, gat2Δlpt1Δ, gat1Δslc1Δ, and gat2Δslc1Δ. All mutations mildly reduced [3H]palmitic acid incorporation into phospholipids relative to triacylglycerol. Electrospray ionization tandem mass spectrometry analysis of phospholipids identified few differences from wild type in gat1Δlpt1Δ, dramatic differences in gat2Δslc1Δ, and intermediate changes in the other two mutants. The gat2Δslc1Δ yeast, solely expressing Gat1p and Lpt1p, had phospholipids with 10% more unsaturated acyl chains and 20% fewer species with 34 acyl chain carbons. These percent changes varied among phospholipid head group species. Thus, the combined activities of Gat2p and Slc1p seem to promote the production of phospholipids with “mixed” chain lengths (e.g. 16 and 18 carbons). This is particularly true for phosphatidylserine. Head group allocation was also affected in gat2Δslc1Δ yeast which had 15% more phosphatidylethanolamine, 38% less phosphatidylserine, and 85% less phosphatidylglycerol. These alterations slowed growth in rich media at 30 °C by 18% but not in media with non‐fermentable carbon sources. Growth was abrogated in rich media at 18.5 °C or containing 10% ethanol. Therefore, Gat2p and Slc1p primarily dictate appropriate phospholipid acyl chain composition, presumably through de novo synthesis, in several growth conditions. This composition is likely steered by Slc1p selectively pairing acyl chains of different lengths.","PeriodicalId":18039,"journal":{"name":"Lipid insights","volume":"54 1","pages":"31 - 41"},"PeriodicalIF":0.0,"publicationDate":"2016-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83148490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipid insightsPub Date : 2016-11-14DOI: 10.4137/LPI.S37450
Jonathan T. Davies, Spencer Delfino, Chad E. Feinberg, Meghan Johnson, Veronica L. Nappi, Joshua T. Olinger, Anthony P. Schwab, H. Swanson
{"title":"Current and Emerging Uses of Statins in Clinical Therapeutics: A Review","authors":"Jonathan T. Davies, Spencer Delfino, Chad E. Feinberg, Meghan Johnson, Veronica L. Nappi, Joshua T. Olinger, Anthony P. Schwab, H. Swanson","doi":"10.4137/LPI.S37450","DOIUrl":"https://doi.org/10.4137/LPI.S37450","url":null,"abstract":"Statins, a class of cholesterol-lowering medications that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, are commonly administered to treat atherosclerotic cardiovascular disease. Statin use may expand considerably given its potential for treating an array of cholesterol-independent diseases. However, the lack of conclusive evidence supporting these emerging therapeutic uses of statins brings to the fore a number of unanswered questions including uncertainties regarding patient-to-patient variability in response to statins, the most appropriate statin to be used for the desired effect, and the efficacy of statins in treating cholesterol-independent diseases. In this review, the adverse effects, costs, and drug–drug and drug–food interactions associated with statin use are presented. Furthermore, we discuss the pleiotropic effects associated with statins with regard to the onset and progression of autoimmune and inflammatory diseases, cancer, neurodegenerative disorders, strokes, bacterial infections, and human immunodeficiency virus. Understanding these issues will improve the prognosis of patients who are administered statins and potentially expand our ability to treat a wide variety of diseases.","PeriodicalId":18039,"journal":{"name":"Lipid insights","volume":"18 1","pages":"13 - 29"},"PeriodicalIF":0.0,"publicationDate":"2016-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74048192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipid insightsPub Date : 2016-09-07DOI: 10.4137/LPI.S40233
V. Patel, Gerard G. Dumancas, Lakshmi C. Kasi Viswanath, Randall D. Maples, B. J. J. Subong
{"title":"Castor Oil: Properties, Uses, and Optimization of Processing Parameters in Commercial Production","authors":"V. Patel, Gerard G. Dumancas, Lakshmi C. Kasi Viswanath, Randall D. Maples, B. J. J. Subong","doi":"10.4137/LPI.S40233","DOIUrl":"https://doi.org/10.4137/LPI.S40233","url":null,"abstract":"Castor oil, produced from castor beans, has long been considered to be of important commercial value primarily for the manufacturing of soaps, lubricants, and coatings, among others. Global castor oil production is concentrated primarily in a small geographic region of Gujarat in Western India. This region is favorable due to its labor-intensive cultivation method and subtropical climate conditions. Entrepreneurs and castor processors in the United States and South America also cultivate castor beans but are faced with the challenge of achieving high castor oil production efficiency, as well as obtaining the desired oil quality. In this manuscript, we provide a detailed analysis of novel processing methods involved in castor oil production. We discuss novel processing methods by explaining specific processing parameters involved in castor oil production.","PeriodicalId":18039,"journal":{"name":"Lipid insights","volume":"9 1","pages":"1 - 12"},"PeriodicalIF":0.0,"publicationDate":"2016-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86983818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipid insightsPub Date : 2016-06-09eCollection Date: 2015-01-01DOI: 10.4137/LPI.S31617
Katarzyna A Solanko, Maciej Modzel, Lukasz M Solanko, Daniel Wüstner
{"title":"Fluorescent Sterols and Cholesteryl Esters as Probes for Intracellular Cholesterol Transport.","authors":"Katarzyna A Solanko, Maciej Modzel, Lukasz M Solanko, Daniel Wüstner","doi":"10.4137/LPI.S31617","DOIUrl":"https://doi.org/10.4137/LPI.S31617","url":null,"abstract":"<p><p>Cholesterol transport between cellular organelles comprised vesicular trafficking and nonvesicular exchange; these processes are often studied by quantitative fluorescence microscopy. A major challenge for using this approach is producing analogs of cholesterol with suitable brightness and structural and chemical properties comparable with those of cholesterol. This review surveys currently used fluorescent sterols with respect to their behavior in model membranes, their photophysical properties, as well as their transport and metabolism in cells. In the first part, several intrinsically fluorescent sterols, such as dehydroergosterol or cholestatrienol, are discussed. These polyene sterols (P-sterols) contain three conjugated double bonds in the steroid ring system, giving them slight fluorescence in ultraviolet light. We discuss the properties of P-sterols relative to cholesterol, outline their chemical synthesis, and explain how to image them in living cells and organisms. In particular, we show that P-sterol esters inserted into low-density lipoprotein can be tracked in the fibroblasts of Niemann-Pick disease using high-resolution deconvolution microscopy. We also describe fluorophore-tagged cholesterol probes, such as BODIPY-, NBD-, Dansyl-, or Pyrene-tagged cholesterol, and eventual esters of these analogs. Finally, we survey the latest developments in the synthesis and use of alkyne cholesterol analogs to be labeled with fluorophores by click chemistry and discuss the potential of all approaches for future applications. </p>","PeriodicalId":18039,"journal":{"name":"Lipid insights","volume":"8 Suppl 1","pages":"95-114"},"PeriodicalIF":0.0,"publicationDate":"2016-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/LPI.S31617","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34601099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipid insightsPub Date : 2016-04-27eCollection Date: 2015-01-01DOI: 10.4137/LPI.S31616
Pentti Somerharju
{"title":"Is Spontaneous Translocation of Polar Lipids Between Cellular Organelles Negligible?","authors":"Pentti Somerharju","doi":"10.4137/LPI.S31616","DOIUrl":"https://doi.org/10.4137/LPI.S31616","url":null,"abstract":"<p><p>In most reviews addressing intracellular lipid trafficking, spontaneous diffusion of lipid monomers between the cellular organelles is considered biologically irrelevant because it is thought to be far too slow to significantly contribute to organelle biogenesis. This view is based on intervesicle transfer experiments carried out in vitro with few lipids as well as on the view that lipids are highly hydrophobic and thus cannot undergo spontaneous intermembrane diffusion at a significant rate. However, besides that single-chain lipids can translocate between vesicles in seconds, it has been demonstrated that the rate of spontaneous transfer of two-chain polar lipids can vary even 1000-fold, depending on the number of carbons and double bonds in the acyl chains. In addition, the rate of spontaneous lipid transfer can strongly depend on the experimental conditions such as vesicle composition and concentration. This review examines the studies suggesting that spontaneous lipid transfer is probably more relevant to intracellular trafficking of amphipathic lipids than commonly thought. </p>","PeriodicalId":18039,"journal":{"name":"Lipid insights","volume":"8 Suppl 1","pages":"87-93"},"PeriodicalIF":0.0,"publicationDate":"2016-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/LPI.S31616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34521202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipid insightsPub Date : 2016-04-06eCollection Date: 2015-01-01DOI: 10.4137/LPI.S31781
Suriakarthiga Ganesan, Brittney N Shabits, Vanina Zaremberg
{"title":"Tracking Diacylglycerol and Phosphatidic Acid Pools in Budding Yeast.","authors":"Suriakarthiga Ganesan, Brittney N Shabits, Vanina Zaremberg","doi":"10.4137/LPI.S31781","DOIUrl":"https://doi.org/10.4137/LPI.S31781","url":null,"abstract":"<p><p>Phosphatidic acid (PA) and diacylglycerol (DAG) are key signaling molecules and important precursors for the biosynthesis of all glycerolipids found in eukaryotes. Research conducted in the model organism Saccharomyces cerevisiae has been at the forefront of the identification of the enzymes involved in the metabolism and transport of PA and DAG. Both these lipids can alter the local physical properties of membranes by introducing negative curvature, but the anionic nature of the phosphomonoester headgroup in PA sets it apart from DAG. As a result, the mechanisms underlying PA and DAG interaction with other lipids and proteins are notoriously different. This is apparent from the analysis of the protein domains responsible for recognition and binding to each of these lipids. We review the current evidence obtained using the PA-binding proteins and domains fused to fluorescent proteins for in vivo tracking of PA pools in yeast. In addition, we present original results for visualization of DAG pools in yeast using the C1 domain from mammalian PKCδ. An emerging first cellular map of the distribution of PA and DAG pools in actively growing yeast is discussed. </p>","PeriodicalId":18039,"journal":{"name":"Lipid insights","volume":"8 Suppl 1","pages":"75-85"},"PeriodicalIF":0.0,"publicationDate":"2016-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/LPI.S31781","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34406270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}