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Sample records for intracellular lipid storage

  1. Polycyclic aromatic hydrocarbons storage by Fusarium solani in intracellular lipid vesicles

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    Verdin, Anthony [Laboratoire de Mycologie/Phytopathologie/Environnement, Universite du Littoral-Cote d' Opale, 17 avenue Bleriot, BP 699, 62228 Calais Cedex (France); Lounes-Hadj Sahraoui, Anissa [Laboratoire de Mycologie/Phytopathologie/Environnement, Universite du Littoral-Cote d' Opale, 17 avenue Bleriot, BP 699, 62228 Calais Cedex (France)]. E-mail: lounes@univ-littoral.fr; Newsam, Ray [Department of Biosciences, University of Kent, Canterbury CT2 7NJ (United Kingdom); Robinson, Gary [Department of Biosciences, University of Kent, Canterbury CT2 7NJ (United Kingdom); Durand, Roger [Laboratoire de Mycologie/Phytopathologie/Environnement, Universite du Littoral-Cote d' Opale, 17 avenue Bleriot, BP 699, 62228 Calais Cedex (France)

    2005-01-01

    Accumulation and elimination of polycyclic aromatic hydrocarbons (PAHs) were studied in the fungus Fusarium solani. When the fungus was grown on a synthetic medium containing benzo[a]pyrene, hyphae of F. solani contained numerous lipid vesicles which could be stained by the lipid-specific dyes: Sudan III and Rhodamine B. The fluorescence produced by Rhodamine B and PAH benzo[a]pyrene were at the same locations in the fungal hyphae, indicating that F. solani stored PAH in pre-existing lipid vesicles. A passive temperature-independent process is involved in the benzo[a]pyrene uptake and storage. Sodium azide, a cytochrome c oxidation inhibitor, and the two cytoskeleton inhibitors colchicine and cytochalasin did not prevent the transport and accumulation of PAH in lipid vesicles of F. solani hyphae. F. solani degraded a large range of PAHs at different rates. PAH intracellular storage in lipid vesicles was not necessarily accompanied by degradation and was common to numerous other fungi. - Fungi can store PAHs intracellularly in lipid vesicles independently of their PAH degradation abilities.

  2. Polycyclic aromatic hydrocarbons storage by Fusarium solani in intracellular lipid vesicles

    International Nuclear Information System (INIS)

    Verdin, Anthony; Lounes-Hadj Sahraoui, Anissa; Newsam, Ray; Robinson, Gary; Durand, Roger

    2005-01-01

    Accumulation and elimination of polycyclic aromatic hydrocarbons (PAHs) were studied in the fungus Fusarium solani. When the fungus was grown on a synthetic medium containing benzo[a]pyrene, hyphae of F. solani contained numerous lipid vesicles which could be stained by the lipid-specific dyes: Sudan III and Rhodamine B. The fluorescence produced by Rhodamine B and PAH benzo[a]pyrene were at the same locations in the fungal hyphae, indicating that F. solani stored PAH in pre-existing lipid vesicles. A passive temperature-independent process is involved in the benzo[a]pyrene uptake and storage. Sodium azide, a cytochrome c oxidation inhibitor, and the two cytoskeleton inhibitors colchicine and cytochalasin did not prevent the transport and accumulation of PAH in lipid vesicles of F. solani hyphae. F. solani degraded a large range of PAHs at different rates. PAH intracellular storage in lipid vesicles was not necessarily accompanied by degradation and was common to numerous other fungi. - Fungi can store PAHs intracellularly in lipid vesicles independently of their PAH degradation abilities

  3. Lysosomal lipid storage diseases.

    Science.gov (United States)

    Schulze, Heike; Sandhoff, Konrad

    2011-06-01

    Lysosomal lipid storage diseases, or lipidoses, are inherited metabolic disorders in which typically lipids accumulate in cells and tissues. Complex lipids, such as glycosphingolipids, are constitutively degraded within the endolysosomal system by soluble hydrolytic enzymes with the help of lipid binding proteins in a sequential manner. Because of a functionally impaired hydrolase or auxiliary protein, their lipid substrates cannot be degraded, accumulate in the lysosome, and slowly spread to other intracellular membranes. In Niemann-Pick type C disease, cholesterol transport is impaired and unesterified cholesterol accumulates in the late endosome. In most lysosomal lipid storage diseases, the accumulation of one or few lipids leads to the coprecipitation of other hydrophobic substances in the endolysosomal system, such as lipids and proteins, causing a "traffic jam." This can impair lysosomal function, such as delivery of nutrients through the endolysosomal system, leading to a state of cellular starvation. Therapeutic approaches are currently restricted to mild forms of diseases with significant residual catabolic activities and without brain involvement.

  4. Lipid storage myopathies.

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    Bruno, Claudio; Dimauro, Salvatore

    2008-10-01

    The aim of this review is to provide an update on disorders of lipid metabolism affecting skeletal muscle exclusively or predominantly and to summarize recent clinical, genetic, and therapeutic studies in this field. Over the past 5 years, new clinical phenotypes and genetic loci have been described, unusual pathogenic mechanisms have been elucidated, and novel pharmacological approaches have been developed. At least one genetic defect responsible for the myopathic form of CoQ10 deficiency has been identified, causing a disorder that is allelic with the late-onset riboflavine-responsive form of multiple acyl-coenzyme A dehydrogenation deficiency. Novel mechanisms involved in the lipolytic breakdown of cellular lipid depots have been described and have led to the identification of genes and mutations responsible for multisystemic neutral lipid storage disorders, characterized by accumulation of triglyceride in multiple tissues, including muscle. Defects in lipid metabolism can affect either the mitochondrial transport and oxidation of exogenous fatty acid or the catabolism of endogenous triglycerides. These disorders impair energy production and almost invariably involve skeletal muscle, causing progressive myopathy with muscle weakness, or recurrent acute episodes of rhabdomyolysis triggered by exercise, fasting, or infections. Clinical and genetic characterization of these disorders has important implications both for accurate diagnostic approach and for development of therapeutic strategies.

  5. LIPID SYNTHESIS, INTRACELLULAR TRANSPORT, AND SECRETION

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    Stein, Olga; Stein, Yechezkiel

    1967-01-01

    In the mammary glands of lactating albino mice injected intravenously with 9, 10-oleic acid-3H or 9, 10-palmitic acid-3H, it has been shown that the labeled fatty acids are incorporated into mammary gland glycerides. The labeled lipid in the mammary gland 1 min after injection was in esterified form (> 95%), and the radioautographic reaction was seen over the rough endoplasmic reticulum and over lipid droplets, both intracellular and intraluminal. At 10–60 min after injection, the silver grains were concentrated predominantly over lipid droplets. There was no concentration of radioactivity over the granules in the Golgi apparatus, at any time interval studied. These findings were interpreted to indicate that after esterification of the fatty acid into glycerides in the rough endoplasmic reticulum an in situ aggregation of lipid occurs, with acquisition of droplet form. The release of the lipid into the lumen proceeds directly and not through the Golgi apparatus, in contradistinction to the mode of secretion of casein in the mammary gland or of lipoprotein in the liver. The presence of strands of endoplasmic reticulum attached to intraluminal lipid droplets provides a structural counterpart to the milk microsomes described in ruminant milk. PMID:6033535

  6. Neuroimaging of Lipid Storage Disorders

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    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…

  7. Host lipid droplets: An important source of lipids salvaged by the intracellular parasite Toxoplasma gondii.

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    Sabrina J Nolan

    2017-06-01

    Full Text Available Toxoplasma is an obligate intracellular parasite that replicates in mammalian cells within a parasitophorous vacuole (PV that does not fuse with any host organelles. One mechanism developed by the parasite for nutrient acquisition is the attraction of host organelles to the PV. Here, we examined the exploitation of host lipid droplets (LD, ubiquitous fat storage organelles, by Toxoplasma. We show that Toxoplasma replication is reduced in host cells that are depleted of LD, or impaired in TAG lipolysis or fatty acid catabolism. In infected cells, the number of host LD and the expression of host LD-associated genes (ADRP, DGAT2, progressively increase until the onset of parasite replication. Throughout infection, the PV are surrounded by host LD. Toxoplasma is capable of accessing lipids stored in host LD and incorporates these lipids into its own membranes and LD. Exogenous addition of oleic acid stimulates LD biogenesis in the host cell and results in the overaccumulation of neutral lipids in very large LD inside the parasite. To access LD-derived lipids, Toxoplasma intercepts and internalizes within the PV host LD, some of which remaining associated with Rab7, which become wrapped by an intravacuolar network of membranes (IVN. Mutant parasites impaired in IVN formation display diminished capacity of lipid uptake from host LD. Moreover, parasites lacking an IVN-localized phospholipase A2 are less proficient in salvaging lipids from host LD in the PV, suggesting a major contribution of the IVN for host LD processing in the PV and, thus lipid content release. Interestingly, gavage of parasites with lipids unveils, for the first time, the presence in Toxoplasma of endocytic-like structures containing lipidic material originating from the PV lumen. This study highlights the reliance of Toxoplasma on host LD for its intracellular development and the parasite's capability in scavenging neutral lipids from host LD.

  8. Host lipid droplets: An important source of lipids salvaged by the intracellular parasite Toxoplasma gondii.

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    Nolan, Sabrina J; Romano, Julia D; Coppens, Isabelle

    2017-06-01

    Toxoplasma is an obligate intracellular parasite that replicates in mammalian cells within a parasitophorous vacuole (PV) that does not fuse with any host organelles. One mechanism developed by the parasite for nutrient acquisition is the attraction of host organelles to the PV. Here, we examined the exploitation of host lipid droplets (LD), ubiquitous fat storage organelles, by Toxoplasma. We show that Toxoplasma replication is reduced in host cells that are depleted of LD, or impaired in TAG lipolysis or fatty acid catabolism. In infected cells, the number of host LD and the expression of host LD-associated genes (ADRP, DGAT2), progressively increase until the onset of parasite replication. Throughout infection, the PV are surrounded by host LD. Toxoplasma is capable of accessing lipids stored in host LD and incorporates these lipids into its own membranes and LD. Exogenous addition of oleic acid stimulates LD biogenesis in the host cell and results in the overaccumulation of neutral lipids in very large LD inside the parasite. To access LD-derived lipids, Toxoplasma intercepts and internalizes within the PV host LD, some of which remaining associated with Rab7, which become wrapped by an intravacuolar network of membranes (IVN). Mutant parasites impaired in IVN formation display diminished capacity of lipid uptake from host LD. Moreover, parasites lacking an IVN-localized phospholipase A2 are less proficient in salvaging lipids from host LD in the PV, suggesting a major contribution of the IVN for host LD processing in the PV and, thus lipid content release. Interestingly, gavage of parasites with lipids unveils, for the first time, the presence in Toxoplasma of endocytic-like structures containing lipidic material originating from the PV lumen. This study highlights the reliance of Toxoplasma on host LD for its intracellular development and the parasite's capability in scavenging neutral lipids from host LD.

  9. Lipid Storage Diseases

    Science.gov (United States)

    ... seizures, loss of muscle tone, learning problems, spasticity, feeding and swallowing difficulties, slurred speech, hypersensitivity to ... storage diseases are a group of inherited metabolic disorders in which harmful amounts ...

  10. Bioreducible Lipid-like Nanoparticles for Intracellular Protein Delivery

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    Arellano, Carlos Luis

    Protein-based therapy is one of the most direct ways to manipulate cell function and treat human disease. Although protein therapeutics has made its way to clinical practice, with five of the top fifteen global pharmaceuticals being peptide or protein-based drugs, one common limitation is that the effects of protein therapy are only achieved through the targeting of cell surface receptors and intracellular domains. Due to the impermeability of the cell membrane to most foreign materials, entire classes of potentially therapeutic proteins cannot thoroughly be studied without a safe and efficient method of transporting proteins into the cytosol. We report the use of a combinatorially-designed bioreducible lipid-like material (termed "lipidoid") - based protein delivery platform for the transfection of human cancer cell lines. Lipidoid nanoparticles are synthesized through a thin film dispersion method. The degradation of the bioreducible nanoparticles was observed when exposed to glutathione, a highly reductive compound present in the cytosol. We demonstrate that the nanoparticles are capable of transfecting a dose-dependent concentration of our model protein, beta-galactosidase into HeLa cells. Furthermore, formulations of the lipidoid containing the cytotoxic proteins saporin and RNase-A are both capable of inhibiting tumor cell proliferation as observed in in vitro treatment of different human cancer cell lines. There was no observed loss in protein activity after lyophilization and long--term storage, indicating the potential of pre-clinical applications. Overall, we demonstrate an effective approach to protein formulation and intracellular delivery. We believe that our formulations will lead to the study of a whole class of previously untapped therapeutics that may generate new solutions for previously untreatable diseases.

  11. Erratum - Intracellular heavy metal nanoparticle storage

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    Iannitti T

    2011-01-01

    Full Text Available Iannitti T, Capone S, Gatti A, Capitani F, Cetta F, Palmieri BIntracellular heavy metal nanoparticle storage: progressive accumulation within lymph nodes with transformation from chronic inflammation to malignancy. Int J Nanomedicine. 2010;5:955–960.Dr Federico Capitani’s name was spelt incorrectly as "Frederico Capitani" in the published paper.

  12. Erratum - Intracellular heavy metal nanoparticle storage

    OpenAIRE

    Iannitti T; Capone S; Gatti A; et al

    2011-01-01

    Iannitti T, Capone S, Gatti A, Capitani F, Cetta F, Palmieri BIntracellular heavy metal nanoparticle storage: progressive accumulation within lymph nodes with transformation from chronic inflammation to malignancy. Int J Nanomedicine. 2010;5:955–960.Dr Federico Capitani’s name was spelt incorrectly as "Frederico Capitani" in the published paper.

  13. Analysis of lipid profile in lipid storage myopathy.

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    Aguennouz, M'hammed; Beccaria, Marco; Purcaro, Giorgia; Oteri, Marianna; Micalizzi, Giuseppe; Musumesci, Olimpia; Ciranni, Annmaria; Di Giorgio, Rosa Maria; Toscano, Antonio; Dugo, Paola; Mondello, Luigi

    2016-09-01

    Lipid dysmetabolism disease is a condition in which lipids are stored abnormally in organs and tissues throughout the body, causing muscle weakness (myopathy). Usually, the diagnosis of this disease and its characterization goes through dosage of Acyl CoA in plasma accompanied with evidence of droplets of intra-fibrils lipids in the patient muscle biopsy. However, to understand the pathophysiological mechanisms of lipid storage diseases, it is useful to identify the nature of lipids deposited in muscle fiber. In this work fatty acids and triglycerides profile of lipid accumulated in the muscle of people suffering from myopathies syndromes was characterized. In particular, the analyses were carried out on the muscle biopsy of people afflicted by lipid storage myopathy, such as multiple acyl-coenzyme A dehydrogenase deficiency, and neutral lipid storage disease with myopathy, and by the intramitochondrial lipid storage dysfunctions, such as deficiencies of carnitine palmitoyltransferase II enzyme. A single step extraction and derivatization procedure was applied to analyze fatty acids from muscle tissues by gas chromatography with a flame ionization detector and with an electronic impact mass spectrometer. Triglycerides, extracted by using n-hexane, were analyzed by high performance liquid chromatography coupled to mass spectrometer equipped with an atmospheric pressure chemical ionization interface. The most representative fatty acids in all samples were: C16:0 in the 13-24% range, C18:1n9 in the 20-52% range, and C18:2n6 in the 10-25% range. These fatty acids were part of the most representative triglycerides in all samples. The data obtained was statistically elaborated performing a principal component analysis. A satisfactory discrimination was obtained among the different diseases. Using component 1 vs component 3 a 43.3% of total variance was explained. Such results suggest the important role that lipid profile characterization can have in supporting a correct

  14. Lysosomal exocytosis and lipid storage disorders.

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    Samie, Mohammad Ali; Xu, Haoxing

    2014-06-01

    Lysosomes are acidic compartments in mammalian cells that are primarily responsible for the breakdown of endocytic and autophagic substrates such as membranes, proteins, and lipids into their basic building blocks. Lysosomal storage diseases (LSDs) are a group of metabolic disorders caused by genetic mutations in lysosomal hydrolases required for catabolic degradation, mutations in lysosomal membrane proteins important for catabolite export or membrane trafficking, or mutations in nonlysosomal proteins indirectly affecting these lysosomal functions. A hallmark feature of LSDs is the primary and secondary excessive accumulation of undigested lipids in the lysosome, which causes lysosomal dysfunction and cell death, and subsequently pathological symptoms in various tissues and organs. There are more than 60 types of LSDs, but an effective therapeutic strategy is still lacking for most of them. Several recent in vitro and in vivo studies suggest that induction of lysosomal exocytosis could effectively reduce the accumulation of the storage materials. Meanwhile, the molecular machinery and regulatory mechanisms for lysosomal exocytosis are beginning to be revealed. In this paper, we first discuss these recent developments with the focus on the functional interactions between lipid storage and lysosomal exocytosis. We then discuss whether lysosomal exocytosis can be manipulated to correct lysosomal and cellular dysfunction caused by excessive lipid storage, providing a potentially general therapeutic approach for LSDs. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

  15. Autophagy, lipophagy and lysosomal lipid storage disorders.

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    Ward, Carl; Martinez-Lopez, Nuria; Otten, Elsje G; Carroll, Bernadette; Maetzel, Dorothea; Singh, Rajat; Sarkar, Sovan; Korolchuk, Viktor I

    2016-04-01

    Autophagy is a catabolic process with an essential function in the maintenance of cellular and tissue homeostasis. It is primarily recognised for its role in the degradation of dysfunctional proteins and unwanted organelles, however in recent years the range of autophagy substrates has also been extended to lipids. Degradation of lipids via autophagy is termed lipophagy. The ability of autophagy to contribute to the maintenance of lipo-homeostasis becomes particularly relevant in the context of genetic lysosomal storage disorders where perturbations of autophagic flux have been suggested to contribute to the disease aetiology. Here we review recent discoveries of the molecular mechanisms mediating lipid turnover by the autophagy pathways. We further focus on the relevance of autophagy, and specifically lipophagy, to the disease mechanisms. Moreover, autophagy is also discussed as a potential therapeutic target in several key lysosomal storage disorders. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Rab32 is important for autophagy and lipid storage in Drosophila.

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    Chao Wang

    Full Text Available Lipids are essential components of all organisms. Within cells, lipids are mainly stored in a specific type of organelle, called the lipid droplet. The molecular mechanisms governing the dynamics of lipid droplets have been little explored. The protein composition of lipid droplets has been analyzed in numerous proteomic studies, and a large number of lipid droplet-associated proteins have been identified, including Rab small GTPases. Rab proteins are known to participate in many intracellular membranous events; however, their exact role in lipid droplets is largely unexplored. Here we systematically investigate the roles of Drosophila Rab family proteins in lipid storage in the larval adipose tissue, fat body. Rab32 and several other Rabs were found to affect the size of lipid droplets as well as lipid levels. Further studies showed that Rab32 and Rab32 GEF/Claret may be involved in autophagy, consequently affecting lipid storage. Loss-of-function mutants of several components in the autophagy pathway result in similar effects on lipid storage. These results highlight the potential functions of Rabs in regulating lipid metabolism.

  17. Opposed-phase MR imaging of lipid storage myopathy in a case of Chanarin-Dorfman disease

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    Gaeta, Michele; Celona, Antonio; Racchiusa, Sergio; Mazziotti, Silvio [University of Messina, Department of Radiological Sciences, Messina (Italy); Minutoli, Fabio [University of Messina, Department of Radiological Sciences, Messina (Italy); A.O.U. ' ' Policlinico G. Martino' ' , Dipartimento di Scienze Radiologiche, Messina (Italy); Toscano, Antonio; Musumeci, Olimpia [University of Messina, Department of Neurosciences, Psychiatry and Anaesthesiology, Messina (Italy)

    2008-11-15

    Chanarin-Dorfman disease (CDD) is a rare genetic disorder characterized by ichthyosis, myopathy, central nervous system disturbances, and intracellular lipid storage in muscle fibers, hepatocytes, and granulocytes. We describe skeletal muscle magnetic resonance imaging findings in a case of CDD, outlining the potential role of GE T1-weighted opposed-phase sequence (chemical shift imaging) in the evaluation of lipid storage myopathies. (orig.)

  18. Opposed-phase MR imaging of lipid storage myopathy in a case of Chanarin-Dorfman disease

    International Nuclear Information System (INIS)

    Gaeta, Michele; Celona, Antonio; Racchiusa, Sergio; Mazziotti, Silvio; Minutoli, Fabio; Toscano, Antonio; Musumeci, Olimpia

    2008-01-01

    Chanarin-Dorfman disease (CDD) is a rare genetic disorder characterized by ichthyosis, myopathy, central nervous system disturbances, and intracellular lipid storage in muscle fibers, hepatocytes, and granulocytes. We describe skeletal muscle magnetic resonance imaging findings in a case of CDD, outlining the potential role of GE T1-weighted opposed-phase sequence (chemical shift imaging) in the evaluation of lipid storage myopathies. (orig.)

  19. Maternal obesity modulates intracellular lipid turnover in the human term placenta.

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    Hirschmugl, B; Desoye, G; Catalano, P; Klymiuk, I; Scharnagl, H; Payr, S; Kitzinger, E; Schliefsteiner, C; Lang, U; Wadsack, C; Hauguel-de Mouzon, S

    2017-02-01

    Obesity before pregnancy is associated with impaired metabolic status of the mother and the offspring later in life. These adverse effects have been attributed to epigenetic changes in utero, but little is known about the role of placental metabolism and its contribution to fetal development. We examined the impact of maternal pre-pregnancy obesity on the expression of genes involved in placental lipid metabolism in lean and obese women. Seventy-three lean and obese women with healthy pregnancy were recruited at term elective cesarean delivery. Metabolic parameters were measured on maternal venous blood samples. Expression of 88 genes involved in lipid metabolism was measured in whole placenta tissue. Proteins of genes differently expressed in response to maternal obesity were quantified, correlated with maternal parameters and immunolocalized in placenta sections. Isolated primary trophoblasts were used for in vitro assays. Triglyceride (TG) content was increased in placental tissue of obese (1.10, CI 1.04-1.24 mg g -1 , Pwomen. Among target genes examined, six showed positive correlation (Pobese vs lean women. CGI-58 protein levels correlated positively with maternal insulin levels and pre-pregnancy body mass index (R=0.63, Ptreatment of cultured trophoblast cells. Pre-gravid obesity significantly modifies the expression of placental genes related to transport and storage of neutral lipids. We propose that the upregulation of CGI-58, a master regulator of TG hydrolysis, contributes to the turnover of intracellular lipids in placenta of obese women, and is tightly regulated by metabolic factors of the mother.

  20. Fulminant lipid storage myopathy due to multiple acyl-coenzyme a dehydrogenase deficiency.

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    Whitaker, Charles H; Felice, Kevin J; Silvers, David; Wu, Qian

    2015-08-01

    The lipid storage myopathies, primary carnitine deficiency, neutral lipid storage disease, and multiple acyl coenzyme A dehydrogenase deficiency (MADD), are progressive disorders that cause permanent weakness. These disorders of fatty acid metabolism and intracellular triglyceride degradation cause marked fat deposition and damage to muscle cells. We describe a rapidly progressive myopathy in a previously healthy 33-year-old woman. Over 4 months, she developed a proximal and axial myopathy associated with diffuse myalgia and dysphagia, ultimately leading to respiratory failure and death. Muscle biopsy showed massive accumulation of lipid. Plasma acylcarnitine and urine organic acid analysis was consistent with MADD. This was confirmed by molecular genetic testing, which revealed 2 pathogenic mutations in the ETFDH gene. This report illustrates a late-onset case of MADD and reviews the differential diagnosis and evaluation of patients with proximal myopathy and excessive accumulation of lipid on muscle biopsy. © 2014 Wiley Periodicals, Inc.

  1. How cholesterol interacts with proteins and lipids during its intracellular transport

    DEFF Research Database (Denmark)

    Wüstner, Daniel; Solanko, Katarzyna

    2015-01-01

    Sterols, as cholesterol in mammalian cells and ergosterol in fungi, are indispensable molecules for proper functioning and nanoscale organization of the plasma membrane. Synthesis, uptake and efflux of cholesterol are regulated by a variety of protein-lipid and protein-protein interactions. Simil...... specific protein-lipid and protein-protein interactions help overcoming the extremely low water solubility of cholesterol, thereby controlling intracellular cholesterol movement. This article is part of a Special Issue entitled: Lipid-protein interactions.......Sterols, as cholesterol in mammalian cells and ergosterol in fungi, are indispensable molecules for proper functioning and nanoscale organization of the plasma membrane. Synthesis, uptake and efflux of cholesterol are regulated by a variety of protein-lipid and protein-protein interactions....... Similarly, membrane lipids and their physico-chemical properties directly affect cholesterol partitioning and thereby contribute to the highly heterogeneous intracellular cholesterol distribution. Movement of cholesterol in cells is mediated by vesicle trafficking along the endocytic and secretory pathways...

  2. Improved cytotoxicity of paclitaxel loaded in nanosized lipid carriers by intracellular delivery

    International Nuclear Information System (INIS)

    Miao, Jing; Du, Yongzhong; Yuan, Hong; Zhang, Xingguo; Li, Qian; Rao, Yuefeng; Zhao, Mengdan; Hu, Fuqiang

    2015-01-01

    Nanosized lipid carriers (NLC) can improve the limited drug-loading (DL) capacity and drug expulsion during storage, and adjust the drug release profile of solid lipid nanoparticles (SLN). In this study, Paclitaxel (PTX)-loaded NLC were prepared by solvent diffusion method using monostearin as solid lipid and oleic acid (OA) as liquid lipid matrix. The blank NLC with different OA content (the size range was from 89.5 ± 7.4 to 160.2 ± 34.6 nm) showed smaller size than the blank SLN (the size was 272.7 ± 43.6 nm), while the PTX-loaded NLC (the size range was from 481.3 ± 29.8 to 561.7 ± 38.3 nm) showed little bigger size, higher DL capacity, and faster drug in vitro release rate comparing with SLN (the size was 437.3 ± 68.2 nm). The 50 % cellular growth inhibitions (IC 50 ) of PTX-loaded NLC with 0, 5, 10, and 20 wt % OA were 0.92 ± 0.06, 0.69 ± 0.04, 0.25 ± 0.02, and 0.12 ± 0.02 µg mL −1 , respectively, while the IC 50 of Taxol TM was 1.72 ± 0.09 µg mL −1 . For analyzing cellular drug effect, cellular uptakes of fluorescent NLC and intracellular drug concentration were investigated. As the incorporation of OA into solid lipid matrix could accelerate both the cellular uptake and the PTX delivery, loaded by NLC, the cytotoxicity of PTX could be enhanced, and further enhanced by increasing OA content in NLC

  3. Magnetic lipid nanoparticles loading doxorubicin for intracellular delivery: Preparation and characteristics

    International Nuclear Information System (INIS)

    Ying Xiaoying; Du Yongzhong; Hong Linghong; Yuan Hong; Hu Fuqiang

    2011-01-01

    Tumor intracellular delivery is an effective route for targeting chemotherapy to enhance the curative effect and minimize the side effect of a drug. In this study, the magnetic lipid nanoparticles with an uptake ability by tumor cells were prepared dispersing ferroso-ferric oxide nanoparticles in aqueous phase using oleic acid (OA) as a dispersant, and following the solvent dispersion of lipid organic solution. The obtained nanoparticles with 200 nm volume average diameter and -30 mV surface zeta potential could be completely removed by external magnetic field from aqueous solution. Using doxorubicin (DOX) as a model drug, the drug-loaded magnetic lipid nanoparticles were investigated in detail, such as the effects of OA, drug and lipid content on volume average diameter, zeta potential, drug encapsulation efficiency, drug loading, and in vitro drug release. The drug loading capacity and encapsulation efficiency were enhanced with increasing drug or lipid content, reduced with increasing OA content. The in vitro drug release could be controlled by changing drug or lipid content. Cellular uptake by MCF-7 cells experiment presented the excellent internalization ability of the prepared magnetic lipid nanoparticles. These results evidenced that the present magnetic lipid nanoparticles have potential for targeting therapy of antitumor drugs. - Research highlights: → A simple solvent diffusion method was developed to prepare magnetic lipid nanoparticles. → The doxorubicin-loaded magnetic lipid nanoparticles could be controlled by preparation recipe. → Magnetic lipid nanoparticles had internalization ability into tumor cells.

  4. Lipid Involvement in Neurodegenerative Diseases of the Motor System: Insights from Lysosomal Storage Diseases.

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    Dodge, James C

    2017-01-01

    Lysosomal storage diseases (LSDs) are a heterogeneous group of rare inherited metabolic diseases that are frequently triggered by the accumulation of lipids inside organelles of the endosomal-autophagic-lysosomal system (EALS). There is now a growing realization that disrupted lysosomal homeostasis (i.e., lysosomal cacostasis) also contributes to more common neurodegenerative disorders such as Parkinson disease (PD). Lipid deposition within the EALS may also participate in the pathogenesis of some additional neurodegenerative diseases of the motor system. Here, I will highlight the lipid abnormalities and clinical manifestations that are common to LSDs and several diseases of the motor system, including amyotrophic lateral sclerosis (ALS), atypical forms of spinal muscular atrophy, Charcot-Marie-Tooth disease (CMT), hereditary spastic paraplegia (HSP), multiple system atrophy (MSA), PD and spinocerebellar ataxia (SCA). Elucidating the underlying basis of intracellular lipid mislocalization as well as its consequences in each of these disorders will likely provide innovative targets for therapeutic research.

  5. The physiology of lipid storage and use in reptiles.

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    Price, Edwin R

    2017-08-01

    Lipid metabolism is central to understanding whole-animal energetics. Reptiles store most excess energy in lipid form, mobilise those lipids when needed to meet energetic demands, and invest lipids in eggs to provide the primary source of energy to developing embryos. Here, I review the mechanisms by which non-avian reptiles store, transport, and use lipids. Many aspects of lipid absorption, transport, and storage appear to be similar to birds, including the hepatic synthesis of lipids from glucose substrates, the transport of triglycerides in lipoproteins, and the storage of lipids in adipose tissue, although adipose tissue in non-avian reptiles is usually concentrated in abdominal fat bodies or the tail. Seasonal changes in fat stores suggest that lipid storage is primarily for reproduction in most species, rather than for maintenance during aphagic periods. The effects of fasting on plasma lipid metabolites can differ from mammals and birds due to the ability of non-avian reptiles to reduce their metabolism drastically during extended fasts. The effect of fasting on levels of plasma ketones is species specific: β-hydroxybutyrate concentration may rise or fall during fasting. I also describe the process by which the bulk of lipids are deposited into oocytes during vitellogenesis. Although this process is sometimes ascribed to vitellogenin-based transport in reptiles, the majority of lipid deposition occurs via triglycerides packaged in very-low-density lipoproteins (VLDLs), based on physiological, histological, biochemical, comparative, and genomic evidence. I also discuss the evidence for non-avian reptiles using 'yolk-targeted' VLDLs during vitellogenesis. The major physiological states - feeding, fasting, and vitellogenesis - have different effects on plasma lipid metabolites, and I discuss the possibilities and potential problems of using plasma metabolites to diagnose feeding condition in non-avian reptiles. © 2016 Cambridge Philosophical Society.

  6. Refractory Hyperlactatemia with Organ Insufficiency in Lipid Storage Myopathy.

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    Xu, Yuanda; Zhou, Li; Liang, Weibo; He, Weiqun; Liu, Xiaoqing; Liang, Xiuling; Zhong, Nanshan; Li, Yimin

    2015-08-01

    Lipid storage myopathy is a metabolic disorder characterized by abnormal lipid accumulation in muscle fibers and progressive muscle weakness. Here, we report the case of a 17-year-old woman with progressive muscle weakness, refractory hyperlactatemia, and multiple organ insufficiency. Severe pneumonia was the initial diagnosis. After anti-infective treatment, fluid resuscitation, and mechanical ventilation, the patient's symptoms improved but hyperlactatemia and muscle weakness persisted. She was empirically treated with carnitine. Biochemical tests, electromyography, and muscle biopsy confirmed lipid storage myopathy. After 7 weeks of treatment, the patient resumed normal daily life. An empirical treatment with carnitine may be beneficial for patients before an accurate diagnosis of lipid storage myopathy is made.

  7. Curcumin Mitigates the Intracellular Lipid Deposit Induced by Antipsychotics In Vitro.

    Directory of Open Access Journals (Sweden)

    Alberto Canfrán-Duque

    Full Text Available First- and second-generation antipsychotics (FGAs and SGAs, respectively, both inhibit cholesterol biosynthesis and impair the intracellular cholesterol trafficking, leading to lipid accumulation in the late endosome/lysosome compartment. In this study we examined if curcumin, a plant polyphenol that stimulates exosome release, can alleviate antipsychotic-induced intracellular lipid accumulation.HepG2 hepatocarcinoma cells were treated with antipsychotics or placebo and DiI-labelled LDL for 18 h and then exposed to curcumin for the last 2 h. Cells and media were collected separately and used for biochemical analyses, electron microscopy and immunocytochemistry. Exosomes were isolated from the incubation medium by ultracentrifugation.Curcumin treatment reduced the number of heterolysosomes and shifted their subcellular localization to the periphery, as revealed by electron microscopy, and stimulated the release of lysosomal β-hexosaminidase and exosome markers flotillin-2 and CD63 into the media. The presence of DiI in exosomes released by cells preloaded with DiI-LDL demonstrated the endolysosomal origin of the microvesicles. Furthermore, curcumin increased the secretion of cholesterol as well as LDL-derived DiI and [3H]-cholesterol, in association with a decrease of intracellular lipids. Thus, the disruption of lipid trafficking induced by FGAs or SGAs can be relieved by curcumin treatment. This polyphenol, however, did not mitigate the reduction of cholesterol esterification induced by antipsychotics.Curcumin stimulates exosome release to remove cholesterol (and presumably other lipids accumulated within the endolysosomal compartment, thereby normalizing intracellular lipid homeostasis. This action may help minimize the adverse metabolic effects of antipsychotic treatment, which should now be evaluated in clinical trials.

  8. Symptomatic lipid storage in carriers for the PNPLA2 gene.

    Science.gov (United States)

    Janssen, Mirian C H; van Engelen, Baziel; Kapusta, Livia; Lammens, Martin; van Dijk, Martin; Fischer, Judith; van der Graaf, Marinette; Wevers, Ron A; Fahrleitner, Manuela; Zimmermann, Robert; Morava, Eva

    2013-08-01

    Neutral lipid storage disease comprises a heterogeneous group of inherited disorders characterized by severe accumulation of cytoplasmic triglyceride droplets in several tissues and neutrophils. A novel type of autosomal recessive lipid myopathy due to PNPLA2 mutations was recently described with associated cardiac disease, myopathy and frequent infections, but without ichthyosis. Here we describe the clinical and biochemical characteristics of a long surviving patient and report on four carrier family members with diverse clinical involvement. Interestingly, heterozygous patients show neutral lipid storage in muscle and in the keratocytes of the skin, Jordans' bodies, mild myopathy and frequent infections. Biochemical analysis of fibroblasts obtained from patients revealed increased triglyceride storage and reduced lipid droplet-associated triglyceride hydrolase activity. Together, our data implicate that the wild-type allele cannot fully compensate for the mutated dysfunctional allele of PNPLA2 leading to triglyceride accumulation in muscle and mild myopathy in PNPLA2 mutation carriers. The presence of neutral lipid droplets in the skin in PNPLA2 mutation carriers strengthens the link between NLSD and other neutral lipid storage diseases with ichthyosis.

  9. Dorfman-Chanarin syndrome: A rare neutral lipid storage disease

    OpenAIRE

    Mitra Souvik; Samanta Moumita; Sarkar Mihir; Chatterjee Sukanta

    2010-01-01

    Dorfman-Chanarin syndrome is a rare neutral lipid storage disorder characterized by ichthyosis, lipid vacuolations in peripheral leucocytes, and multisystem involvement. It is an autosomal recessive disorder caused by mutations in the CGI-58 gene. A total of 42 cases have been reported worldwide till February 2009 out of which 4 have been previously reported from India. We report a case of a 20-month-old male with congenital ichthyosis, organomegaly, and bilateral cryptorchidism. Examination ...

  10. Cerebrotendinous xanthomatosis (a rare lipid storage disorder): a case report

    OpenAIRE

    Razi, Syed Mohd; Gupta, Abhinav Kumar; Gupta, Deepak Chand; Gutch, Manish; Gupta, Keshav Kumar; Usman, Syeda Iqra

    2016-01-01

    Background Cerebrotendinous xanthomatosis is a very rare autosomal recessive lipid storage disorder affecting bile acid biosynthesis. It is manifested by subtle neurological and non-neurological symptoms due to abnormal tissue lipid deposition. Diagnosis is usually delayed but early diagnosis and replacement therapy can prevent devastating neurological sequelae. Case presentation We present a case of a 25-year-old Asian Indian woman who presented with gait difficulty, fusiform swellings of bi...

  11. Molecular mechanism of intracellular lipid accumulation: Suppressive effect of PycnogenolR in liver cells

    Directory of Open Access Journals (Sweden)

    Shoichiro Ikuyama

    2013-09-01

    Full Text Available ABSTRACTCells are physiologically ready to accumulate lipids such as triacylglycerides in the cytoplasm.Five classes of perilipin (PLIN family proteins are known to be involved in the process of intracellular lipid accumulation. PLIN2 is expressed ubiquitously including adipocytes, hepatocytes and macrophages. Over-expression of PLIN2 is demonstrated in the lesions of fatty liver diseases and atherosclerosis. Suppression of PLIN2 expression prevents from developing these pathological conditions in animal models, suggesting that PLIN2 could be a therapeutic target molecule for excessive intracellular lipid accumulation which leads to various metabolic derangements. The PLIN2 gene promoter has two important cis-acting elements in close proximity:AP-1 element which mediates inflammatory signals and PPRE which mediates free fatty acid effect. In NMuLi mouse liver cells, FFA such as oleic acid requires both functional AP-1 and PPRE simultaneously to stimulate the promoter activity, indicating the presence of intimate interaction of inflammatory and metabolic signals on this gene. PycnogenolR, French maritime pine bark extracts, suppressed the oleic acid-induced PLIN2 expression and lipid accumulation in NMuLi cells. We found that PycnogenolR did not suppress the PLIN2 promoter activity or AP-1 binding to DNA. Instead, PycnogenolRfacilitates the PLIN2 mRNA degradation, leading to suppression of lipid accumulation. This effect seems to be independent of antioxidant effect of PycnogenolR.We raise the idea that PLIN2 is a putative target molecule for prevention of pathological condition induced by excessive lipid accumulation, and this class of natural compounds could be putative therapeutic modalities.Key words: PycnogenolR, lipid droplet, perilipin, fatty liver disease

  12. The central clock neurons regulate lipid storage in Drosophila.

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    Justin R DiAngelo

    Full Text Available A proper balance of lipid breakdown and synthesis is essential for achieving energy homeostasis as alterations in either of these processes can lead to pathological states such as obesity. The regulation of lipid metabolism is quite complex with multiple signals integrated to control overall triglyceride levels in metabolic tissues. Based upon studies demonstrating effects of the circadian clock on metabolism, we sought to determine if the central clock cells in the Drosophila brain contribute to lipid levels in the fat body, the main nutrient storage organ of the fly. Here, we show that altering the function of the Drosophila central clock neurons leads to an increase in fat body triglycerides. We also show that although triglyceride levels are not affected by age, they are increased by expression of the amyloid-beta protein in central clock neurons. The effect on lipid storage seems to be independent of circadian clock output as changes in triglycerides are not always observed in genetic manipulations that result in altered locomotor rhythms. These data demonstrate that the activity of the central clock neurons is necessary for proper lipid storage.

  13. Dorfman-Chanarin syndrome: a rare neutral lipid storage disease.

    Science.gov (United States)

    Mitra, Souvik; Samanta, Moumita; Sarkar, Mihir; Chatterjee, Sukanta

    2010-01-01

    Dorfman-Chanarin syndrome is a rare neutral lipid storage disorder characterized by ichthyosis, lipid vacuolations in peripheral leucocytes, and multisystem involvement. It is an autosomal recessive disorder caused by mutations in the CGI-58 gene. A total of 42 cases have been reported worldwide till February 2009 out of which 4 have been previously reported from India. We report a case of a 20-month-old male with congenital ichthyosis, organomegaly, and bilateral cryptorchidism. Examination of the peripheral smear revealed lipid vacuoles in the leucocytes consistent with Jordan's anomaly, which was confirmed by transmission electron microscopy. Liver biopsy revealed micronodular cirrhosis with macrovesicular steatosis while skin biopsy showed ichthyosis vulgaris. Dorfman-Chanarin syndrome was diagnosed on the basis of clinical and laboratory criteria with certain unreported manifestations. Dietary modifications were instituted and followed up after 1 year with promising results. This emphasizes the importance of neonatal screening for lipid vacuolations in peripheral blood in all cases of congenital ichthyosis.

  14. Nanomechanical mechanism for lipid bilayer damage induced by carbon nanotubes confined in intracellular vesicles.

    Science.gov (United States)

    Zhu, Wenpeng; von dem Bussche, Annette; Yi, Xin; Qiu, Yang; Wang, Zhongying; Weston, Paula; Hurt, Robert H; Kane, Agnes B; Gao, Huajian

    2016-11-01

    Understanding the behavior of low-dimensional nanomaterials confined in intracellular vesicles has been limited by the resolution of bioimaging techniques and the complex nature of the problem. Recent studies report that long, stiff carbon nanotubes are more cytotoxic than flexible varieties, but the mechanistic link between stiffness and cytotoxicity is not understood. Here we combine analytical modeling, molecular dynamics simulations, and in vitro intracellular imaging methods to reveal 1D carbon nanotube behavior within intracellular vesicles. We show that stiff nanotubes beyond a critical length are compressed by lysosomal membranes causing persistent tip contact with the inner membrane leaflet, leading to lipid extraction, lysosomal permeabilization, release of cathepsin B (a lysosomal protease) into the cytoplasm, and cell death. The precise material parameters needed to activate this unique mechanical pathway of nanomaterials interaction with intracellular vesicles were identified through coupled modeling, simulation, and experimental studies on carbon nanomaterials with wide variation in size, shape, and stiffness, leading to a generalized classification diagram for 1D nanocarbons that distinguishes pathogenic from biocompatible varieties based on a nanomechanical buckling criterion. For a wide variety of other 1D material classes (metal, oxide, polymer), this generalized classification diagram shows a critical threshold in length/width space that represents a transition from biologically soft to stiff, and thus identifies the important subset of all 1D materials with the potential to induce lysosomal permeability by the nanomechanical mechanism under investigation.

  15. LRRK2 mediated Rab8a phosphorylation promotes lipid storage.

    Science.gov (United States)

    Yu, Miao; Arshad, Muhammad; Wang, Wenmin; Zhao, Dongyu; Xu, Li; Zhou, Linkang

    2018-02-27

    Several mutations in leucine rich repeat kinase 2 (LRRK2) gene have been associated with pathogenesis of Parkinson's disease (PD), a neurodegenerative disorder marked by resting tremors, and rigidity, leading to Postural instability. It has been revealed that mutations that lead to an increase of kinase activity of LRRK2 protein are significantly associated with PD pathogenesis. Recent studies have shown that some Rab GTPases, especially Rab8, serve as substrates of LRRK2 and undergo phosphorylation in its switch II domain upon interaction. Current study was performed in order to find out the effects of the phosphorylation of Rab8 and its mutants on lipid metabolism and lipid droplets growth. The phosphorylation status of Rab8a was checked by phos-tag gel. Point mutant construct were generated to investigate the function of Rab8a. 3T3L1 cells were transfected with indicated plasmids and the lipid droplets were stained with Bodipy. Fluorescent microscopy experiments were performed to examine the sizes of lipid droplets. The interactions between Rab8a and Optineurin were determined by immunoprecipitation and western blot. Our assays demonstrated that Rab8a was phosphorylated by mutated LRRK2 that exhibits high kinase activity. Phosphorylation of Rab8a on amino acid residue T72 promoted the formation of large lipid droplets. T72D mutant of Rab8a had higher activity to promote the formation of large lipid droplets compared with wild type Rab8a, with increase in average diameter of lipid droplets from 2.10 μm to 2.46 μm. Moreover, phosphorylation of Rab8a weakened the interaction with its effector Optineurin. Y1699C mutated LRRK2 was able to phosphorylate Rab8a and phosphorylation of Rab8a on site 72 plays important role in the fusion and enlargement of lipid droplets. Taken together, our study suggests an indirect relationship between enhanced lipid storage capacity and PD pathogenesis.

  16. Breaking fat! How mycobacteria and other intracellular pathogens manipulate host lipid droplets.

    Science.gov (United States)

    Barisch, Caroline; Soldati, Thierry

    2017-10-01

    Tuberculosis (Tb) is a lung infection caused by Mycobacterium tuberculosis (Mtb). With one third of the world population latently infected, it represents the most prevalent bacterial infectious diseases worldwide. Typically, persistence is linked to so-called "dormant" slow-growing bacteria, which have a low metabolic rate and a reduced response to antibiotic treatments. However, dormant bacteria regain growth and virulence when the immune system is weakened, leading again to the active form of the disease. Fatty acids (FAs) released from host triacylglycerols (TAGs) and sterols are proposed to serve as sole carbon sources during infection. The metabolism of FAs requires beta-oxidation as well as gluconeogenesis and the glyoxylate shunt. Interestingly, the Mtb genome encodes more than hundred proteins involved in the five reactions of beta-oxidation, clearly demonstrating the importance of lipids as energy source. FAs have also been proposed to play a role during resuscitation, the resumption of replicative activities from dormancy. Lipid droplets (LDs) are energy and carbon reservoirs and have been described in all domains. TAGs and sterol esters (SEs) are stored in their hydrophobic core, surrounded by a phospholipid monolayer. Importantly, host LDs have been described as crucial for several intracellular bacterial pathogens and viruses and specifically translocate to the pathogen-containing vacuole (PVC) during mycobacteria infection. FAs released from host LDs are used by the pathogen as energy source and as building blocks for membrane synthesis. Despite their essential role, the mechanisms by which pathogenic mycobacteria induce the cellular redistribution of LDs and gain access to the stored lipids are still poorly understood. This review describes recent evidence about the dual interaction of mycobacteria with host LDs and membrane phospholipids and integrates them in a broader view of the underlying cellular processes manipulated by various intracellular

  17. Integrating lipid storage into general representations of fish energetics.

    Science.gov (United States)

    Martin, Benjamin T; Heintz, Ron; Danner, Eric M; Nisbet, Roger M

    2017-07-01

    Fish, even of the same species, can exhibit substantial variation in energy density (energy per unit wet weight). Most of this variation is due to differences in the amount of storage lipids. In addition to their importance as energy reserves for reproduction and for survival during unfavourable conditions, the accumulation of lipids represents a large energetic flux for many species, so figuring out how this energy flux is integrated with other major energy fluxes (growth, reproduction) is critical for any general theory of organismal energetics. Here, we synthesize data from a wide range of fish species and identify patterns of intraspecific variation in energy storage, and use these patterns to formulate a general model of energy allocation between growth, lipid storage and reproduction in fishes. From the compiled data we identified two patterns: (1) energy density increases with body size during the juvenile period, but is invariant with body size within the adult size range for most species, and (2) energy density changes across seasons, with depletion over winter, but increases fastest in periods of transition between favourable and unfavourable conditions for growth (i.e. fall). Based on these patterns we propose DEBlipid, a simple, general model of energy allocation that is closely related to a simplified version of Dynamic Energy Budget theory, DEBkiss. The crux of the model is that assimilated energy is partitioned, with κ fraction of energy allocated to pay maintenance costs first, and the surplus allocated to growth, and 1 - κ fraction of assimilated energy is allocated to accumulating storage lipids during the juvenile phase, and later to reproduction as adults. This mechanism, in addition to capturing the two patterns that motivated the model, was able to predict lipid dynamics in a novel context, the migration of anadromous fish from low-food freshwater to high-food marine environments. Furthermore, the model was used to explain intra and

  18. Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism

    Directory of Open Access Journals (Sweden)

    Bozza Patricia T

    1997-01-01

    Full Text Available Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositoires of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.

  19. Effect of irradiation and storage time on lipid oxidation of chilled pork

    Energy Technology Data Exchange (ETDEWEB)

    Cheng Anwei [Institute of Atomic Energy Application in Agriculture, Shandong Academy of Agricultural Science, Jinan 250100 (China); Wan Fachun [Institute of the Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Science, Jinan 250100 (China); Xu Tongcheng [Institute of Atomic Energy Application in Agriculture, Shandong Academy of Agricultural Science, Jinan 250100 (China); Du Fangling, E-mail: anweich@126.co [Institute of Atomic Energy Application in Agriculture, Shandong Academy of Agricultural Science, Jinan 250100 (China); Wang Wenliang; Zhu Qingjun [Institute of Atomic Energy Application in Agriculture, Shandong Academy of Agricultural Science, Jinan 250100 (China)

    2011-03-15

    The effects of {gamma}-irradiation with different doses (0, 2, 4, 6, 8 and 10 kGy) and storage time (0-30 days) on the lipid oxidation of chilled pork and the combined effect of irradiation and antioxidant on the lipid oxidative stability during storage at 4 {sup o}C were investigated. The results indicated that irradiation treatment increased lipid oxidation, measured as peroxide (PV) and thiobarbituric acid reactive substance (TBARS) values. Lipid oxidation was increased with the increase in storage time. The addition of tea polyphenol (TP) was effective in controlling the lipid oxidation of chilled pork after irradiation during cold storage.

  20. Dorfman-Chanarin syndrome: A rare neutral lipid storage disease

    Directory of Open Access Journals (Sweden)

    Mitra Souvik

    2010-10-01

    Full Text Available Dorfman-Chanarin syndrome is a rare neutral lipid storage disorder characterized by ichthyosis, lipid vacuolations in peripheral leucocytes, and multisystem involvement. It is an autosomal recessive disorder caused by mutations in the CGI-58 gene. A total of 42 cases have been reported worldwide till February 2009 out of which 4 have been previously reported from India. We report a case of a 20-month-old male with congenital ichthyosis, organomegaly, and bilateral cryptorchidism. Examination of the peripheral smear revealed lipid vacuoles in the leucocytes consistent with Jordan′s anomaly, which was confirmed by transmission electron microscopy. Liver biopsy revealed micronodular cirrhosis with macrovesicular steatosis while skin biopsy showed ichthyosis vulgaris. Dorfman-Chanarin syndrome was diagnosed on the basis of clinical and laboratory criteria with certain unreported manifestations. Dietary modifications were instituted and followed up after 1 year with promising results. This emphasizes the importance of neonatal screening for lipid vacuolations in peripheral blood in all cases of congenital ichthyosis.

  1. Cerebrotendinous xanthomatosis (a rare lipid storage disorder): a case report.

    Science.gov (United States)

    Razi, Syed Mohd; Gupta, Abhinav Kumar; Gupta, Deepak Chand; Gutch, Manish; Gupta, Keshav Kumar; Usman, Syeda Iqra

    2016-04-19

    Cerebrotendinous xanthomatosis is a very rare autosomal recessive lipid storage disorder affecting bile acid biosynthesis. It is manifested by subtle neurological and non-neurological symptoms due to abnormal tissue lipid deposition. Diagnosis is usually delayed but early diagnosis and replacement therapy can prevent devastating neurological sequelae. We present a case of a 25-year-old Asian Indian woman who presented with gait difficulty, fusiform swellings of bilateral tendo-Achilles and infrapatellar tendons, along with history of bilateral cataract surgery 1 year earlier. The diagnosis was made on the basis of clinical, biochemical, imaging, and histopathological analysis and replacement therapy was started. The peculiarity of the present case is the absence of any neurological manifestations which are usually the early clues to the diagnosis of cerebrotendinous xanthomatosis. The present case report emphasizes the fact that early age bilateral cataracts along with bilateral tendo-Achilles xanthomas can be early pointers toward the diagnosis of cerebrotendinous xanthomatosis.

  2. Lipids in hepatic glycogen storage diseases: pathophysiology, monitoring of dietary management and future directions.

    Science.gov (United States)

    Derks, Terry G J; van Rijn, Margreet

    2015-05-01

    Hepatic glycogen storage diseases (GSD) underscore the intimate relationship between carbohydrate and lipid metabolism. The hyperlipidemias in hepatic GSD reflect perturbed intracellular metabolism, providing biomarkers in blood to monitor dietary management. In different types of GSD, hyperlipidemias are of a different origin. Hypertriglyceridemia is most prominent in GSD type Ia and associated with long-term outcome morbidity, like pancreatitis and hepatic adenomas. In the ketotic subtypes of GSD, hypertriglyceridemia reflects the age-dependent fasting intolerance, secondary lipolysis and increased mitochondrial fatty acid oxidation. The role of high protein diets is established for ketotic types of GSD, but non-traditional dietary interventions (like medium-chain triglycerides and the ketogenic diet) in hepatic GSD are still controversial and necessitate further studies. Patients with these rare inherited disorders of carbohydrate metabolism meet several criteria of the metabolic syndrome, therefore close monitoring for cardiovascular diseases in ageing GSD patients may be justified.

  3. Triacylglycerol Storage in Lipid Droplets in Procyclic Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Stefan Allmann

    Full Text Available Carbon storage is likely to enable adaptation of trypanosomes to nutritional challenges or bottlenecks during their stage development and migration in the tsetse. Lipid droplets are candidates for this function. This report shows that feeding of T. brucei with oleate results in a 4-5 fold increase in the number of lipid droplets, as quantified by confocal fluorescence microscopy and by flow cytometry of BODIPY 493/503-stained cells. The triacylglycerol (TAG content also increased 4-5 fold, and labeled oleate is incorporated into TAG. Fatty acid carbon can thus be stored as TAG in lipid droplets under physiological growth conditions in procyclic T. brucei. β-oxidation has been suggested as a possible catabolic pathway for lipids in T. brucei. A single candidate gene, TFEα1 with coding capacity for a subunit of the trifunctional enzyme complex was identified. TFEα1 is expressed in procyclic T. brucei and present in glycosomal proteomes, Unexpectedly, a TFEα1 gene knock-out mutant still expressed wild-type levels of previously reported NADP-dependent 3-hydroxyacyl-CoA dehydrogenase activity, and therefore, another gene encodes this enzymatic activity. Homozygous Δtfeα1/Δtfeα1 null mutant cells show a normal growth rate and an unchanged glycosomal proteome in procyclic T. brucei. The decay kinetics of accumulated lipid droplets upon oleate withdrawal can be fully accounted for by the dilution effect of cell division in wild-type and Δtfeα1/Δtfeα1 cells. The absence of net catabolism of stored TAG in procyclic T. brucei, even under strictly glucose-free conditions, does not formally exclude a flux through TAG, in which biosynthesis equals catabolism. Also, the possibility remains that TAG catabolism is completely repressed by other carbon sources in culture media or developmentally activated in post-procyclic stages in the tsetse.

  4. Thermodynamics of partitioning of a series of chlorobenzenes to fish storage lipids

    Energy Technology Data Exchange (ETDEWEB)

    Wezel, A.P. van; Opperhuizen, A. [National Inst. for Coastal and Marine Management, The Hague (Netherlands)]|[Utrecht Univ. (Netherlands)

    1995-12-31

    Lipid/water partition coefficients for storage lipids from the African catfish (Clarias gariepinus) (K{sub d,sl}) were determined for a series of chlorobenzenes at three different temperatures. k{sub d,sl} values were higher than lipid/water partition coefficients for phospholipids, that were measured previously for the same compounds. Based on results of the present study and studies reported in the literature, it is concluded that fish lipids cannot be considered as a uniform compartment. The distinct properties of the various-lipids result in different lipid/water partition coefficients. The partitioning of chlorobenzenes between storage lipid and water is enthalpy-driven. The entropy of the transfer from water to lipids is unfavorable for the tested compounds. The thermodynamics of partitioning of chlorobenzenes to storage lipids is compared with literature data on the thermodynamics of partitioning to phospholipids, n-octanol and biota.

  5. Muscle MRI in neutral lipid storage disease (NLSD).

    Science.gov (United States)

    Garibaldi, Matteo; Tasca, Giorgio; Diaz-Manera, Jordi; Ottaviani, Pierfancesco; Laschena, Francesco; Pantoli, Donatella; Gerevini, Simonetta; Fiorillo, Chiara; Maggi, Lorenzo; Tasca, Elisabetta; D'Amico, Adele; Musumeci, Olimpia; Toscano, Antonio; Bruno, Claudio; Massa, Roberto; Angelini, Corrado; Bertini, Enrico; Antonini, Giovanni; Pennisi, Elena Maria

    2017-07-01

    Neutral lipid storage disease (NLSD) is a rare inherited disorder of lipid metabolism resulting in lipid droplets accumulation in different tissues. Skeletal muscle could be affected in both two different form of disease: NLSD with myopathy (NLSD-M) and NLSD with ichthyosis (NLSD-I). We present the muscle imaging data of 12 patients from the Italian Network for NLSD: ten patients presenting NLSD-M and two patients with NLSD-I. In NLSD-M gluteus minimus, semimembranosus, soleus and gastrocnemius medialis in the lower limbs and infraspinatus in the upper limbs were the most affected muscles. Gracilis, sartorius, subscapularis, pectoralis, triceps brachii and sternocleidomastoid were spared. Muscle involvement was not homogenous and characteristic "patchy" replacement was observed in at least one muscle in all the patients. Half of the patients showed one or more STIR positive muscles. In both NLSD-I cases muscle involvement was not observed by T1-TSE sequences, but one of them showed positive STIR images in more than one muscle in the leg. Our data provides evidence that muscle imaging can identify characteristic alterations in NLSD-M, characterized by a specific pattern of muscle involvement with "patchy" areas of fatty replacement. Larger cohorts are needed to assess if a distinct pattern of muscle involvement exists also for NLSD-I.

  6. Lipid storage changes in human skeletal muscle during detraining

    Directory of Open Access Journals (Sweden)

    Rong eZhu

    2015-11-01

    Full Text Available Exercise training is known to increase intramuscular triglyceride content in both trained and untrained legs. The purpose of the study was to determine the changes of intramyocellular lipids (IMCL and extramyocellular lipids (EMCL of both trained and untrained legs during detraining. We measured both IMCL and EMCL levels in previously trained versus untrained legs during 4-weeks of detraining after 6-weeks of strength training. Eight young men (aged 21.4+/- 1.4 years trained their vastus lateralis muscle in one leg using a dynamometer, whereas the contralateral leg served as untrained control. Muscle cross-sectional area (CSA, IMCL, EMCL, total creatine (creatine+phophocreatine of extensor (vastus lateralis muscles were assessed using magnetic resonance imaging (MRI and proton magnetic resonance spectra (1H-MRS before training, 3 days after and 28 days after the last bout of training. CSA was increased in both legs by Day 3 after training, and was still high at Day 28 post-training; IMCL increased in both legs by Day 3 after training, then decreased at Day 28 post-training only in the untrained leg; EMCL shows no significant change by Day 3 after training, but at Day 28 post-training has increased in the trained leg and decreased in the untrained leg; total creatine did not change significantly. Conclusion: Decreases of IMCL and EMCL storages in previously untrained leg during detraining indicates an ectopic influence on tissue lipid storage by different metabolic demand among tissues in the same human body.

  7. JCL Roundtable: enzyme replacement therapy for lipid storage disorders.

    Science.gov (United States)

    Brown, W Virgil; Desnick, Robert J; Grabowski, Gregory A

    2014-01-01

    There are several inherited disorders that involve abnormal storage of lipids in tissues leading to severe compromise of organs. Sadly, these are often accompanied by lifelong morbidity and early mortality. Disorders such as Gaucher, Fabry, and lysosomal acid lipase deficiencies (Wolman and cholesteryl ester storage diseases) have been known for many years, and provide a difficult and frustrating set of problems for patients, their families, and their physicians. With recombinant methods of protein synthesis, it is now possible to literally replace the defective enzymes that underlie the basic pathophysiology of many such disorders. The delivery of these enzymes into the affected cells is possible because of their location in the lysosomes where the natural degradation of their lipid substrates occurs. I have asked 2 well-known investigators to join us for this Roundtable. These are professors who have been involved with the research that has made this type of therapy possible and who have participated in the clinical trials that demonstrated the value of enzyme replacement therapy. They are Dr. Robert Desnick, dean of Genetic and Genomic Medicine and professor and chairman emeritus of the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai in New York City, and Dr. Gregory Grabowski, professor of Microbiology, Biochemistry, and Pediatrics, at the University of Cincinnati College of Medicine. Dr. Grabowski recently retired from that school to become the chief science officer of Synageva, a company involved in producing enzymes for this type of therapy. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  8. Evolution of the duplicated intracellular lipid-binding protein genes of teleost fishes.

    Science.gov (United States)

    Venkatachalam, Ananda B; Parmar, Manoj B; Wright, Jonathan M

    2017-08-01

    Increasing organismal complexity during the evolution of life has been attributed to the duplication of genes and entire genomes. More recently, theoretical models have been proposed that postulate the fate of duplicated genes, among them the duplication-degeneration-complementation (DDC) model. In the DDC model, the common fate of a duplicated gene is lost from the genome owing to nonfunctionalization. Duplicated genes are retained in the genome either by subfunctionalization, where the functions of the ancestral gene are sub-divided between the sister duplicate genes, or by neofunctionalization, where one of the duplicate genes acquires a new function. Both processes occur either by loss or gain of regulatory elements in the promoters of duplicated genes. Here, we review the genomic organization, evolution, and transcriptional regulation of the multigene family of intracellular lipid-binding protein (iLBP) genes from teleost fishes. Teleost fishes possess many copies of iLBP genes owing to a whole genome duplication (WGD) early in the teleost fish radiation. Moreover, the retention of duplicated iLBP genes is substantially higher than the retention of all other genes duplicated in the teleost genome. The fatty acid-binding protein genes, a subfamily of the iLBP multigene family in zebrafish, are differentially regulated by peroxisome proliferator-activated receptor (PPAR) isoforms, which may account for the retention of iLBP genes in the zebrafish genome by the process of subfunctionalization of cis-acting regulatory elements in iLBP gene promoters.

  9. Inherent lipid metabolic dysfunction in glycogen storage disease IIIa.

    Science.gov (United States)

    Li, Xin-Hua; Gong, Qi-Ming; Ling, Yun; Huang, Chong; Yu, De-Min; Gu, Lei-Lei; Liao, Xiang-Wei; Zhang, Dong-Hua; Hu, Xi-Qi; Han, Yue; Kong, Xiao-Fei; Zhang, Xin-Xin

    2014-12-05

    We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C > T (p.Gln40X) and c.753_756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients’ cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa.

  10. Refrigerated storage of platelets initiates changes in platelet surface marker expression and localization of intracellular proteins.

    Science.gov (United States)

    Wood, Ben; Padula, Matthew P; Marks, Denese C; Johnson, Lacey

    2016-10-01

    Platelets (PLTs) are currently stored at room temperature (22°C), which limits their shelf life, primarily due to the risk of bacterial growth. Alternatives to room temperature storage include PLT refrigeration (2-6°C), which inhibits bacterial growth, thus potentially allowing an extension of shelf life. Additionally, refrigerated PLTs appear more hemostatically active than conventional PLTs, which may be beneficial in certain clinical situations. However, the mechanisms responsible for this hemostatic function are not well characterized. The aim of this study was to assess the protein profile of refrigerated PLTs in an effort to understand these functional consequences. Buffy coat PLTs were pooled, split, and stored either at room temperature (20-24°C) or under refrigerated (2-6°C) conditions (n = 8 in each group). PLTs were assessed for changes in external receptor expression and actin filamentation using flow cytometry. Intracellular proteomic changes were assessed using two-dimensional gel electrophoresis and Western blotting. PLT refrigeration significantly reduced the abundance of glycoproteins (GPIb, GPIX, GPIIb, and GPIV) on the external membrane. However, refrigeration resulted in the increased expression of high-affinity integrins (αIIbβ3 and β1) and activation and apoptosis markers (CD62P, CD63, and phosphatidylserine). PLT refrigeration substantially altered the abundance and localization of several cytoskeletal proteins and resulted in an increase in actin filamentation, as measured by phalloidin staining. Refrigerated storage of PLTs induces significant changes in the expression and localization of both surface-expressed and intracellular proteins. Understanding these proteomic changes may help to identify the mechanisms resulting in the refrigeration-associated alterations in PLT function and clearance. © 2016 AABB.

  11. Intracellular lipid in papillary renal cell carcinoma (pRCC): T2 weighted (T2W) MRI and pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Schieda, Nicola; Van der Pol, Christian B.; Moosavi, Bardia; McInnes, Matthew D.F. [The Ottawa Hospital, The University of Ottawa, Department of Medical Imaging, Ottawa, Ontario (Canada); Mai, Kien T.; Flood, Trevor A. [The Ottawa Hospital, The University of Ottawa, Department of Anatomical Pathology, Ottawa, Ontario (Canada)

    2015-07-15

    To evaluate if pRCCs demonstrate intracellular lipid (i-lipid) at chemical-shift (CS) MRI, and assess T2W-MRI and pathologic characteristics. Sixty-two patients with a pRCC diagnosis underwent MRI over 11 years (IRB-approved). Two radiologists independently assessed for presence of i-lipid on CS-MRI and homogeneity on T2W-MRI. Inter-observer agreement was assessed via an intraclass correlation and results were compared using the Chi-square test. Discordant cases were reviewed to establish consensus. T2W SI-ratios (SI.tumor/SI.kidney) and CS-SI index were compared using independent t-tests and Spearman correlation. Two pathologists re-evaluated the histopathology. Nine of the 62 pRCCs (14.5 %) demonstrated i-lipid; agreement was moderate (ICC = 0.63). Pathology review depicted clear cells in four tumours and foamy histiocytes in five tumours. 25.8-35.4 % (ICC = 0.65) of tumours were homogeneous on T2W-MRI. No pRCC with i-lipid was considered homogeneous (p = 0.01-0.04). Overall, T2W SI-ratio and CS-SI index were 0.89 (±0.29) and -3.63 % (-7.27 to 11.42). pRCC with i-lipid had significantly higher T2W SI-ratio (p = 0.003). There was a correlation between the CS-SI index and T2W SI-ratio, (r = 0.44, p < 0.001). Intracellular lipid is uncommonly detected in pRCCs due to clear cell changes and foamy histiocytes. These tumours are associated with heterogeneously-increased SI in T2W-MRI. (orig.)

  12. Bright and photostable push-pull pyrene dye visualizes lipid order variation between plasma and intracellular membranes.

    Science.gov (United States)

    Niko, Yosuke; Didier, Pascal; Mely, Yves; Konishi, Gen-ichi; Klymchenko, Andrey S

    2016-01-11

    Imaging lipid organization in cell membranes requires advanced fluorescent probes. Here, we show that a recently synthesized push-pull pyrene (PA), similarly to popular probe Laurdan, changes the emission maximum as a function of lipid order, but outperforms it by spectroscopic properties. In addition to red-shifted absorption compatible with common 405 nm diode laser, PA shows higher brightness and much higher photostability than Laurdan in apolar membrane environments. Moreover, PA is compatible with two-photon excitation at wavelengths >800 nm, which was successfully used for ratiometric imaging of coexisting liquid ordered and disordered phases in giant unilamellar vesicles. Fluorescence confocal microscopy in Hela cells revealed that PA efficiently stains the plasma membrane and the intracellular membranes at >20-fold lower concentrations, as compared to Laurdan. Finally, ratiometric imaging using PA reveals variation of lipid order within different cellular compartments: plasma membranes are close to liquid ordered phase of model membranes composed of sphingomyelin and cholesterol, while intracellular membranes are much less ordered, matching well membranes composed of unsaturated phospholipids without cholesterol. These differences in the lipid order were confirmed by fluorescence lifetime imaging (FLIM) at the blue edge of PA emission band. PA probe constitutes thus a new powerful tool for biomembrane research.

  13. Bright and photostable push-pull pyrene dye visualizes lipid order variation between plasma and intracellular membranes

    Science.gov (United States)

    Niko, Yosuke; Didier, Pascal; Mely, Yves; Konishi, Gen-Ichi; Klymchenko, Andrey S.

    2016-01-01

    Imaging lipid organization in cell membranes requires advanced fluorescent probes. Here, we show that a recently synthesized push-pull pyrene (PA), similarly to popular probe Laurdan, changes the emission maximum as a function of lipid order, but outperforms it by spectroscopic properties. In addition to red-shifted absorption compatible with common 405 nm diode laser, PA shows higher brightness and much higher photostability than Laurdan in apolar membrane environments. Moreover, PA is compatible with two-photon excitation at wavelengths >800 nm, which was successfully used for ratiometric imaging of coexisting liquid ordered and disordered phases in giant unilamellar vesicles. Fluorescence confocal microscopy in Hela cells revealed that PA efficiently stains the plasma membrane and the intracellular membranes at >20-fold lower concentrations, as compared to Laurdan. Finally, ratiometric imaging using PA reveals variation of lipid order within different cellular compartments: plasma membranes are close to liquid ordered phase of model membranes composed of sphingomyelin and cholesterol, while intracellular membranes are much less ordered, matching well membranes composed of unsaturated phospholipids without cholesterol. These differences in the lipid order were confirmed by fluorescence lifetime imaging (FLIM) at the blue edge of PA emission band. PA probe constitutes thus a new powerful tool for biomembrane research.

  14. Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders.

    Science.gov (United States)

    Hebbar, Sarita; Khandelwal, Avinash; Jayashree, R; Hindle, Samantha J; Chiang, Yin Ning; Yew, Joanne Y; Sweeney, Sean T; Schwudke, Dominik

    2017-12-15

    Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations in spinster (spin) mutants, a Drosophila model of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels of ceramidase and altering these lipids in spin mutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral to spin function in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed in spin mutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes in spin mutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD. © 2017 Hebbar 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).

  15. Rational design of a culture medium for the intensification of lipid storage in Chlorella sp. Performance evaluation in air-lift bioreactor.

    Science.gov (United States)

    Giordano, Pablo C; Beccaria, Alejandro J; Goicoechea, Héctor C

    2014-04-01

    An optimal medium to culture Chlorella sp., microalgae capable of storage intracellular lipids was obtained. This culture medium consists of a saline base plus carbon-energy and nitrogen sources. Significant factors exerting influence on the culture parameters were selected. Then, by applying response surface methodology coupled to desirability function, an optimal formulation, specific for the heterotrophic growth of Chlorella sp. that allows maximizing lipid concentration was obtained. During the experimental verification, the possibility of replacing commercial glucose by hydrolysates obtained from lignocellulosic materials was evaluated. Biochemical hydrolysate of corn bran allowed obtaining important improvements in lipid concentration. Finally, the optimal formulation was evaluated in an air-lift bioreactor performing a fed-batch culture. Culturing the strain in these conditions allowed rising lipid concentrations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Blocked muscle fat oxidation during exercise in neutral lipid storage disease

    DEFF Research Database (Denmark)

    Laforêt, Pascal; Ørngreen, Mette; Preisler, Nicolai

    2012-01-01

    To determine whether impaired exercise capacity in neutral lipid storage disease with myopathy is solely caused by muscle weakness or whether a defect in energy metabolism (blocked fat oxidation) may also play a role.......To determine whether impaired exercise capacity in neutral lipid storage disease with myopathy is solely caused by muscle weakness or whether a defect in energy metabolism (blocked fat oxidation) may also play a role....

  17. Marine Lipids (Omega-3 Oil) - Stability of Oil and Enriched Products During Production and Storage

    DEFF Research Database (Denmark)

    Nielsen, Nina Skall

    2015-01-01

    is prevented both during production and storage. In complex products, lipid oxidation and antioxidant mechanisms are very complex, due to the many factors that can influence the rate and extent of lipid oxidation. In order to obtain and maintain a good quality and oxidative stability of omega-3 oil...

  18. Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts.

    Directory of Open Access Journals (Sweden)

    Lindsay Van den Bossche

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a poorly understood multifactorial pandemic disorder. One of the hallmarks of NAFLD, hepatic steatosis, is a common feature in canine congenital portosystemic shunts. The aim of this study was to gain detailed insight into the pathogenesis of steatosis in this large animal model. Hepatic lipid accumulation, gene-expression analysis and HPLC-MS of neutral lipids and phospholipids in extrahepatic (EHPSS and intrahepatic portosystemic shunts (IHPSS was compared to healthy control dogs. Liver organoids of diseased dogs and healthy control dogs were incubated with palmitic- and oleic-acid, and lipid accumulation was quantified using LD540. In histological slides of shunt livers, a 12-fold increase of lipid content was detected compared to the control dogs (EHPSS P<0.01; IHPSS P = 0.042. Involvement of lipid-related genes to steatosis in portosystemic shunting was corroborated using gene-expression profiling. Lipid analysis demonstrated different triglyceride composition and a shift towards short chain and omega-3 fatty acids in shunt versus healthy dogs, with no difference in lipid species composition between shunt types. All organoids showed a similar increase in triacylglycerols after free fatty acids enrichment. This study demonstrates that steatosis is probably secondary to canine portosystemic shunts. Unravelling the pathogenesis of this hepatic steatosis might contribute to a better understanding of steatosis in NAFLD.

  19. Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts.

    Science.gov (United States)

    Van den Bossche, Lindsay; Schoonenberg, Vivien A C; Burgener, Iwan A; Penning, Louis C; Schrall, Ingrid M; Kruitwagen, Hedwig S; van Wolferen, Monique E; Grinwis, Guy C M; Kummeling, Anne; Rothuizen, Jan; van Velzen, Jeroen F; Stathonikos, Nikolas; Molenaar, Martijn R; Helms, Bernd J; Brouwers, Jos F H M; Spee, Bart; van Steenbeek, Frank G

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a poorly understood multifactorial pandemic disorder. One of the hallmarks of NAFLD, hepatic steatosis, is a common feature in canine congenital portosystemic shunts. The aim of this study was to gain detailed insight into the pathogenesis of steatosis in this large animal model. Hepatic lipid accumulation, gene-expression analysis and HPLC-MS of neutral lipids and phospholipids in extrahepatic (EHPSS) and intrahepatic portosystemic shunts (IHPSS) was compared to healthy control dogs. Liver organoids of diseased dogs and healthy control dogs were incubated with palmitic- and oleic-acid, and lipid accumulation was quantified using LD540. In histological slides of shunt livers, a 12-fold increase of lipid content was detected compared to the control dogs (EHPSS Plipid-related genes to steatosis in portosystemic shunting was corroborated using gene-expression profiling. Lipid analysis demonstrated different triglyceride composition and a shift towards short chain and omega-3 fatty acids in shunt versus healthy dogs, with no difference in lipid species composition between shunt types. All organoids showed a similar increase in triacylglycerols after free fatty acids enrichment. This study demonstrates that steatosis is probably secondary to canine portosystemic shunts. Unravelling the pathogenesis of this hepatic steatosis might contribute to a better understanding of steatosis in NAFLD.

  20. Lipid Storage and Autophagy in Melanoma Cancer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Giampietri

    2017-06-01

    Full Text Available Cancer stem cells (CSC represent a key cellular subpopulation controlling biological features such as cancer progression in all cancer types. By using melanospheres established from human melanoma patients, we compared less differentiated melanosphere-derived CSC to differentiating melanosphere-derived cells. Increased lipid uptake was found in melanosphere-derived CSC vs. differentiating melanosphere-derived cells, paralleled by strong expression of lipogenic factors Sterol Regulatory Element-Binding Protein-1 (SREBP-1 and Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ. An inverse relation between lipid-storing phenotype and autophagy was also found, since microtubule-associated protein 1A/1B-Light Chain 3 (LC3 lipidation is reduced in melanosphere-derived CSC. To investigate upstream autophagy regulators, Phospho-AMP activated Protein Kinase (P-AMPK and Phospho-mammalian Target of Rapamycin (P-mTOR were analyzed; lower P-AMPK and higher P-mTOR expression in melanosphere-derived CSC were found, thus explaining, at least in part, their lower autophagic activity. In addition, co-localization of LC3-stained autophagosome spots and perilipin-stained lipid droplets was demonstrated mainly in differentiating melanosphere-derived cells, further supporting the role of autophagy in lipid droplets clearance. The present manuscript demonstrates an inverse relationship between lipid-storing phenotype and melanoma stem cells differentiation, providing novel indications involving autophagy in melanoma stem cells biology.

  1. An improved high-throughput Nile red fluorescence assay for estimating intracellular lipids in a variety of yeast species

    Science.gov (United States)

    Sitepu, I.R.; Ignatia, L.; Franz, A. K.; Wong, D. M.; Faulina, S.A.; Tsui, M.; Kanti, A.; Boundy-Mills, K.

    2012-01-01

    A rapid and inexpensive method for estimating lipid content of yeasts is needed for screening large numbers of yeasts samples. Nile red is a fluorescent lipophilic dye used for detection and quantification of intracellular lipid droplets in various biological system including algae, yeasts and filamentous fungi. However, a published assay for yeast is affected by variable diffusion across the cell membrane, and variation in the time required to reach maximal fluorescence emission. In this study, parameters that may influence the emission were varied to determine optimal assay conditions. An improved assay with a high-throughput capability was developed that includes the addition of dimethyl sulfoxide (DMSO) solvent to improve cell permeability, elimination of the washing step, the reduction of Nile red concentration, kinetic readings rather than single time-point reading, and utilization of a black 96-well microplate. The improved method was validated by comparison to gravimetric determination of lipid content of a broad variety of ascomycete and basidiomycete yeast species. PMID:22985718

  2. Intracellular localization of two betaine lipids by cell fractionation and immunomicroscopy.

    Science.gov (United States)

    Künzler, K; Eichenberger, W; Radunz, A

    1997-01-01

    The cellular localization of the betaine lipids diacylglyceryl-N,N,N-trimethylhomoserine (DGTS) and diacylglycerylhydroxymethyl-N,N,N-trimethyl-beta-alanine (DGTA) was investigated by a) chemical analysis of subcellular fractions and b) immunochemical methods using specific antisera and either fluorescence microscopy or electron microscopy for detection of the label. A homogenate of Lycopodium annotinum (Pteridophyta) was fractionated by differential and density gradient centrifugation. The particulate fractions obtained were analyzed for chlorophyll, cyt c oxidase, NADH-cyt c reductase and DGTS. Non-plastidial fractions were enriched in DGTS and only minor amounts of this lipid could be attributed to chloroplasts. Anti-DGTS and anti-DGTA sera were produced by immunization of rabbits. The monospecificity of the antisera was examined with cells of Chlamydomonas reinhardtii (Chlorophyceae) containing DGTS, Pavlova lutheri (Haptophyceae) containing DGTA and Ochromonas danica (Chrysophyceae) containing both DGTS and DGTA. Euglena gracilis which is free of betaine lipids, was used as a control. For the test, a FITC-coupled goat anti-rabbit antibody was used and detected by fluorescence microscopy. Thin sections of Ochromonas and Pavlova were incubated first with the anti-lipid sera and subsequently with a gold-coupled anti-rabbit serum and then examined in the electron microscope. With Ochromonas, anti-DGTS as well as anti-DGTA sera gave an accumulation of gold label in the cytoplasmic space but not in the chloroplasts. Similar results were obtained with Pavlova using anti-DGTA serum. These results describe for the first time the cytochemical localization of DGTS and DGTA strongly suggesting both these lipids to be associated mainly with non-plastidial structures.

  3. Lipid storage myopathy with clinical markers of Marfan syndrome: A rare association

    Directory of Open Access Journals (Sweden)

    Subasree Ramakrishnan

    2012-01-01

    Full Text Available Disorders of lipid metabolism can cause variable clinical presentations, often involving skeletal muscle, alone or together with other tissues. A 19-year-old boy presented with a 2-year history of muscle pain, cramps, exercise intolerance and progressive weakness of proximal lower limbs. Examination revealed skeletal markers of Marfan syndrome in the form of increased arm span compared with height, Kyphoscoliois, moderate pectus excavatum, high arched palate and wrist sign. He also had mild neck flexor weakness and proximal lower limb weakness with areflexia. Pathologic findings revealed lipid-laden fine vacuoles in the muscle fibers. Possibility of carnitine deficiency myopathy was considered and the patient was started on carnitine and Co Q. The patient made remarkable clinical improvement over the next 2 months. This case is reported for rarity of the association of clinical markers of Marfan syndrome and lipid storage myopathy and sparse literature on lipid storage myopathy in the Indian context.

  4. Imaging of Intracellular and Extracellular ROS Levels in Atherosclerotic Mouse Aortas Ex Vivo: Effects of Lipid Lowering by Diet or Atorvastatin.

    Science.gov (United States)

    Ekstrand, Matias; Gustafsson Trajkovska, Maria; Perman-Sundelin, Jeanna; Fogelstrand, Per; Adiels, Martin; Johansson, Martin; Mattsson-Hultén, Lillemor; Borén, Jan; Levin, Max

    2015-01-01

    The first objective was to investigate if intracellular and extracellular levels of reactive oxygen species (ROS) within the mouse aorta increase before or after diet-induced lesion formation. The second objective was to investigate if intracellular and extracellular ROS correlates to cell composition in atherosclerotic lesions. The third objective was to investigate if intracellular and extracellular ROS levels within established atherosclerotic lesions can be reduced by lipid lowering by diet or atorvastatin. To address our objectives, we established a new imaging technique to visualize and quantify intracellular and extracellular ROS levels within intact mouse aortas ex vivo. Using this technique, we found that intracellular, but not extracellular, ROS levels increased prior to lesion formation in mouse aortas. Both intracellular and extracellular ROS levels were increased in advanced lesions. Intracellular ROS correlated with lesion content of macrophages. Extracellular ROS correlated with lesion content of smooth muscle cells. The high levels of ROS in advanced lesions were reduced by 5 days high dose atorvastatin treatment but not by lipid lowering by diet. Atorvastatin treatment did not affect lesion inflammation (aortic arch mRNA levels of CXCL 1, ICAM-1, MCP-1, TNF-α, VCAM, IL-6, and IL-1β) or cellular composition (smooth muscle cell, macrophage, and T-cell content). Aortic levels of intracellular ROS increase prior to lesion formation and may be important in initiation of atherosclerosis. Our results suggest that within lesions, macrophages produce mainly intracellular ROS whereas smooth muscle cells produce extracellular ROS. Short term atorvastatin treatment, but not lipid lowering by diet, decreases ROS levels within established advanced lesions; this may help explain the lesion stabilizing and anti-inflammatory effects of long term statin treatment.

  5. Mitochondrial dysfunction in human skeletal muscle biopsies of lipid storage disorder.

    Science.gov (United States)

    Debashree, Bandopadhyay; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Natarajan, Archana; Christopher, Rita; Nalini, Atchayaram; Bindu, Parayil Sankaran; Gayathri, Narayanappa; Srinivas Bharath, Muchukunte Mukunda

    2018-02-09

    Mitochondria regulate the balance between lipid metabolism and storage in the skeletal muscle. Altered lipid transport, metabolism and storage influence the bioenergetics, redox status and insulin signalling, contributing to cardiac and neurological diseases. Lipid storage disorders (LSDs) are neurological disorders which entail intramuscular lipid accumulation and impaired mitochondrial bioenergetics in the skeletal muscle causing progressive myopathy with muscle weakness. However, the mitochondrial changes including molecular events associated with impaired lipid storage have not been completely understood in the human skeletal muscle. We carried out morphological and biochemical analysis of mitochondrial function in muscle biopsies of human subjects with LSDs (n = 7), compared to controls (n = 10). Routine histology, enzyme histochemistry and ultrastructural analysis indicated altered muscle cell morphology and mitochondrial structure. Protein profiling of the muscle mitochondria from LSD samples (n = 5) (vs. control, n = 5) by high-throughput mass spectrometric analysis revealed that impaired metabolic processes could contribute to mitochondrial dysfunction and ensuing myopathy in LSDs. We propose that impaired fatty acid and respiratory metabolism along with increased membrane permeability, elevated lipolysis and altered cristae entail mitochondrial dysfunction in LSDs. Some of these mechanisms were unique to LSD apart from others that were common to dystrophic and inflammatory muscle pathologies. Many differentially regulated mitochondrial proteins in LSD are linked with other human diseases, indicating that mitochondrial protection via targeted drugs could be a treatment modality in LSD and related metabolic diseases. © 2018 International Society for Neurochemistry.

  6. Effects of temperature during frozen storage on lipid deterioration of saithe (Pollachius virens) and hoki (Macruronus novaezelandiae) muscles.

    Science.gov (United States)

    Karlsdottir, Magnea G; Sveinsdottir, Kolbrun; Kristinsson, Hordur G; Villot, Dominique; Craft, Brian D; Arason, Sigurjon

    2014-08-01

    Lipid deterioration of two lean fish species, saithe (Pollachius virens) and hoki (Macruronus novaezelandiae), during frozen storage at -20 and -30°C (up to 18months) was studied. Lipid composition, lipid oxidation and hydrolysis, and sensory attributes were evaluated on both light and dark muscles of the fish species. Results showed significant lipid deterioration with extended storage time, but lower storage temperature showed significantly more preservative effects. A marked difference was observed between the composition of dark muscle of hoki and saithe. Polyunsaturated fatty acids were the predominant lipids in dark muscle of saithe, while monounsaturated fatty acids were predominant in dark muscle of hoki. Further, the hydrolytic activity differed greatly between dark muscle of hoki and saithe, with significantly lower activity observed in hoki. Present results indicate that both tertiary lipid oxidation and hydrolysis products are appropriate for assessing lipid deterioration of saithe and hoki light muscle during frozen storage. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Disturbed lipid metabolism in glycogen storage disease type 1

    NARCIS (Netherlands)

    Bandsma, RHJ; Smit, GPA; Kuipers, F

    2002-01-01

    Glycogen storage disease type 1 (GSD1) is an inborn error of metabolism caused by deficiency of glucose-6-phosphatase, the enzyme catalysing the conversion of glucose-6-phosphate (G6P) to glucose. GSD1 is associated with severe hyperlipidaemia and hepatic steatosis. The underlying mechanisms

  8. Carbon black nanoparticles promote endothelial activation and lipid accumulation in macrophages independently of intracellular ROS production

    DEFF Research Database (Denmark)

    Cao, Yi; Roursgaard, Martin; Danielsen, Pernille Høgh

    2014-01-01

    black (CB) exposure in cultured human umbilical vein endothelial cells (HUVECs), THP-1 (monocytes) and THP-1 derived macrophages (THP-1a). The proliferation of HUVECs or co-cultures of HUVECs and THP-1 cells were unaffected by CB exposure, whereas there was increased cytotoxicity, assessed by the LDH...... and WST-1 assays, especially in THP-1 and THP-1a cells. The CB exposure decreased the glutathione (GSH) content in THP-1 and THP-1a cells, whereas GSH was increased in HUVECs. The reactive oxygen species (ROS) production was increased in all cell types after CB exposure. A reduction of the intracellular...... GSH concentration by buthionine sulfoximine (BSO) pre-treatment further increased the CB-induced ROS production in THP-1 cells and HUVECs. The expression of adhesion molecules ICAM-1 and VCAM-1, but not adhesion of THP-1 to HUVECs or culture dishes, was elevated by CB exposure, whereas these effects...

  9. Lysosome lipid storage disorder in NCTR-BALB/c mice. II. Morphologic and cytochemical studies.

    OpenAIRE

    Shio, H.; Fowler, S.; Bhuvaneswaran, C.; Morris, M. D.

    1982-01-01

    Electron-microscopic and cytochemical studies were carried out on tissues of NCTR-BALB/c mice. These mice are affected with a neurovisceral genetic disorder involving excessive tissue accumulation of lipid. Distinctive polymorphic intracellular inclusions, bounded by a membrane and containing lamellated bodies, were found in many cells of liver, spleen, lung, kidney, intestine, lymph nodes, and brain. The inclusions transformed reticuloendothelial cells into massive foam cells. Acid phosphata...

  10. Mercury-Pollution Induction of Intracellular Lipid Accumulation and Lysosomal Compartment Amplification in the Benthic Foraminifer Ammonia parkinsoniana.

    Directory of Open Access Journals (Sweden)

    Fabrizio Frontalini

    Full Text Available Heavy metals such as mercury (Hg pose a significant health hazard through bioaccumulation and biomagnification. By penetrating cell membranes, heavy metal ions may lead to pathological conditions. Here we examined the responses of Ammonia parkinsoniana, a benthic foraminiferan, to different concentrations of Hg in the artificial sea water. Confocal images of untreated and treated specimens using fluorescent probes (Nile Red and Acridine Orange provided an opportunity for visualizing the intracellular lipid accumulation and acidic compartment regulation. With increased Hg over time, we observed an increased number of lipid droplets, which may have acted as a detoxifying organelle where Hg is sequestered and biologically inactivated. Further, Hg seems to promote the proliferation of lysosomes both in terms of number and dimension that, at the highest level of Hg, resulted in cell death. We report, for the first time, the presence of Hg within the foraminiferal cell: at the basal part of pores, in the organic linings of the foramen/septa, and as cytoplasmic accumulations.

  11. Effect of Cu2+ and pH on intracellular calcium content and lipid peroxidation in winter wheat roots

    Directory of Open Access Journals (Sweden)

    M. E. Riazanova

    2015-06-01

    Full Text Available The study investigates the effect of copper ions and pH of external solution on intracellular calcium homeostasis and lipid peroxidation in winter wheat roots. Experiment was carried out with winter wheat. Sterile seeds were germinated in Petri dishes on the filter paper soaked with acetic buffer (pH 4.7 and 6.2 at 20 °Cin the dark for 48 hours. Copper was added as CuSO4. It’s concentrations varied from 0 to 50 µM. The Ca2+-fluorescent dye Fluo-3/AM ester was loaded on 60 hour. Root fluorescence with Fluo-3 loading was detected using X-Cite Series 120 Q unit attached to microscope Olympus BX53 with camera Olympus DP72. Imaging of root cells was achieved after exciting with 488 nm laser and collection of emission signals above 512 nm. Preliminary analysis of the images was performed using software LabSens; brightness (fluorescence intensity analysis was carried out by means of ImageJ. Peroxidation of lipids was determined according to Kumar and Knowles method. It was found that pH of solution had effect on release of calcium from intracellular stores. Low pH provokes an increase of [Ca2+]cyt which may be reaction of roots to acidic medium. Copper induces increase in non-selective permeability of plasma membrane and leads to its faster depolarization. This probably initiates Ca-dependent depolarization channels which are responsible for the influx of calcium from apoplast into the cell. Changing of the membrane permeability may occur due to interaction between Cu2+ ions and Ca-binding sites on plasma membrane or may be due to binding of copper with sulfhydryl groups and increasing of POL. Copper may also damage lipid bilayer and change the activity of some non-selective channels and transporters. Reactive oxygen species which are formed under some types of stress factors, especially the effect of heavy metals, can be activators of Ca-channels. Cu2+ ions rise MDA content and promote the oxidative stress. Low medium pH also induces its

  12. Oxidative stability during storage of structured lipids produced from fish oil and caprylic acid

    DEFF Research Database (Denmark)

    Nielsen, Nina Skall; Xu, Xuebing; Timm Heinrich, Maike

    2004-01-01

    lipid (SFO), produced by enzymatic interesterification from the same oil and caprylic acid, was compared with the stability of FO. Oils were stored at 2degreesC for 11 wk followed by storage at 20degreesC for 6 wk. In addition, the antioxidative effect of adding the metal chelators EDTA or citric acid...

  13. [Influence of different iron compounds on lipid complex of vitamin fortified wheat flour under storage].

    Science.gov (United States)

    Vorob'eva, I S; Baĭkov, V G; Vorob'eva, V M; Shatniuk, L N

    2009-01-01

    Influence of different iron compounds at combined vitamin fortification on hygienic and biochemical properties of freshly grounded first-class wheat flour under storage was studied. It proved, that more intensive oxidative and hydrolytic processes take place in the lipid complex of the flour, fortified with ferrous sulfate heptahydrate.

  14. Effect of irradiation on lipid oxidation in eviscerated chicken carcasses during storage

    International Nuclear Information System (INIS)

    Hassan, I.M.; Hussein, M.F.; Mahmoud, A.A.; Hegazy, R.A.

    1988-01-01

    Oxidative changes induced in pectoralis major muscle of chicken after irradiation treatments with 0,6,10 and 20 KGy in both non frozen or frozen conditions during subsequent storage were investigated. Ultraviolet (UV) absorption, peroxides and thiobarbituric reactive substances increased in chicken lipids with increasing irradiation doses. These oxidative changes are greater in irradiated refrigerated (4 ± 1°C) than in irradiated frozen (-20°C) chicken lipids during storage. It was found the peroxides and TBA reactive substances do not accumulate as a stable end products of fat oxidation but reach a maximum during storage followed by gradual declining. The UV absorption provides an objective measure of chicken lipids autoxidation suitable for following the progress of autoxidation of irradiated chicken during subsequent non frozen (4 ± 1°C) or frozen (-20°C) storage. The extent of Maillard-like browning was followed in both unirradiated and irradiated samples during storage. All tested objective parameters correlated well with sensory assessment of odour particularly when irradiation dose was increased as well as in frozen samples

  15. CHANGES IN LIPIDS OF BULLFROG (Rana catesbeiana) MUSCLE DURING FROZEN STORAGE AND ITS RELATIONSHIP TO MYOFIBRILLAR PROTEINS SOLUBILITY

    OpenAIRE

    Ana Lúcia da Silva Corrêa LEMOS; Aloísio José ANTUNES

    2009-01-01

    ABSTRACT: Frozen storage of bullfrog (Rana catesbeiana) leg muscles, for a period of 182 days showed that the total lipid content remained constant. The phospholipid fraction decreased after two months of frozen storage. Free fatty acid content increased from 6,5% to 47,8%; this change was correlated to a decrease in myofibrillar proteins solubility. The lipid oxidation process was estimated through the determination of peroxide value. KEYWORDS: Bullfrog lipids; oxida...

  16. Mitofusin 2 decreases intracellular lipids in macrophages by regulating peroxisome proliferator-activated receptor-γ

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chun; Ge, Beihai [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China); He, Chao [Department of Cardiology, China Three Gorges University, Yichang 433000 (China); Zhang, Yi; Liu, Xiaowen [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China); Liu, Kejian [Department of Cardiology, The First Affiliated Hospital of Medical College, Shihezi University (China); Qian, Cuiping; Zhang, Yu; Peng, Wenzhong [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China); Guo, Xiaomei, E-mail: xmguo@tjh.tjmu.edu.cn [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China)

    2014-07-18

    Highlights: • Mfn2 decreases cellular lipid accumulation by activating cholesterol transporters. • PPARγ is involved in the Mfn2-mediated increase of cholesterol transporter expressions. • Inactivation of ERK1/2 and p38 is involved in Mfn2-induced PPARγ expression. - Abstract: Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease.

  17. Mitofusin 2 decreases intracellular lipids in macrophages by regulating peroxisome proliferator-activated receptor-γ

    International Nuclear Information System (INIS)

    Liu, Chun; Ge, Beihai; He, Chao; Zhang, Yi; Liu, Xiaowen; Liu, Kejian; Qian, Cuiping; Zhang, Yu; Peng, Wenzhong; Guo, Xiaomei

    2014-01-01

    Highlights: • Mfn2 decreases cellular lipid accumulation by activating cholesterol transporters. • PPARγ is involved in the Mfn2-mediated increase of cholesterol transporter expressions. • Inactivation of ERK1/2 and p38 is involved in Mfn2-induced PPARγ expression. - Abstract: Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease

  18. Kinetics of lipid-nanoparticle-mediated intracellular mRNA delivery and function

    Science.gov (United States)

    Zhdanov, Vladimir P.

    2017-10-01

    mRNA delivery into cells forms the basis for one of the new and promising ways to treat various diseases. Among suitable carriers, lipid nanoparticles (LNPs) with a size of about 100 nm are now often employed. Despite high current interest in this area, the understanding of the basic details of LNP-mediated mRNA delivery and function is limited. To clarify the kinetics of mRNA release from LNPs, the author uses three generic models implying (i) exponential, (ii) diffusion-controlled, and (iii) detachment-controlled kinetic regimes, respectively. Despite the distinct differences in these kinetics, the associated transient kinetics of mRNA translation to the corresponding protein and its degradation are shown to be not too sensitive to the details of the mRNA delivery by LNPs (or other nanocarriers). In addition, the author illustrates how this protein may temporarily influence the expression of one gene or a few equivalent genes. The analysis includes positive or negative regulation of the gene transcription via the attachment of the protein without or with positive or negative feedback in the gene expression. Stable, bistable, and oscillatory schemes have been scrutinized in this context.

  19. Single cell synchrotron FT-IR microspectroscopy reveals a link between neutral lipid and storage carbohydrate fluxes in S. cerevisiae.

    Directory of Open Access Journals (Sweden)

    Frédéric Jamme

    Full Text Available In most organisms, storage lipids are packaged into specialized structures called lipid droplets. These contain a core of neutral lipids surrounded by a monolayer of phospholipids, and various proteins which vary depending on the species. Hydrophobic structural proteins stabilize the interface between the lipid core and aqueous cellular environment (perilipin family of proteins, apolipoproteins, oleosins. We developed a genetic approach using heterologous expression in Saccharomyces cerevisiae of the Arabidopsis thaliana lipid droplet oleosin and caleosin proteins AtOle1 and AtClo1. These transformed yeasts overaccumulate lipid droplets, leading to a specific increase in storage lipids. The phenotype of these cells was explored using synchrotron FT-IR microspectroscopy to investigate the dynamics of lipid storage and cellular carbon fluxes reflected as changes in spectral fingerprints. Multivariate statistical analysis of the data showed a clear effect on storage carbohydrates and more specifically, a decrease in glycogen in our modified strains. These observations were confirmed by biochemical quantification of the storage carbohydrates glycogen and trehalose. Our results demonstrate that neutral lipid and storage carbohydrate fluxes are tightly connected and co-regulated.

  20. Effect of storage and processing of Brazilian flaxseed on lipid and lignan contents

    Directory of Open Access Journals (Sweden)

    Renée Leão Simbalista

    2012-06-01

    Full Text Available Flaxseed has been widely studied around the world; its incorporation into products habitually consumed by human populations has been stimulated due to its unique nutritional value. The objective of this study was to evaluate the chemical composition of Brazilian flaxseed, to analyze the stability of lipids present in whole flaxseed flour (WFF or partially defatted flaxseed flour (DFF stored under several temperatures, and to investigate the effect of bread making on a product containing flaxseed. Whole flaxseed flour presented (g.100 g-1 25.7 of insoluble fiber, 10.7 of soluble fiber, 38.9 of lipids, and 2.65 of lignan. Defatted flaxseed flour presented 65% less lipids, 36% more fiber and 56% more lignan than whole flaxseed flour. The fatty acid profile was maintained in the defatted flaxseed flour, and it presented a stable composition during storage under ambient temperature, refrigeration, and freezing. The fatty acid profile was similar in the bread containing defatted flaxseed flour after dough development, baking, and storage at room temperature or refrigerated. After baking, 89% of the lignan content was kept in bread. Results show that Brazilian flaxseed has an interesting chemical composition, and that defatted flaxseed, by-product of lipid extraction, presents a good stability to grind and storage under several temperatures. Thus, defatted flaxseed flour can be incorporated in bread, increasing its nutritional and functional value.

  1. Impairment of lipid storage by cadmium in the European eel (Anguilla anguilla)

    Energy Technology Data Exchange (ETDEWEB)

    Pierron, Fabien [UMR CNRS 5805 EPOC, Team GEMA, Universite Bordeaux 1 and CNRS, Place du Dr Peyneau, 33120 Arcachon (France); Baudrimont, Magalie [UMR CNRS 5805 EPOC, Team GEMA, Universite Bordeaux 1 and CNRS, Place du Dr Peyneau, 33120 Arcachon (France)]. E-mail: m.baudrimont@epoc.u-bordeaux1.fr; Bossy, Angelique [UMR CNRS 5805 EPOC, Team GEMA, Universite Bordeaux 1 and CNRS, Place du Dr Peyneau, 33120 Arcachon (France); Bourdineaud, Jean-Paul [UMR CNRS 5805 EPOC, Team GEMA, Universite Bordeaux 1 and CNRS, Place du Dr Peyneau, 33120 Arcachon (France); Brethes, Daniel [IBGC, UMR CNRS 5095, Universite Bordeaux 2 and CNRS, 1, rue Camille Saint Saens, 33077 Bordeaux Cedex (France); Elie, Pierre [Cemagref, Unite Ecosystemes Estuariens et Poissons Migrateurs Amphihalins, U.R. EPBX, Cemagref, 50 Avenue de Verdun, 33612 Cestas (France); Massabuau, Jean-Charles [UMR CNRS 5805 EPOC, Team GEMA, Universite Bordeaux 1 and CNRS, Place du Dr Peyneau, 33120 Arcachon (France)

    2007-03-10

    Because European silver eels (Anguilla anguilla) fast during their reproductive migration to the Sargasso Sea, the successful completion of their unusual life cycle depends on quantity of lipids stored beforehand. These lipids are mainly accumulated during the growth phase stage of the animals, called yellow eel, as triglycerides in muscle. They are then catabolized to provide sufficient energy to enable migration, gonad maturation and spawning. In the laboratory, we investigated the possible impact of cadmium on the lipid storage efficiency of yellow eels in order to evaluate the possible contribution of this pollutant to the reported decline of European eel populations. Eels were exposed to dissolved cadmium at nominal concentrations of 0 and 5 {mu}g L{sup -1} for 1 month. Cd toxicity was then examined by studying the activity and expression level of several enzymes involved in liver lipolysis and lipogenesis and by determining lipid content in muscle. Contaminated eels showed a lower body weight growth with a lower efficiency of lipid storage compared to controls. Using two complementary approaches, genetic and enzymatic, it was possible to conclude that this impairment is mainly explained by an increased utilisation of triglycerides since cadmium contamination did not trigger a reduced fatty acid synthesis. These observations suggest an increased fat consumption in presence of cadmium, which could compromise successful reproduction.

  2. CARS microscopy for the monitoring of lipid storage in C. elegans

    Science.gov (United States)

    Enejder, Annika; Brackmann, Christian; Axäng, Claes; Åkeson, Madeleine; Pilon, Marc

    2008-02-01

    After several years of proof-of-principle measurements and focus on technological development, it is timely to make full use of the capabilities of CARS microscopy within the biosciences. We have here identified an urgent biological problem, to which CARS microscopy provides unique insights and consequently may become a widely accepted experimental procedure. In order to improve present understanding of mechanisms underlying dysfunctional metabolism regulation reported for many of our most wide-spread diseases (obesity, diabetes, cardio-vascular diseases etc.), we have monitored genetic and environmental impacts on cellular lipid storage in the model organism C. elegans in vivo in a full-scale biological study. Important advantages of CARS microscopy could be demonstrated compared to present technology, i.e. fluorescence microscopy of labelled lipid stores. The fluorescence signal varies not only with the presence of lipids, but also with the systemic distribution of the fluorophore and the chemical properties of the surrounding medium. By instead probing high-density regions of CH bonds naturally occurring in the sample, the CARS process was shown to provide a consistent representation of the lipid stores. The increased accumulation of lipid stores in mutants with deficiencies in the insulin and transforming growth factor signalling pathways could hereby be visualized and quantified. Furthermore, spectral CARS microscopy measurements in the C-H bond region of 2780-2930 cm -1 provided the interesting observation that this accumulation comes with a shift in the ordering of the lipids from gel- to liquid phase. The present study illustrates that CARS microscopy has a strong potential to become an important instrument for systemic studies of lipid storage mechanisms in living organisms, providing new insights into the phenomena underlying metabolic disorders.

  3. CHANGES IN LIPIDS OF BULLFROG (Rana catesbeiana MUSCLE DURING FROZEN STORAGE AND ITS RELATIONSHIP TO MYOFIBRILLAR PROTEINS SOLUBILITY

    Directory of Open Access Journals (Sweden)

    Ana Lúcia da Silva Corrêa LEMOS

    2009-07-01

    Full Text Available

    ABSTRACT: Frozen storage of bullfrog (Rana catesbeiana leg muscles, for a period of 182 days showed that the total lipid content remained constant. The phospholipid fraction decreased after two months of frozen storage. Free fatty acid content increased from 6,5% to 47,8%; this change was correlated to a decrease in myofibrillar proteins solubility. The lipid oxidation process was estimated through the determination of peroxide value. KEYWORDS: Bullfrog lipids; oxidation; protein solubility; frozen storage.

  4. Impaired Autophagy in the Lipid-Storage Disorder Niemann-Pick Type C1 Disease

    OpenAIRE

    Sarkar, Sovan; Carroll, Bernadette; Buganim, Yosef; Maetzel, Dorothea; Ng, Alex H.M.; Cassady, John P.; Cohen, Malkiel A.; Chakraborty, Souvik; Wang, Haoyi; Spooner, Eric; Ploegh, Hidde; Gsponer, Joerg; Korolchuk, Viktor I.; Jaenisch, Rudolf

    2013-01-01

    Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity in several diseases. Whether alterations in autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective autophagy in Niemann-Pick type C1 (NPC1) disease associated with cholesterol accumulation, where the maturation of autophagosomes is impaired because of defective amphisome formation caused by failure in SNARE machinery, whereas the lysosomal prot...

  5. Metabolic crosstalk between membrane and storage lipids facilitates heat stress management in Schizosaccharomyces pombe

    Science.gov (United States)

    Péter, Mária; Glatz, Attila; Gudmann, Péter; Gombos, Imre; Török, Zsolt; Horváth, Ibolya; Vígh, László

    2017-01-01

    Cell membranes actively participate in stress sensing and signalling. Here we present the first in-depth lipidomic analysis to characterize alterations in the fission yeast Schizosaccharomyces pombe in response to mild heat stress (HS). The lipidome was assessed by a simple one-step methanolic extraction. Genetic manipulations that altered triglyceride (TG) content in the absence or presence of HS gave rise to distinct lipidomic fingerprints for S. pombe. Cells unable to produce TG demonstrated long-lasting growth arrest and enhanced signalling lipid generation. Our results reveal that metabolic crosstalk between membrane and storage lipids facilitates homeostatic maintenance of the membrane physical/chemical state that resists negative effects on cell growth and viability in response to HS. We propose a novel stress adaptation mechanism in which heat-induced TG synthesis contributes to membrane rigidization by accommodating unsaturated fatty acids of structural lipids, enabling their replacement by newly synthesized saturated fatty acids. PMID:28282432

  6. The Lipid-Droplet Proteome Reveals that Droplets Are a Protein-Storage Depot

    Energy Technology Data Exchange (ETDEWEB)

    Cermelli, Silvia; Guo, Yi; Gross, Steven P.; Welte, Michael

    2006-09-19

    Lipid droplets are ubiquitous organelles that are among the basic building blocks of eukaryotic cells. Despite central roles for cholesterol homeostasis and lipid metabolism, their function and protein composition are poorly understood. Results: We purified lipid droplets from Drosophila embryos and analyzed the associated proteins by capillary LC-MS-MS. Important functional groups include enzymes involved in lipid metabolism, signaling molecules, and proteins related to membrane trafficking. Unexpectedly, histones H2A, H2Av, and H2B were present. Using biochemistry, genetics, real-time imaging, and cell biology, we confirm that roughly 50% of certain embryonic histones are physically attached to lipid droplets, a localization conserved in other fly species. Histone association with droplets starts during oogenesis and is prominent in early embryos, but it is undetectable in later stages or in cultured cells. Histones on droplets are not irreversibly trapped; quantitation of droplet histone levels and transplantation experiments suggest that histones are transferred from droplets to nuclei as development proceeds. When this maternal store of histones is unavailable because lipid droplets are mislocalized, zygotic histone production starts prematurely. Conclusions: Because we uncover a striking proteomic similarity of Drosophila droplets to mammalian lipid droplets, Drosophila likely provides a good model for understanding droplet function in general. Our analysis also reveals a new function for these organelles; the massive nature of histone association with droplets and its developmental time-course suggest that droplets sequester maternally provided proteins until they are needed. We propose that lipid droplets can serve as transient storage depots for proteins that lack appropriate binding partners in the cell. Such sequestration may provide a general cellular strategy for handling excess proteins.

  7. A lipid storage-like disorder contributes to cognitive decline in HIV-infected subjects.

    Science.gov (United States)

    Bandaru, Veera Venkata Ratnam; Mielke, Michelle M; Sacktor, Ned; McArthur, Justin C; Grant, Igor; Letendre, Scott; Chang, Linda; Wojna, Valerie; Pardo, Carlos; Calabresi, Peter; Munsaka, Sody; Haughey, Norman J

    2013-10-22

    In this multicenter cohort study, we sought to identify prognostic and associative metabolic indicators for HIV-associated neurocognitive disorders (HAND). A quantitative lipidomic analysis was conducted on 524 longitudinal CSF samples collected from 7 different performance sites across the mainland United States, Hawaii, and Puerto Rico. Subjects included HIV-infected individuals with longitudinal clinical and cognitive testing data and cognitively normal HIV-negative healthy controls. At baseline, HIV+ subjects could be differentiated from HIV- controls by reductions in a single ceramide species and increases in multiple forms of cholesterol. Perturbations in cholesterol metabolism and ceramide were influenced by combined antiretroviral therapy (cART) use. There were no cross-sectional baseline differences in any lipid metabolite when HIV+ subjects were grouped according to cognitive status. However, a single sphingolipid metabolite and reduced levels of esterified cholesterols were prognostic indicators of incident cognitive decline. Longitudinal patterns of these disturbances in sphingolipid and sterol metabolism suggest that a progressive disorder of lipid metabolism that is similar to disorders of lipid storage may contribute to the pathogenesis of HAND. These findings suggest that HIV infection and cART are independently associated with a CNS metabolic disturbance, identify surrogate markers that are prognostic for cognitive decline, and implicate a lipid storage-like disorder in the progression of HAND.

  8. Raman Microspectroscopy of Individual Algal Cells: Sensing Unsaturation of Storage Lipids in vivo

    Directory of Open Access Journals (Sweden)

    Ladislav Nedbal

    2010-09-01

    Full Text Available Algae are becoming a strategic source of fuels, food, feedstocks, and biologically active compounds. This potential has stimulated the development of innovative analytical methods focused on these microorganisms. Algal lipids are among the most promising potential products for fuels as well as for nutrition. The crucial parameter characterizing the algal lipids is the degree of unsaturation of the constituent fatty acids quantified by the iodine value. Here we demonstrate the capacity of the spatially resolved Raman microspectroscopy to determine the effective iodine value in lipid storage bodies of individual living algal cells. The Raman spectra were collected from three selected algal species immobilized in an agarose gel. Prior to immobilization, the algae were cultivated in the stationary phase inducing an overproduction of lipids. We employed the characteristic peaks in the Raman scattering spectra at 1,656 cm−1 (cis C=C stretching mode and 1,445 cm−1 (CH2 scissoring mode as the markers defining the ratio of unsaturated-to-saturated carbon-carbon bonds of the fatty acids in the algal lipids. These spectral features were first quantified for pure fatty acids of known iodine value. The resultant calibration curve was then used to calculate the effective iodine value of storage lipids in the living algal cells from their Raman spectra. We demonstrated that the iodine value differs significantly for the three studied algal species. Our spectroscopic estimations of the iodine value were validated using GC-MS measurements and an excellent agreement was found for the Trachydiscus minutus species. A good agreement was also found with the earlier published data on Botryococcus braunii. Thus, we propose that Raman microspectroscopy can become technique of choice in the rapidly expanding field of algal biotechnology.

  9. Intracellular lipid dysregulation interferes with leukocyte function in the ovaries of meat-type hens under unrestricted feed intake.

    Science.gov (United States)

    Liu, Zu-Chen; Su, Chia-Ming; Xie, Yi-Lun; Chang, Chai-Ju; Chen, Jiang-Young; Wu, Shu-Wei; Chen, Yu-Hui; Walzem, Rosemary L; Huang, San-Yuan; Chen, Shuen-Ei

    2016-04-01

    Meat-type Red-feather country hens fed ad libitum (AD-hens) exhibit obesity-associated morbidities and a number of ovarian irregularities. Leukocyte participations in ovarian activities are unstudied in AD-hens. In contrast to feed-restricted hens (R-hens), ovulatory process of the F1 follicle appeared delayed in AD-hens in association with reduced F1 follicle progesterone content, gelatinase A (MMP-2) and collagenase-3 (MMP-13) activities coincident with elevated IL-1β and no production (Pcultures of granulosa cells with increasing numbers of leukocytes from either AD-hens or R-hens exhibited dose dependent reductions in progesterone production and increases in cell death. AD-hen leukocytes were less proapoptotic than their R counterparts (Pcultures with heterophils or monocytes in a dose-dependent manner (Pcultures than their respective counterparts (P<0.05). Both basal and LPS-induced IL-1β secretion and MMP-22 or MMP-2 activities in freshly isolated AD-hen leukocytes were reduced (P<0.05). Exposure of AD or R leukocytes to 0.5mM palmitate impaired IL-1β secretion and MMP-22 or MMP-2 activity. Inhibition of ceramide synthesis with FB1 and ROS production with n-MPG scavenging rescued MMP activity and IL-1β production in palmitate treated heterophils, but exacerbated monocyte suppression. These latter findings suggest that intracellular lipid dysregulation in leukocytes contributes to ovarian dysfunction in AD-hens. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Rapid screening for lipid storage disorders using biochemical markers Expert center data and review of the literature

    NARCIS (Netherlands)

    Voorink-Moret, M.; Goorden, S. M. I.; van Kuilenburg, A. B. P.; Wijburg, F. A.; Ghauharali-van der Vlugt, J. M. M.; Beers-Stet, F. S.; Zoetekouw, A.; Kulik, W.; Hollak, C. E. M.; Vaz, F. M.

    2018-01-01

    Background: In patients suspected of a lipid storage disorder (sphingolipidoses, lipidoses), confirmation of the diagnosis relies predominantly on the measurement of specific enzymatic activities and genetic studies. New UPLC-MS/MS methods have been developed to measure lysosphingolipids and

  11. Lipid oxidative changes in traditional dry fermented sausage Petrovská klobása during storage

    OpenAIRE

    Šojić, Branislav V.; Petrović, Ljiljana S.; Mandić, Anamarija I.; Sedej, Ivana J.; Džinić, Natalija R.; Tomović, Vladimir M.; Jokanović, Marija R.; Tasić, Tatjana A.; Škaljac, Snežana B.; Ikonić, Predrag M.

    2014-01-01

    The influence of drying and ripeninig conditions (traditional and industrial) in the production of dry fermented sausage Petrovská klobása, on fatty-acid composition and oxidative changes in lipids, during 7 months of storage, was investigated. During the storage period, the sum of unsaturated fatty acids and the content of free fatty acids were significantly higher (p

  12. Comparative Proteomic Analysis of Streptomyces lividans Wild-Type and ppk Mutant Strains Reveals the Importance of Storage Lipids for Antibiotic Biosynthesis

    Science.gov (United States)

    Le Maréchal, Pierre; Decottignies, Paulette; Marchand, Christophe H.; Degrouard, Jeril; Jaillard, Danièle; Dulermo, Thierry; Froissard, Marine; Smirnov, Aleksey; Chapuis, Violaine

    2013-01-01

    Streptomyces lividans TK24 is a strain that naturally produces antibiotics at low levels, but dramatic overproduction of antibiotics occurs upon interruption of the ppk gene. However, the role of the Ppk enzyme in relation to the regulation of antibiotic biosynthesis remains poorly understood. In order to gain a better understanding of the phenotype of the ppk mutant, the proteomes of the wild-type (wt) and ppk mutant strains, grown for 96 h on R2YE medium limited in phosphate, were analyzed. Intracellular proteins were separated on two-dimensional (2D) gels, spots were quantified, and those showing a 3-fold variation or more were identified by mass spectrometry. The expression of 12 proteins increased and that of 29 decreased in the ppk mutant strain. Our results suggested that storage lipid degradation rather than hexose catabolism was taking place in the mutant. In order to validate this hypothesis, the triacylglycerol contents of the wt and ppk mutant strains of S. lividans as well as that of Streptomyces coelicolor M145, a strain that produces antibiotics at high levels and is closely related to S. lividans, were assessed using electron microscopy and thin-layer chromatography. These studies highlighted the large difference in triacylglycerol contents of the three strains and confirmed the hypothetical link between storage lipid metabolism and antibiotic biosynthesis in Streptomyces. PMID:23872561

  13. Effects of storage time and temperature on lipid oxidation of egg powders enriched with natural antioxidants.

    Science.gov (United States)

    Matumoto-Pintro, Paula Toshimi; Murakami, Alice Eiko; Vital, Ana Carolina Pelaes; Croge, Camila; da Silva, Denise Felix; Ospina-Roja, Ivan Camilo; Guerra, Ana Flávia Quiles Garcia

    2017-08-01

    The lipid fraction of egg powder may be affected by storage conditions due to the development of oxidative rancidity caused by polyunsaturated fatty acids. This study evaluated egg powders enriched with antioxidants [tocopherol, catechin, lycopene, and butylated hydroxyanisole (BHA)] for conjugated dienes (during a 90-day period) and for malonaldehydes (during a 210-day period) at 25±2 and 4±1°C. The presence of lycopene and BHA increases the total phenolic compounds in the enriched egg powders, and BHA exhibits the most antioxidant activity, as quantified by an ABTS assay. Egg powders enriched with antioxidants do not show any reduction in conjugate diene production compared to controls, and no effect of storage temperature is observed; however, in the production of malonaldehyde, greater stability is observed at 4°C, and catechin is more effective in reducing oxidation during storage. The results show that natural antioxidants can be used in egg powder instead of synthetic compounds to reduce malonaldehyde production during storage. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Higher endogenous methionine in transgenic Arabidopsis seeds affects the composition of storage proteins and lipids.

    Science.gov (United States)

    Cohen, Hagai; Pajak, Agnieszka; Pandurangan, Sudhakar; Amir, Rachel; Marsolais, Frédéric

    2016-06-01

    Previous in vitro studies demonstrate that exogenous application of the sulfur-containing amino acid methionine into cultured soybean cotyledons and seedlings reduces the level of methionine-poor storage proteins and elevates those that are methionine-rich. However, the effect of higher endogenous methionine in seeds on the composition of storage products in vivo is not studied yet. We have recently produced transgenic Arabidopsis seeds having significantly higher levels of methionine. In the present work we used these seeds as a model system and profiled them for changes in the abundances of 12S-globulins and 2S-albumins, the two major groups of storage proteins, using 2D-gels and MALDI-MS detection. The findings suggest that higher methionine affects from a certain threshold the accumulation of several subunits of 12S-globulins and 2S-albumins, regardless of their methionine contents, resulting in higher total protein contents. The mRNA abundances of most of the genes encoding these proteins were either correlated or not correlated with the abundances of these proteins, implying that methionine may regulate storage proteins at both transcriptional and post-transcriptional levels. The elevations in total protein contents resulted in reduction of total lipids and altered the fatty acid composition. Altogether, the data provide new insights into the regulatory roles of elevated methionine levels on seed composition.

  15. Effects of water activity on the lipid oxidation and antioxidants of dried laver (porphyra) during storage in the dark.

    Science.gov (United States)

    Choe, Eunok; Oh, Soojung

    2013-08-01

    Lipid oxidation and antioxidant degradation in dried laver (Porphyra) were determined during storage at water activities (Aw ) of 0.11, 0.30, 0.51, 0.75, or 0.89 in the dark at 40 °C for 15 d. Lipid oxidation was evaluated by measuring peroxide value (POV) and conjugated dienoic acid (CDA) contents, and fatty acid composition was analyzed by gas chromatography. Contents of polyphenols, tocopherols, and porphyran were determined by spectrophotometry, HPLC, and gravimetry, respectively. The POV and CDA contents of the dried laver lipids increased during storage as Aw increased from 0.11 to 0.30, 0.51, 0.75, and 0.89, whereas the relative content of eicosapentaenoic acid was decreased; however, the contents of polyphenols, α-tocopherol, and porphyran in dried laver showed the reverse phenomena. Lipid oxidation and antioxidant degradation in dried laver sharply increased at an Aw of 0.51. Polyphenols, α-tocopherol, and porphyran contributed to reduction of lipid oxidation in dried laver. The degree of lipid oxidation of dried laver was more dependent on the concentration of α-tocopherol than that of either polyphenols or porphyran during storage in the dark. The results strongly suggest that the quality of dried laver can be improved by preserving tocopherols as much as possible while decreasing A(w) during storage. © 2013 Institute of Food Technologists®

  16. Radiological and clinical characterization of the lysosomal storage disorders: non-lipid disorders.

    Science.gov (United States)

    Parker, E I; Xing, M; Moreno-De-Luca, A; Harmouche, E; Terk, M R

    2014-01-01

    Lysosomal storage diseases (LSDs) are a large group of genetic metabolic disorders that result in the accumulation of abnormal material, such as mucopolysaccharides, glycoproteins, amino acids and lipids, within cells. Since many LSDs manifest during infancy or early childhood, with potentially devastating consequences if left untreated, timely identification is imperative to prevent irreversible damage and early death. In this review, the key imaging features of the non-lipid or extralipid LSDs are examined and correlated with salient clinical manifestations and genetic information. Disorders are stratified based on the type of excess material causing tissue or organ dysfunction, with descriptions of the mucopolysaccharidoses, mucolipidoses, alpha-mannosidosis, glycogen storage disorder II and cystinosis. In addition, similarities and differences in radiological findings between each of these LSDs are highlighted to facilitate further recognition. Given the rare and extensive nature of the LSDs, mastery of their multiple clinical and radiological traits may seem challenging. However, an understanding of the distinguishing imaging characteristics of LSDs and their clinical correlates may allow radiologists to play a key role in the early diagnosis of these progressive and potentially fatal disorders.

  17. Astaxanthin degradation and lipid oxidation of Pacific white shrimp oil: kinetics study and stability as affected by storage conditions

    Directory of Open Access Journals (Sweden)

    Sirima Takeungwongtrakul

    2016-02-01

    Full Text Available Abstract The kinetics of astaxanthin degradation and lipid oxidation in shrimp oil from hepatopancreas of Pacific white shrimp (Litopenaeus vannamei as affected by storage temperature were studied. When shrimp oil was incubated at different temperatures (4, 30, 45 and 60 °C for 16 h, the rate constants (k of astaxanthin degradation and lipid oxidation in shrimp oil increased with increasing temperatures (p < 0.05. Thus, astaxanthin degradation and lipid oxidation in shrimp oil were augmented at high temperature. When shrimp oils with different storage conditions (illumination, oxygen availability and temperature were stored for up to 40 days, astaxanthin contents in all samples decreased throughout storage (p < 0.05. All factors were able to enhance astaxanthin degradation during 40 days of storage. With increasing storage time, the progressive formation of primary and secondary oxidation products were found in all samples as evidenced by the increases in both peroxide values (PV and thiobarbituric acid reactive substances (TBARS (p < 0.05. Light, air and temperatures therefore had the marked effect on astaxanthin degradation and lipid oxidation in shrimp oils during the extended storage.

  18. Uptake and intracellular fate of cholera toxin subunit b-modified mesoporous silica nanoparticle-supported lipid bilayers (aka protocells) in motoneurons.

    Science.gov (United States)

    Gonzalez Porras, Maria A; Durfee, Paul; Giambini, Sebastian; Sieck, Gary C; Brinker, C Jeffrey; Mantilla, Carlos B

    2018-04-01

    Cholera toxin B (CTB) modified mesoporous silica nanoparticle supported lipid bilayers (CTB-protocells) are a promising, customizable approach for targeting therapeutic cargo to motoneurons. In the present study, the endocytic mechanism and intracellular fate of CTB-protocells in motoneurons were examined to provide information for the development of therapeutic application and cargo delivery. Pharmacological inhibitors elucidated CTB-protocells endocytosis to be dependent on the integrity of lipid rafts and macropinocytosis. Using immunofluorescence techniques, live confocal and transmission electron microscopy, CTB-protocells were primarily found in the cytosol, membrane lipid domains and Golgi. There was no difference in the amount of motoneuron activity dependent uptake of CTB-protocells in neuromuscular junctions, consistent with clathrin activation at the axon terminals during low frequency activity. In conclusion, CTB-protocells uptake is mediated principally by lipid rafts and macropinocytosis. Once internalized, CTB-protocells escape lysosomal degradation, and engage biological pathways that are not readily accessible by untargeted delivery methods. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Dual-layered nanogel-coated hollow lipid/polypeptide conjugate assemblies for potential pH-triggered intracellular drug release.

    Directory of Open Access Journals (Sweden)

    Wen-Hsuan Chiang

    Full Text Available To achieve effective intracellular anticancer drug delivery, the polymeric vesicles supplemented with the pH-responsive outlayered gels as a delivery system of doxorubicin (DOX were developed from self-assembly of the lipid/polypeptide adduct, distearin grafted poly(γ-glutamic acid (poly(γ-GA, followed by sequential deposition of chitosan and poly(γ-GA-co-γ-glutamyl oxysuccinimide-g-monomethoxy poly(ethylene glycol in combination with in situ covalent cross-linking on assembly surfaces. The resultant gel-caged polymeric vesicles (GCPVs showed superior performance in regulating drug release in response to the external pH change. Under typical physiological conditions (pH 7.4 and 37 °C at which the γ-GA/DOX ionic pairings remained mostly undisturbed, the dense outlayered gels of GCPVs significantly reduced the premature leakage of the uncomplexed payload. With the environmental pH being reduced from pH 7.4 to 4.7, the drug liberation was appreciably promoted by the massive disruption of the ionic γ-GA/DOX complexes along with the significant swelling of nanogel layers upon the increased protonation of chitosan chain segments. After being internalized by HeLa cells via endocytosis, GCPVs exhibited cytotoxic effect comparable to free DOX achieved by rapidly releasing the payload in intracellular acidic endosomes and lysosomes. This strongly implies the great promise of such unique GCPVs as an intracellular drug delivery carrier for potential anticancer treatment.

  20. Influence of chain length of pyrene fatty acids on their uptake and metabolism by Epstein-Barr-virus-transformed lymphoid cell lines from a patient with multisystemic lipid storage myopathy and from control subjects.

    OpenAIRE

    Radom, J; Salvayre, R; Levade, T; Douste-Blazy, L

    1990-01-01

    The uptake and intracellular metabolism of 4-(1-pyrene)butanoic acid (P4), 10-(1-pyrene)decanoic acid (P10) and 12-(1-pyrene)dodecanoic acid (P12) were investigated in cultured lymphoid cell lines from normal individuals and from a patient with multisystemic lipid storage myopathy (MLSM). The cellular uptake was shown to be dependent on the fatty-acid chain length, but no significant difference in the uptake of pyrene fatty acids was observed between MLSM and control lymphoid cells. After inc...

  1. First insight into the lipid uptake, storage and mobilization in arachnids: role of midgut diverticula and lipoproteins.

    Science.gov (United States)

    Laino, Aldana; Cunningham, Mónica L; García, Fernando; Heras, Horacio

    2009-12-01

    The importance of midgut diverticula (M-diverticula) and hemolymph lipoproteins in the lipid homeostasis of Polybetes phythagoricus was studied. Radioactivity distribution in tissues and hemolymph was analyzed either after feeding or injecting [1-(14)C]-palmitate. In both experiments, radioactivity was mostly taken up by M-diverticula that synthesized diacylglycerols, triacylglycerols and phospholipids in a ratio close to its lipid class composition. M-diverticula total lipids represent 8.08% (by wt), mostly triacylglycerols (74%) and phosphatidylcholine (13%). Major fatty acids were (in decreasing order of abundance) 18:1n-9, 18:2n-6, 16:0, 16:1n-7, 18:0, 18:3n-3. Spider hemocyanin-containing lipoprotein (VHDL) transported 83% of the circulating label at short incubation times. After 24h, VHDL and HDL-1 (comparable to insect lipophorin) were found to be involved in the lipid uptake and release from M-diverticula, HDL-2 playing a negligible role. Lipoprotein's labelled lipid changed with time, phospholipids becoming the main circulating lipid after 24h. These results indicate that arachnid M-diverticula play a central role in lipid synthesis, storage and movilization, analogous to insect fat body or crustacean midgut gland. The relative contribution of HDL-1 and VHDL to lipid dynamics indicated that, unlike insects, spider VHDL significantly contributes to the lipid exchange between M-diverticula and hemolymph.

  2. Changes in Lipid Oxidation and Fatty Acids in Altay Sheep Fat during a Long Time of Low Temperature Storage.

    Science.gov (United States)

    Li, Yu; Li, Ying Biao; Liu, Cheng Jiang

    2017-04-03

    Previously, we have shown that the fatty acid composition of Altay sheep tail fat is of reasonable value and is suitable for further development of possible commercial products. Changes in lipids of Altay sheep tail fat during 50 days of 4°C refrigerated storage were investigated. Lipid oxidation and lipolysis occurred during the storage. The pH showed a continually decreased from first day to the end of the storage (p acid-reactive substances (TBARS). The increase PV was observed in Altay sheep fat up to 24 days of storage and decreased from then to the day 30 (p acids identified by GS-MS demonstrated that saturated fatty acids increased from 43.6% to 56.3% and that polyunsaturated fatty acids and monounsaturated fatty acids decreased form 51.2% to 43.7% and from 2.4% to 2.1%, respectively. The content of the functional fatty acids except (C18:2 n-9), started to decrease after 20 days of storage. Those changes indicated that lipid oxidation occurred in Altay sheep tail fat during a long time of low temperature storage. In addition, the good correlation between PV/TBARS values and changes of individual fatty acids could be used as an indicator to monitor the changes of the unsaturated fatty acid during the development process of Altay sheep tail fat-related commercial products.

  3. Modelling the dynamics of growth, development and lipid storage in the marine copepodCalanus finmarchicus.

    Science.gov (United States)

    Jager, Tjalling; Salaberria, Iurgi; Altin, Dag; Nordtug, Trond; Hansen, Bjørn Henrik

    2017-01-01

    Mechanistic models are essential tools for interpreting and predicting the consequences of a changing environment and stressors such as pollution on the life histories of marine organisms. Here, we apply the simple and generic energy-budget model DEBkiss to the life history of the marine copepod Calanus finmarchicus . Model modifications were needed to accommodate the copepod life cycle, which deviates in several respects from most other animals (e.g., a sudden stop of growth after the final moult). We identified an acceleration of growth in the early copepodite stages, which could be linked to an increase in the specific feeding rate of the animals. Lipid storage, an essential element of C. finmarchicus biology, was successfully captured with the reproduction buffer of the DEBkiss model. The resulting model was fitted to a detailed data set from the literature and was able to explain growth, development and lipid storage from egg to adult, at different temperatures and food availabilities, within a single consistent framework. The parameterised model could subsequently be used to elucidate the energetic constraints on gonad maturation and reproduction. Interestingly, the overhead costs for egg production seem to be substantially higher than the default value applied in DEB-based studies. The current model provides a solid basis for applications in stress ecology, although our model analysis also identified several knowledge gaps. Specifically, further research is needed to cover the dynamics of diapause and gonad maturation, to explain the dependence of maximum body size on food and temperature, and to verify the predicted high costs for maturity maintenance.

  4. Effect of light, packaging condition and dark storage durations on colour and lipid oxidative stability of cooked ham.

    Science.gov (United States)

    Haile, Demewez Moges; De Smet, Stefaan; Claeys, Erik; Vossen, Els

    2013-04-01

    The colour and lipid oxidative stability of sliced cooked ham stored at 4 °C were studied in relation to dark storage duration, lighting and packaging conditions. Colour stability was monitored by instrumental colour measurement (CIE L*a*b* colour space) whereas lipid stability was measured by the determination of the 2-thiobarbituric acid reactive substances (TBARS). A significantly higher discoloration observed in products wrapped in foil and kept in light than products wrapped in foil and kept in dark. Colour loss was estimated by loss of redness (a*), a*/b*, nitrosomyoglobin, chroma (C); or increase of lightness (L*), MetMb, hue angle (H°). Colour loss was more dependent upon photochemical process than dark storage duration and packaging types. Lipid oxidation was not significantly affected by light exposure. However lipid oxidation was significantly affected by dark storage duration as noticed from better lipid stability of products stored for short duration in dark. Better colour stability was observed on products packed in MAP with less residual oxygen.

  5. Seed pretreatment with magnetic field alters the storage proteins and lipid profiles in harvested soybean seeds.

    Science.gov (United States)

    Radhakrishnan, Ramalingam

    2018-03-01

    The increase in crop productivity is an urgent need of the time to reduce scarcity of food in underdeveloped countries. Several biological, chemical and physical methods have been applied to promote crop yield. Application of magnetic field (MF) is an emerging physical method used to increase plant growth and yield. The reports on MF pretreatment-induced nutritional changes in harvested seeds are scarce. We previously identified the optimal frequency of MF to improve plant growth and yield as 1500 nT at 10.0 Hz. This study was aimed to investigate the effect of MF treatment on storage proteins and fatty acids in harvested soybean seeds. The results showed that MF triggered globulin production and suppressed prolamin production. However, lipid content in seeds increased, because MF exposure caused an elevation of several fatty acids including caprylic acid, palmitic acid, heptadecanoic acid, linoleic acid, lignoceric acid and eicosapentaenoic acid. This is the first report to reveal the seed pretreated MF on nutritional values of harvested seeds. This study suggests that MF treatment improves seed quality by regulating the metabolism of storage proteins and fatty acids.

  6. Influence of dietary lipid and protein sources on the sensory quality of organic rainbow trout (Oncorhynchus mykiss) after ice storage

    DEFF Research Database (Denmark)

    Green-Petersen, Ditte; Hyldig, Grethe; Jacobsen, Charlotte

    2014-01-01

    The influence of dietary protein and lipid sources on the quality of organic rainbow trout (Oncorhynchus mykiss) was studied. The protein and oil sources were fishmeal, fish oil, and organic vegetable protein and oils. Sensory profiling was performed during 3 to 14 days of ice storage along...

  7. Accumulation of bioactive lipids during storage of blood products is not cell but plasma derived and temperature dependent

    NARCIS (Netherlands)

    Vlaar, Alexander P. J.; Kulik, Wim; Nieuwland, Rienk; Peters, Charlotte P.; Tool, Anton T. J.; van Bruggen, Robin; Juffermans, Nicole P.; de Korte, Dirk

    2011-01-01

    Bioactive lipids (lysophosphatidylcholines [lysoPCs]) accumulating during storage of cell-containing blood products are thought to be causative in onset of transfusion-related acute lung injury through activation of neutrophils. LysoPCs are thought to be derived from cell membrane degradation

  8. Effects of high-fat feeding on ectopic fat storage and postprandial lipid metabolism in mouse offspring

    NARCIS (Netherlands)

    Ewijk, Van Petronella A.; Paglialunga, Sabina; Kooi, M.E.; Nunes, Patricia M.; Gemmink, Anne; Slenter, Jos; Kornips, Esther; Jörgensen, Johanna A.; Hoeks, Joris; Wildberger, Joachim E.; Hesselink, Matthijs K.C.; Glatz, Jan F.C.; Heerschap, Arend; Kersten, Sander; Schrauwen, Patrick; Schrauwen-Hinderling, Vera B.

    2015-01-01

    Objective Parental high-fat feeding was proposed to negatively impact metabolic health in offspring. Here, the ectopic fat storage in heart and liver in offspring was investigated, and the effects on mitochondrial function, de novo lipogenesis, and postprandial lipid metabolism were explored in

  9. Effects of high-fat feeding on ectopic fat storage and postprandial lipid metabolism in mouse offspring

    NARCIS (Netherlands)

    Ewijk, P.A. van; Paglialunga, S.; Kooi, M.E.; Nunes, P.M.; Gemmink, A.; Slenter, J.; Kornips, E.; Jorgensen, J.A.; Hoeks, J.; Wildberger, J.E.; Hesselink, M.K.; Glatz, J.F.C.; Heerschap, A.; Kersten, S.; Schrauwen, P.; Schrauwen-Hinderling, V.B.

    2015-01-01

    OBJECTIVE: Parental high-fat feeding was proposed to negatively impact metabolic health in offspring. Here, the ectopic fat storage in heart and liver in offspring was investigated, and the effects on mitochondrial function, de novo lipogenesis, and postprandial lipid metabolism were explored in

  10. Histochemical Effects of “Verita WG” on Glycogen and Lipid Storage in Common Carp (Cyprinus carpio L. Liver

    Directory of Open Access Journals (Sweden)

    Elenka Georgieva

    2013-12-01

    Full Text Available We aimed in the present work is to study the effects of fosetyl-Al and fenamidone based fungicide (“Verita WG” on glycogen storage and expression of lipid droplets in common carp (Cyprinus carpio, L. liver. Concentrations of the test chemical were 30 mg/L, 38 mg/L and 50 mg/L under laboratory conditions. We used PAS-reaction for detection of glycogen storage and Sudan III staining for detection of lipid droplets in common carp hepatocytes. Hence, we found that the amount of glycogen and the fat storage in the liver increased proportionally with the increased fungicide concentrations. We also found conglomerates of accumulated glycogen in certain hepatocytes at all used concentrations. Overall, the results demonstrated enhanced glyconeogenesis and fat accumulation in the common carp liver, exposed to the test chemical.

  11. Initial aggregate formation and soil carbon storage from lipid-extracted algae amendment

    Directory of Open Access Journals (Sweden)

    Katie Lewis

    2017-12-01

    Full Text Available Soil organic C (SOC storage results when organic matter inputs to soil exceed losses through decomposition, and is strongly influenced by organic matter effects on soil aggregation. We evaluated the initial effects of lipid-extracted algae (LEA, a byproduct of biofuel production, on soil aggregate formation and SOC storage. In situ field incubations were conducted by amending soil with (1 1.5% LEA, (2 3.0% LEA, (3 1.5% LEA + 1.5% wheat straw (WS and (4 soil plus inorganic N (140 kg ha−1 NH4NO3 and P [112 kg ha−1 Ca(H2PO42·H2O] as the control. Soil samples were collected 0, 3, 6, 9, and 12 months after treatment application at 0–5, 5–15, and 15–30 cm. Soil was separated into macroaggregate (>250 µm, microaggregate (250–53 µm, and silt and clay (<53 µm fractions by dry-sieving, and mean weight diameter was calculated. Soils and soil fractions were analyzed to determine C concentrations and associated δ13C values. Mean weight diameter 12 months after 3.0% LEA application was greater than the 1.5% LEA + 1.5% WS addition at the 5–15 cm depth. Soil amended with 1.5% LEA, 3.0% LEA or 1.5% LEA + 1.5% WS resulted in greater SOC after 12 months for all soil size fractions and depths. δ13C indicated that most LEA-C was initially associated with the silt and clay fraction, but later became more strongly associated with the macro- and microaggregate fractions after 12 months. Soil application of LEA enhanced initial aggregate formation and SOC storage by increasing aggregate MWD and macro- and microaggregate associated SOC over time. As the world population grows and resources become more limited, use of alternative energy sources, soil conservation, and environmental protection must be top research priorities. Our research emphasized all three and demonstrated that LEA can enhance soil structure and C storage.

  12. Rapid screening for lipid storage disorders using biochemical markers. Expert center data and review of the literature.

    Science.gov (United States)

    Voorink-Moret, M; Goorden, S M I; van Kuilenburg, A B P; Wijburg, F A; Ghauharali-van der Vlugt, J M M; Beers-Stet, F S; Zoetekouw, A; Kulik, W; Hollak, C E M; Vaz, F M

    2018-02-01

    In patients suspected of a lipid storage disorder (sphingolipidoses, lipidoses), confirmation of the diagnosis relies predominantly on the measurement of specific enzymatic activities and genetic studies. New UPLC-MS/MS methods have been developed to measure lysosphingolipids and oxysterols, which, combined with chitotriosidase activity may represent a rapid first tier screening for lipid storage disorders. A lysosphingolipid panel consisting of lysoglobotriaosylceramide (LysoGb3), lysohexosylceramide (LysoHexCer: both lysoglucosylceramide and lysogalactosylceramide), lysosphingomyelin (LysoSM) and its carboxylated analogue lysosphingomyelin-509 (LysoSM-509) was measured in control subjects and plasma samples of predominantly untreated patients affected with lipid storage disorders (n=74). In addition, the oxysterols cholestane-3β,5α,6β-triol and 7-ketocholesterol were measured in a subset of these patients (n=36) as well as chitotriosidase activity (n=43). A systematic review of the literature was performed to assess the usefulness of these biochemical markers. Specific elevations of metabolites, i.e. without overlap between controls and other lipid storage disorders, were found for several lysosomal storage diseases: increased LysoSM levels in acid sphingomyelinase deficiency (Niemann-Pick disease type A/B), LysoGb3 levels in males with classical phenotype Fabry disease and LysoHexCer (i.e. lysoglucosylceramide/lysogalactosylceramide) in Gaucher and Krabbe diseases. While elevated levels of LysoSM-509 and cholestane-3β,5α,6β-triol did not discriminate between Niemann Pick disease type C and acid sphingomyelinase deficiency, LysoSM-509/LysoSM ratio was specifically elevated in Niemann-Pick disease type C. In Gaucher disease type I, mild increases in several lysosphingolipids were found including LysoGb3 with levels in the range of non-classical Fabry males and females. Chitotriosidase showed specific elevations in symptomatic Gaucher disease, and was mildly

  13. Shwachman-Diamond syndrome presenting with early ichthyosis, associated dermal and epidermal intracellular lipid droplets, hypoglycemia, and later distinctive clinical SDS phenotype.

    Science.gov (United States)

    Scalais, Emmanuel; Connerotte, Anne-Catherine; Despontin, Karine; Biver, Armand; Ceuterick-de Groote, Chantal; Alders, Marielle; Kolivras, Athanassios; Hachem, Jean-Pierre; De Meirleir, Linda

    2016-07-01

    Shwachman-Diamond syndrome (SDS) is a recessive ribosomopathy, characterized by bone marrow failure and exocrine pancreatic insufficiency (ePI) often associated with neurodevelopmental and skeletal abnormalities. The aim of this report is to describe a SDS patient with early ichthyosis associated with dermal and epidermal intracellular lipid droplets (iLDs), hypoglycemia and later a distinctive clinical SDS phenotype. At 3 months of age, she had ichthyosis, growth retardation, and failure to thrive. She had not cytopenia. Ultrasonography (US) showed pancreatic diffuse high echogenicity. Subsequently fasting hypoketotic hypoglycemia occurred without permanent hepatomegaly or hyperlipidemia. Continuous gavage feeding was followed by clinical improvement including ichthyosis and hypoglycemia. After 14 months of age, she developed persistent neutropenia and ePI consistent with SDS. The ichthyotic skin biopsy, performed at 5 months of age, disclosed iLDs in all epidermal layers, in melanocytes, eccrine sweat glands, Schwann cells and dermal fibroblasts. These iLDs were reminiscent of those described in Dorfman-Chanarin syndrome (DCS) or Wolman's disease. Both LIPA and CGI-58 analysis did not revealed pathogenic mutation. By sequencing SBDS, a compound heterozygous for a previously reported gene mutation (c.258 + 2T>C) and a novel mutation (c.284T>G) were found. Defective SBDS may hypothetically interfere as in DCS, with neutral lipid metabolism and play a role in the SDS phenotype such as ichthyosis with dermal and epidermal iLDs and hypoglycemia. This interference with neutral lipid metabolism must most likely occur in the cytoplasm compartment as in DCS and not in the lysosomal compartment as in Wolman's disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Diacylglycerol Enrichment of Endoplasmic Reticulum or Lipid Droplets Recruits Perilipin 3/TIP47 during Lipid Storage and Mobilization*

    Science.gov (United States)

    Skinner, James R.; Shew, Trevor M.; Schwartz, Danielle M.; Tzekov, Anatoly; Lepus, Christin M.; Abumrad, Nada A.; Wolins, Nathan E.

    2009-01-01

    Fatty acid-induced triacylglycerol synthesis produces triacylglycerol droplets with a protein coat that includes perilipin 3/TIP47 and perilipin 4/S3-12. This study addresses the following two questions. Where do lipid droplets emerge, and how are their coat proteins recruited? We show that perilipin 3- and perilipin 4-coated lipid droplets emerge along the endoplasmic reticulum (ER). Blocking membrane trafficking with AlF4− during fatty acid-induced triacylglycerol synthesis drove perilipin 3 to the tubular ER. Forskolin, which like AlF4− activates adenylate cyclase, did not redistribute perilipin 3, but when added together with AlF4− perilipin 3 was recruited to lipid droplets rather than the ER. Thus inhibiting trafficking with AlF4− redistributed perilipin 3 differently under conditions of triacylglycerol synthesis (fatty acid addition) versus hydrolysis (forskolin) suggesting a shared acylglycerol-mediated mechanism. We tested whether diacylglycerol (DG), the immediate precursor of triacylglycerol and its first hydrolytic product, affects the distribution of perilipin 3. Stabilizing DG with the DG lipase inhibitor RHC80267 enhanced the perilipin 3 recruited to lipid droplets and raised DG levels in this fraction. Treating cells with a membrane-permeable DG recruited perilipin 3 to the ER. Stabilizing DG, by blocking its hydrolysis with RHC80267 or its acylation with triacsin C, enhanced recruitment of perilipin 3 to the ER. Expressing the ER enzyme DGAT1, which removes DG by converting it to triacylglycerol, attenuated perilipin 3 DG-induced ER recruitment. Membrane-permeable DG also drove perilipin 4 and 5 onto the ER. Together the data suggest that these lipid droplet proteins are recruited to DG-enriched membranes thereby linking lipid coat proteins to the metabolic state of the cell. PMID:19748893

  15. Impaired Autophagy in the Lipid-Storage Disorder Niemann-Pick Type C1 Disease

    Directory of Open Access Journals (Sweden)

    Sovan Sarkar

    2013-12-01

    Full Text Available Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity in several diseases. Whether alterations in autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective autophagy in Niemann-Pick type C1 (NPC1 disease associated with cholesterol accumulation, where the maturation of autophagosomes is impaired because of defective amphisome formation caused by failure in SNARE machinery, whereas the lysosomal proteolytic function remains unaffected. Expression of functional NPC1 protein rescues this defect. Inhibition of autophagy also causes cholesterol accumulation. Compromised autophagy was seen in disease-affected organs of Npc1 mutant mice. Of potential therapeutic relevance is that HP-β-cyclodextrin, which is used for cholesterol-depletion treatment, impedes autophagy, whereas stimulating autophagy restores its function independent of amphisome formation. Our data suggest that a low dose of HP-β-cyclodextrin that does not perturb autophagy, coupled with an autophagy inducer, may provide a rational treatment strategy for NPC1 disease.

  16. Impaired autophagy in the lipid-storage disorder Niemann-Pick type C1 disease.

    Science.gov (United States)

    Sarkar, Sovan; Carroll, Bernadette; Buganim, Yosef; Maetzel, Dorothea; Ng, Alex H M; Cassady, John P; Cohen, Malkiel A; Chakraborty, Souvik; Wang, Haoyi; Spooner, Eric; Ploegh, Hidde; Gsponer, Joerg; Korolchuk, Viktor I; Jaenisch, Rudolf

    2013-12-12

    Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity in several diseases. Whether alterations in autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective autophagy in Niemann-Pick type C1 (NPC1) disease associated with cholesterol accumulation, where the maturation of autophagosomes is impaired because of defective amphisome formation caused by failure in SNARE machinery, whereas the lysosomal proteolytic function remains unaffected. Expression of functional NPC1 protein rescues this defect. Inhibition of autophagy also causes cholesterol accumulation. Compromised autophagy was seen in disease-affected organs of Npc1 mutant mice. Of potential therapeutic relevance is that HP-β-cyclodextrin, which is used for cholesterol-depletion treatment, impedes autophagy, whereas stimulating autophagy restores its function independent of amphisome formation. Our data suggest that a low dose of HP-β-cyclodextrin that does not perturb autophagy, coupled with an autophagy inducer, may provide a rational treatment strategy for NPC1 disease. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Co-ordinate regulation of genes involved in storage lipid mobilization in Arabidopsis thaliana.

    Science.gov (United States)

    Rylott, E L; Hooks, M A; Graham, I A

    2001-05-01

    Molecular genetic approaches in the model plant Arabidopsis thaliana (Col0) are shedding new light on the role and control of the pathways associated with the mobilization of lipid reserves during oilseed germination and post-germinative growth. Numerous independent studies have reported on the expression of individual genes encoding enzymes from the three major pathways: beta-oxidation, the glyoxylate cycle and gluconeogenesis. However, a single comprehensive study of representative genes and enzymes from the different pathways in a single plant species has not been done. Here we present results from Arabidopsis that demonstrate the co-ordinate regulation of gene expression and enzyme activities for the acyl-CoA oxidase- and 3-ketoacyl-CoA thiolase-mediated steps of beta-oxidation, the isocitrate lyase and malate synthase steps of the glyoxylate cycle and the phosphoenolpyruvate carboxykinase step of gluconeogenesis. The mRNA abundance and enzyme activities increase to a peak at stage 2, 48 h after the onset of seed germination, and decline thereafter either to undetectable levels (for malate synthase and isocitrate lyase) or low basal levels (for the genes of beta-oxidation and gluconeogenesis). The co-ordinate induction of all these genes at the onset of germination raises the possibility that a global regulatory mechanism operates to induce the expression of genes associated with the mobilization of storage reserves during the heterotrophic growth period.

  18. Neutral lipid storage disease with myopathy: A whole-body nuclear MRI and metabolic study

    International Nuclear Information System (INIS)

    Laforet, Pascal; Stojkovic, Tanya; Wahbi, Karim; Eymard, Bruno; Bassez, Guillaume; Carlier, Pierre G.; Clement, Karine; Petit, Francois M.; Carlier, Robert-Yves

    2013-01-01

    Neutral lipid storage disease with myopathy (NLSDM) is caused by a mutation in the gene encoding adipose triglyceride lipase (ATGL), and is characterized by the presence of numerous triglyceride-containing cytoplasmic droplets in type I muscle fibers. Major clinical manifestations concern the heart and skeletal muscle, and some patients also present diabetes mellitus. We report the clinical, metabolic, and whole-body nuclear magnetic resonance imaging findings of three patients with NLSDM. Muscle MRI study was consistent with previous descriptions, and allowed to show a common pattern of fatty replacement. Muscle changes predominated in the paravertebral muscles, both compartments of legs, and posterior compartment of the thighs. A more variable distribution of muscle involvement was observed on upper limbs, with marked asymmetry in one patient, and alterations predominating on supra and infra spinatus, biceps brachialis and anterior compartment of arms. Cardiac NMR studies revealed anomalies despite normal echocardiography in two patients. Endocrine studies showed low leptin and adiponectine levels, a moderate increase in insulin levels at fasting state, and even greater increase after oral glucose tolerance test in one patient. Two patients had elevated triglycerides and low cholesterol-HDL. Based on these analyses, regular control of cardio-metabolic risks appear mandatory in the clinical follow-up of these subjects. (authors)

  19. Effect of thermal treatment and frozen storage on lipid decomposition of light and dark muscles of saithe (Pollachius virens).

    Science.gov (United States)

    Karlsdottir, Magnea G; Sveinsdottir, Kolbrun; Kristinsson, Hordur G; Villot, Dominique; Craft, Brian D; Arason, Sigurjon

    2014-12-01

    Lipid decomposition of saithe (Pollachius virens) light and dark muscles was monitored during frozen storage at -25°C of raw (up to 18 months) and cooked products. Samples were cooked after 0, 6 and 12 months raw storage then refrozen and stored at -25°C for 12 months to determine the stability of cooked-then-stored samples. Fatty acid profiles, formation of hydroperoxides (PV), thiobarbituric acid reactive substances (TBARS), fluorescence compounds (OFR) and free fatty acids (FFA) were evaluated throughout the storage for all samples. In general, results indicated that enzymatic lipolysis was the driving factor influencing the quality of saithe over raw storage and it mostly affected polyunsaturated lipids in the light muscle. Cooking, however, inhibited FFA formation and induced formation of PV and TBARS. This behavior was more evident in samples cooked after long raw storage periods. The initial quality of the raw material before cooking is therefore critical with regard to oxidative stability of cooked fish products. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Effects of garlic extract on color, lipid oxidation and oxidative breakdown products in raw ground beef during refrigerated storage

    Directory of Open Access Journals (Sweden)

    XINZHUANG ZHANG

    2016-03-01

    Full Text Available The study aims to investigate the effects of garlic extracts on color, lipid oxidation, and oxidative breakdown products in raw ground beef during refrigerated storage. The two treatments were:control group (C, with no addition and experiment group (D, 50 mg garlic extracts added to 100 g beef. Adding garlic extracts significant increased a* value (PA ≤ 0.05, and significant decreased TBARS and PV values (PA ≤ 0.05. The pH and –SH value of D group had a decreasing tendency (PA=0.0522 and an increasing tendency (PA=0.0636 respectively compared to C group. Garlic extracts protected phospholipids, fatty acids and polypeptides from oxidation. The results indicatethat garlic extracts have the antioxidant activity, helping maintain the meat color, inhibiting lipid oxidation and protein degradation of raw ground beef during refrigerated storage.

  1. RNase L controls terminal adipocyte differentiation, lipids storage and insulin sensitivity via CHOP10 mRNA regulation

    DEFF Research Database (Denmark)

    Fabre, Odile Martine Julie; Salehzada, T; Lambert, K

    2012-01-01

    Adipose tissue structure is altered during obesity, leading to deregulation of whole-body metabolism. Its function depends on its structure, in particular adipocytes number and differentiation stage. To better understand the mechanisms regulating adipogenesis, we have investigated the role...... is associated with CHOP10 mRNA and regulates its stability. CHOP10 expression is conserved in RNase L(-/-)-MEFs, maintaining preadipocyte state while impairing their terminal differentiation. RNase L(-/-)-MEFs have decreased lipids storage capacity, insulin sensitivity and glucose uptake. Expression of ectopic...... RNase L in RNase L(-/-)-MEFs triggers CHOP10 mRNA instability, allowing increased lipids storage, insulin response and glucose uptake. Similarly, downregulation of CHOP10 mRNA with CHOP10 siRNA in RNase L(-/-)-MEFs improves their differentiation in adipocyte. In vivo, aged RNase L(-)/(-) mice present...

  2. Effects of chilled storage and cryopreservation on sperm characteristics, antioxidant enzyme activities, and lipid peroxidation in Pacific cod Gadus microcephalus

    Science.gov (United States)

    Wang, Xueying; Shi, Xuehui; Liu, Yifan; Yu, Daode; Guan, Shuguang; Liu, Qinghua; Li, Jun

    2016-07-01

    The present study evaluated the effects of chilled storage and cryopreservation on sperm motion characteristics, antioxidant enzyme activities, and lipid peroxidation in the Pacific cod Gadus macrocephalus. Sperm motility and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (Gr), and lipid peroxidation (measured via malondialdehyde (MDA) content) were determined after the milt was stored at 4°C for 12 h, cryopreserved without cryoprotectant in 12% propylene glycol (PG), cryopreserved in 12% PG+0.1 mol/L trehalose, or cryopreserved in 12% PG spermatozoa but centrifuged to decant the supernatant prior to cryopreservation (only sperm cells were cryopreserved). After chilled storage or cryopreservation, the SOD, CAT and GPx activities were reduced in sperm cells and increased in seminal plasma in almost all treatments; sperm motility parameters were also decreased. However, the addition of trehalose into the cryoprotectant could significantly improve the postthaw sperm quality as revealed by the sperm average path velocity. This improvement might be attributed to the function of trehalose in scavenging reactive oxygen species. Chilled storage and cryopreservation had significant effects on sperm motion characteristics, antioxidant enzyme activities, and lipid peroxidation in the Pacific cod.

  3. Antioxidant activity of pomegranate peel extract on lipid and protein oxidation in beef meatballs during frozen storage.

    Science.gov (United States)

    Turgut, Sebahattin Serhat; Işıkçı, Fatma; Soyer, Ayla

    2017-07-01

    Antioxidant effect of pomegranate peel extract (PE) to retard lipid and protein oxidation in beef meatballs was investigated during frozen storage at -18±1°C. Concentrated and freeze dried aqueous extract of pomegranate peel was incorporated into freshly prepared meatball mix at 0.5% and 1.0% concentrations, and compared with 0.01% butylated hydroxytoluene (BHT) and control (without any antioxidant). In PE treated samples, particularly in high PE concentration, peroxide, malondialdehyde and carbonyl formation, loss of total protein solubility and sulfhydryl groups were significantly lower than control after 6months of storage. A diminution of both myofibrillar (MP) and sarcoplasmic (SP) proteins of high molecular weight was detected after 6months of the storage according to gel electrophoresis patterns. The 1.0% PE led to maintain colour intensity (C) and hue (h°) value. The results from sensory analyses revealed that PE addition to meatballs was effective on preventing rancid odour formation. Addition of both 0.5 and 1% PE in meatballs reduced lipid and protein oxidation and improved sensory scores. These results indicated that PE was effective on retarding lipid and protein oxidations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Effects of high-fat feeding on ectopic fat storage and postprandial lipid metabolism in mouse offspring.

    Science.gov (United States)

    van Ewijk, Petronella A; Paglialunga, Sabina; Kooi, M Eline; Nunes, Patricia M; Gemmink, Anne; Slenter, Jos; Kornips, Esther; Jörgensen, Johanna A; Hoeks, Joris; Wildberger, Joachim E; Hesselink, Matthijs K C; Glatz, Jan F C; Heerschap, Arend; Kersten, Sander; Schrauwen, Patrick; Schrauwen-Hinderling, Vera B

    2015-11-01

    Parental high-fat feeding was proposed to negatively impact metabolic health in offspring. Here, the ectopic fat storage in heart and liver in offspring was investigated, and the effects on mitochondrial function, de novo lipogenesis, and postprandial lipid metabolism were explored in detail. Male and female mice received either a high-fat (HF) or standard chow (LF) diet during mating, gestation and lactation. All offspring animals received the HF diet. Abdominal visceral adipose tissue tended to be higher in HF/HF mice. Cardiac lipid content was also higher in the HF/HF mice (LF/HF vs. 1.03% ± 0.08% vs. 1.33% ± 0.07% of water signal, P = 0.01). In contrast, hepatic lipid content tended to be lower in HF/HF mice compared to LF/HF mice. A severely disturbed postprandial lipid clearance was revealed in HF/HF mice by the results from the triglyceride (TG) tolerance tests (LF/HF vs. 6,753 ± 2,213 vs. 14,367 ± 1,978 mmol l(-1)  min(-1) , P = 0.01) and (13) C-fatty acid retention test (LF/HF vs. 2.73% ± 0.85% vs. 0.89% ± 0.26% retention from bolus, P = 0.04), which may underlie the lower hepatic lipid content. Here it is shown that HF diet negatively impacts postprandial TG clearance in offspring and results in an overall metabolic unfavorable phenotype and ectopic lipid deposition in the heart and in visceral storage sites. © 2015 The Obesity Society.

  5. Building Stable MMP2-Responsive Multifunctional Polymeric Micelles by an All-in-One Polymer-Lipid Conjugate for Tumor-Targeted Intracellular Drug Delivery.

    Science.gov (United States)

    Yao, Qing; Dai, Zhi; Hoon Choi, Jong; Kim, Dongin; Zhu, Lin

    2017-09-27

    In this study, we described an "all-in-one" polymer-lipid conjugate (PEG2k-ppTAT-PEG1k-PE) that could self-assemble to matrix metalloproteinase 2 (MMP2)-sensitive multifunctional micelles. The assembled micelles had several key features, including a protective long chain poly(ethylene glycol) (PEG2k) (the outer shell), an MMP2-sensitive peptide linker (pp) (the tumor-targeting middle layer), a trans-activating transcriptional activator (TAT) peptide (the cell-penetrating middle layer), and a stable PEG1k-PE micelle for drug loading (the inner core). In the absence of MMP2, the PEG2k-ppTAT-PEG1k-PE micelles were intact and showed low bioactivity due to the surface-anchored PEG2k, whereas in the presence of MMP2, the pp was cleaved, resulting in the PEG2k deshielding and exposure of the previously hidden TAT for enhanced intracellular drug delivery. Even if completely cleaved by MMP2, the remaining PEG1k-PE micelles were stable and the micelles' particle size and drug release were not significantly influenced. The paclitaxel (PTX)-loaded PEG2k-ppTAT-PEG1k-PE micelles showed significant MMP2-dependent cellular uptake, tumor penetration, and anticancer activity in various cancer cells and three-dimensional multicellular spheroids. Because of the enhanced intracellular drug accumulation, these multifunctional micelles were able to sensitize the drug-resistant cancer cells and their spheroids to PTX treatments. Furthermore, in vivo tumor uptake and retention data indicated that the PEG2k-ppTAT-PEG1k-PE micelles could dramatically increase the residence time of their payloads in the tumor.

  6. Sucrose controls storage lipid breakdown on gene expression level in germinating yellow lupine (Lupinus luteus L.) seeds.

    Science.gov (United States)

    Borek, Sławomir; Nuc, Katarzyna

    2011-10-15

    This study revealed that cytosolic aconitase (ACO, EC 4.2.1.3) and isocitrate lyase (ICL, EC 4.1.3.1, marker of the glyoxylate cycle) are active in germinating protein seeds of yellow lupine. The glyoxylate cycle seems to function not only in the storage tissues of food-storage organs, but also in embryonic tissue of growing embryo axes. Sucrose (60mM) added to the medium of in vitro culture of embryo axes and cotyledons decreased activity of lipase (LIP, EC 3.1.1.3) and activity of glutamate dehydrogenase (NADH-GDH, EC 1.4.1.2). The opposite effect was caused by sucrose on activity of cytosolic ACO, ICL as well as NADP(+)-dependent (EC 1.1.1.42) and NAD(+)-dependent (EC 1.1.1.41) isocitrate dehydrogenase (NADP-IDH and NAD-IDH, respectively); activity of these enzymes was clearly stimulated by sucrose. Changes in the activity of LIP, ACO, NADP-IDH, and NAD-IDH caused by sucrose were based on modifications in gene expression because corresponding changes in the enzyme activities and in the mRNA levels were observed. The significance of cytosolic ACO and NADP-IDH in carbon flow from storage lipid to amino acids, as well as the peculiar features of storage lipid breakdown during germination of lupine seeds are discussed. Copyright © 2011 Elsevier GmbH. All rights reserved.

  7. Lipid oxidative changes in traditional dry fermented sausage Petrovská klobása during storage

    Directory of Open Access Journals (Sweden)

    Šojić Branislav V.

    2014-01-01

    Full Text Available The influence of drying and ripeninig conditions (traditional and industrial in the production of dry fermented sausage Petrovská klobása, on fatty-acid composition and oxidative changes in lipids, during 7 months of storage, was investigated. During the storage period, the sum of unsaturated fatty acids and the content of free fatty acids were significantly higher (p<0.05, while the content of malondialdehyde was significantly lower in the sausage subjected to traditional conditions of drying and ripening. At the end of the storage period, contents of pentanal and hexanal in the sausage subjected to traditional conditions of drying and ripening (4.03 μg/g and 1.67 μg/g, respectively were significantly lower (p<0.05 in comparison with these contents in the sausage subjected to industrial conditions of drying and ripening. Traditional conditions of drying and ripening at lower temperatures have led to lower oxidative changes in lipids in traditional dry fermented sausage Petrovská klobása during storage period. [Projekat Ministarstva nauke Republike Srbije, br. TR31032

  8. Evaluation of pH-responsive liposomes containing amino acid-based zwitterionic lipids for improving intracellular drug delivery in vitro and in vivo.

    Science.gov (United States)

    Obata, Yosuke; Tajima, Shoji; Takeoka, Shinji

    2010-03-03

    We developed pH-responsive liposomes containing synthetic glutamic acid-based zwitterionic lipids and evaluated their properties both in vitro and in vivo with the aim of constructing an efficient liposome-based systemic drug delivery system. The glutamic acid-based lipids; 1,5-dihexadecyl N-glutamyl-L-glutamate (L1) and 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (L2) were synthesized as a pH-responsive component of liposomes that respond to endosomal pH. The zeta potential of liposomes containing L1 or L2 was positive when the solution pH was below 4.6 or 5.6, respectively, but negative at higher pH values. The pH-responsive liposomes showed improved fusogenic potential to an endosome-mimicking anionic membrane at acidic pH, where the zeta potential of the liposomes was positive. We then prepared doxorubicin (DOX)-encapsulating liposomes containing L1 or L2, and clarified by confocal microscopic studies that the contents were rapidly transferred into both the cytoplasm and nucleus. Release of DOX from the endosomes mediated by the pH-responsive liposomes dramatically inhibited cancer cell growth. The L2-liposomes were slightly more effective than L1-liposomes as a drug delivery system. Intravenously injected L2-liposomes displayed blood persistence comparable to that of conventional phospholipid (PC)-based liposomes. Indeed, the antitumor efficacy of L2-liposomes was higher than that of PC-based liposomes against a xenograft breast cancer tumor in vivo. Thus, the high performance of L2-liposomes results from both efficient intracellular drug delivery and comparable blood persistence in comparison with the conventional PC-based liposomes in vitro and in vivo. Copyright 2009 Elsevier B.V. All rights reserved.

  9. Influence of cooking methods and storage time on lipid and protein oxidation and heterocyclic aromatic amines production in bacon.

    Science.gov (United States)

    Soladoye, O P; Shand, P; Dugan, M E R; Gariépy, C; Aalhus, J L; Estévez, M; Juárez, M

    2017-09-01

    This study aimed to examine the influence of cooking methods and pre-determined refrigerated storage days on the production of lipid oxidation (TBARS), protein oxidation (PROTOX) and heterocyclic aromatic amines (HAA) in bacon. Forty-four pork bellies selected from pigs varying in breed, sex and diets to introduce variability in composition were processed as bacon. Sliced-bacon was stored at 4°C either for 2 or 28days and these storage groups were cooked either with microwave or frying pan. Microwave led to significantly higher PROTOX (Pbacon (Pbacon (P0.05) by the cooking methods and storage times. Similarly, the fatty acid composition of pork belly did not significantly influence the production of HAA, TBARS and PROTOX produced in bacon during cooking. Overall, microwave cooking had lesser impact on the production of carcinogenic compounds in bacon with only minor impact on sensory attributes. Copyright © 2017. Published by Elsevier Ltd.

  10. Blue LED light exposure develops intracellular reactive oxygen species, lipid peroxidation, and subsequent cellular injuries in cultured bovine retinal pigment epithelial cells.

    Science.gov (United States)

    Nakanishi-Ueda, T; Majima, H J; Watanabe, K; Ueda, T; Indo, H P; Suenaga, S; Hisamitsu, T; Ozawa, T; Yasuhara, H; Koide, R

    2013-10-01

    The effects of blue light emitter diode (LED) light exposure on retinal pigment epithelial cells (RPE cells) were examined to detect cellular damage or change and to clarify its mechanisms. The RPE cells were cultured and exposed by blue (470 nm) LED at 4.8 mW/cm(2). The cellular viability was determined by XTT assay and cellular injury was determined by the lactate dehydrogenase activity in medium. Intracellular reactive oxygen species (ROS) generation was determined by confocal laser microscope image analysis using dihydrorhodamine 123 and lipid peroxidation was determined by 4-hydroxy-2-nonenal protein-adducts immunofluorescent staining (HNE). At 24 h after 50 J/cm(2) exposures, cellular viability was significantly decreased to 74% and cellular injury was significantly increased to 365% of control. Immediately after the light exposure, ROS generation was significantly increased to 154%, 177%, and 395% of control and HNE intensity was increased to 211%, 359%, and 746% of control by 1, 10, and 50 J/cm(2), respectively. These results suggest, at least in part, that oxidative stress is an early step leading to cellular damage by blue LED exposure and cellular oxidative damage would be caused by the blue light exposure at even lower dose (1, 10 J/cm(2)).

  11. Protective effects of Opuntia ficus-indica extract on ram sperm quality, lipid peroxidation and DNA fragmentation during liquid storage.

    Science.gov (United States)

    Allai, Larbi; Druart, Xavier; Öztürk, Mehmet; BenMoula, Anass; Nasser, Boubker; El Amiri, Bouchra

    2016-12-01

    The present study aimed to assess the phenolic composition of the acetone extract from Opuntia ficus indica cladodes (ACTEX) and its effects on ram semen variables, lipid peroxidation and DNA fragmentation during liquid storage at 5°C for up to 72h in skim milk and Tris egg yolk extenders. Semen samples from five rams were pooled extended with Tris-egg yolk (TEY) or skim milk (SM) extenders containing ACTEX (0%, 1%, 2%, 4% and 8%) at a final concentration of 0.8×10 9 sperm/ml and stored for up to 72h at 5°C. The sperm variables were evaluated at different time periods (8, 24, 48 and 72h). Sperm total motility and viability were superior in TEY than in SM whereas the progressive motility, membrane integrity, abnormality and spontaneous lipid peroxidation were greater in SM compared to TEY (P<0.05). The results also indicated that the inclusion of 1% ACTEX in the SM or TEY extender increased the sperm motility, viability, membrane integrity, and decreased the abnormality, lipids peroxidation up to 72h in storage compared to control group. Similarly, even at 72h of storage, 1% ACTEX can efficiently decrease the negative effects of liquid storage on sperm DNA fragmentation (P<0.05). In conclusion, SM and TEY supplemented with 1% of ACTEX can improve the quality of ram semen. Further studies are required to identify the active components in ACTEX involved in its effect on ram sperm preservation. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Intracellular cholesterol level regulates sensitivity of glioblastoma cells against temozolomide-induced cell death by modulation of caspase-8 activation via death receptor 5-accumulation and activation in the plasma membrane lipid raft.

    Science.gov (United States)

    Yamamoto, Yutaro; Tomiyama, Arata; Sasaki, Nobuyoshi; Yamaguchi, Hideki; Shirakihara, Takuya; Nakashima, Katsuhiko; Kumagai, Kosuke; Takeuchi, Satoru; Toyooka, Terushige; Otani, Naoki; Wada, Kojiro; Narita, Yoshitaka; Ichimura, Koichi; Sakai, Ryuichi; Namba, Hiroki; Mori, Kentaro

    2018-01-01

    Development of resistance against temozolomide (TMZ) in glioblastoma (GBM) after continuous treatment with TMZ is one of the critical problems in clinical GBM therapy. Intracellular cholesterol regulates cancer cell biology, but whether intracellular cholesterol is involved in TMZ resistance of GBM cells remains unclear. The involvement of intracellular cholesterol in acquired resistance against TMZ in GBM cells was investigated. Intracellular cholesterol levels were measured in human U251 MG cells with acquired TMZ resistance (U251-R cells) and TMZ-sensitive control U251 MG cells (U251-Con cells), and found that the intracellular cholesterol level was significantly lower in U251-R cells than in U251-Con cells. In addition, treatment by intracellular cholesterol remover, methyl-beta cyclodextrin (MβCD), or intracellular cholesterol inducer, soluble cholesterol (Chol), regulated TMZ-induced U251-Con cell death in line with changes in intracellular cholesterol level. Involvement of death receptor 5 (DR5), a death receptor localized in the plasma membrane, was evaluated. TMZ without or with MβCD and/or Chol caused accumulation of DR5 into the plasma membrane lipid raft and formed a complex with caspase-8, an extrinsic caspase cascade inducer, reflected in the induction of cell death. In addition, treatment with caspase-8 inhibitor or knockdown of DR5 dramatically suppressed U251-Con cell death induced by combination treatment with TMZ, MβCD, and Chol. Combined treatment of Chol with TMZ reversed the TMZ resistance of U251-R cells and another GBM cell model with acquired TMZ resistance, whereas clinical antihypercholesterolemia agents at physiological concentrations suppressed TMZ-induced cell death of U251-Con cells. These findings suggest that intracellular cholesterol level affects TMZ treatment of GBM mediated via a DR5-caspase-8 mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The fibrous form of intracellular inclusion bodies in recombinant variant fibrinogen-producing cells is specific to the hepatic fibrinogen storage disease-inducible variant fibrinogen.

    Science.gov (United States)

    Arai, Shinpei; Ogiwara, Naoko; Mukai, Saki; Takezawa, Yuka; Sugano, Mitsutoshi; Honda, Takayuki; Okumura, Nobuo

    2017-06-01

    Fibrinogen storage disease (FSD) is a rare disorder that is characterized by the accumulation of fibrinogen in hepatocytes and induces liver injury. Six mutations in the γC domain (γG284R, γT314P, γD316N, the deletion of γG346-Q350, γG366S, and γR375W) have been identified for FSD. Our group previously established γ375W fibrinogen-producing Chinese hamster ovary (CHO) cells and observed aberrant large granular and fibrous forms of intracellular inclusion bodies. The aim of this study was to investigate whether fibrous intracellular inclusion bodies are specific to FSD-inducible variant fibrinogen. Thirteen expression vectors encoding the variant γ-chain were stably or transiently transfected into CHO cells expressing normal fibrinogen Aα- and Bβ-chains or HuH-7 cells, which were then immunofluorescently stained. Six CHO and HuH-7 cell lines that transiently produced FSD-inducible variant fibrinogen presented the fibrous (3.2-22.7 and 2.1-24.5%, respectively) and large granular (5.4-25.5 and 7.7-23.9%) forms of intracellular inclusion bodies. Seven CHO and HuH-7 cell lines that transiently produced FSD-non-inducible variant fibrinogen only exhibit the large granular form. These results demonstrate that transiently transfected variant fibrinogen-producing CHO cells and inclusion bodies of the fibrous form may be useful in non-invasive screening for FSD risk factors for FSD before its onset.

  14. Pulmonary functions and sleep-related breathing disorders in lipid storage disease.

    Science.gov (United States)

    Bingöl, Züleyha; Tekce, Hacer Durmuş; Sağcan, Gülseren; Serdaroğlu, Piraye; Kıyan, Esen

    2018-03-01

    Pulmonary function abnormalities and sleep-related breathing disorders (SRBD) are frequent in subjects with several neuromuscular diseases but there is no data about lipid storage diseases (LSD). Therefore, we aimed to evaluate pulmonary functions and SRBD in adults with LSD. Pulmonary functions (forced expiratory volume (FEV 1 ), forced vital capacity (FVC), supine FVC, upright-supine FVC% change, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), peak cough flow (PCF)), arterial blood gases, and polysomnographic data of all subjects were evaluated. Twenty-five subjects with LSD were evaluated [17 males, 8 females; age 34.9 ± 15 years; BMI 26.5 ± 3.4 kg/m 2 ]. MIP was - 72.2 ± 32.7 cmH 2 O ( 45 mmHg). REM sleep had decreased in all subjects (10.2% ± 6.1). Obstructive sleep apnea (OSA) was found in 80% of the subjects (n = 20; 9 mild, 9 moderate, 2 severe). For subjects with OSA, apnea-hypopnea index (AHI) was 20.8 ± 15.9/h, oxygen desaturation index (ODI) was 11.9 ± 15.4/h, AHI REM was 30.6 ± 19.7/h, AHI NREM was 19.7 ± 16.6/h, ODI REM was 27.2 ± 26.1/h, and ODI NREM was 11.4 ± 15/h. Five subjects (20%) diagnosed as REM-related OSA. Nocturnal mean SpO 2 was 94.9% ± 1.7, lowest SpO 2 was 73.3% ± 13.9, and time spent with SpO 2 < 90% was 2.4% ± 7.2. In subjects with LSD, pulmonary function impairment, daytime hypercapnia and hypoxemia, and OSA, especially REM-related OSA, are frequent. Therefore, pulmonary functions and polysomnography should be performed routinely.

  15. Imaging heterogeneity of membrane and storage lipids in transgenic Camelina sativa seeds with altered fatty acid profiles.

    Science.gov (United States)

    Horn, Patrick J; Silva, Jillian E; Anderson, Danielle; Fuchs, Johannes; Borisjuk, Ljudmilla; Nazarenus, Tara J; Shulaev, Vladimir; Cahoon, Edgar B; Chapman, Kent D

    2013-10-01

    Engineering compositional changes in oilseeds is typically accomplished by introducing new enzymatic step(s) and/or by blocking or enhancing an existing enzymatic step(s) in a seed-specific manner. However, in practice, the amounts of lipid species that accumulate in seeds are often different from what one would predict from enzyme expression levels, and these incongruences may be rooted in an incomplete understanding of the regulation of seed lipid metabolism at the cellular/tissue level. Here we show by mass spectrometry imaging approaches that triacylglycerols and their phospholipid precursors are distributed differently within cotyledons and the hypocotyl/radicle axis in embryos of the oilseed crop Camelina sativa, indicating tissue-specific heterogeneity in triacylglycerol metabolism. Phosphatidylcholines and triacylglycerols enriched in linoleic acid (C18:2) were preferentially localized to the axis tissues, whereas lipid classes enriched in gadoleic acid (C20:1) were preferentially localized to the cotyledons. Manipulation of seed lipid compositions by heterologous over-expression of an acyl-acyl carrier protein thioesterase, or by suppression of fatty acid desaturases and elongases, resulted in new overall seed storage lipid compositions with altered patterns of distribution of phospholipid and triacylglycerol in transgenic embryos. Our results reveal previously unknown differences in acyl lipid distribution in Camelina embryos, and suggest that this spatial heterogeneity may or may not be able to be changed effectively in transgenic seeds depending upon the targeted enzyme(s)/pathway(s). Further, these studies point to the importance of resolving the location of metabolites in addition to their quantities within plant tissues. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  16. Development and lipid storage in Calanus euxinus from the Black and Marmara seas: Variabilities due to habitat conditions

    Science.gov (United States)

    Svetlichny, L. S.; Kideys, A. E.; Hubareva, E. S.; Besiktepe, S.; Isinibilir, M.

    2006-01-01

    Oil sac volume, gonad size and moulting patterns were investigated in the copepod Calanus euxinus inhabiting deep and shallow zones of the Black Sea and penetrating into the Marmara Sea. In summer the C. euxinus population in deep layers of the Black Sea was dominated by pre-diapause and diapausing postmoult copepodite stage V (CV) with small sexually undifferentiated gonads and mean lipid content of 14.1 ± 6.0% of body volume. The lipid content of deep-living females was 7.2 ± 4.2% of body volume. At the same time, intermoult and premoult CV with enlarged gonads and low lipid content (7.7 ± 5.1% of body volume) and females with oil sac volume of 1.4 ± 1.0% were found at shallow stations. Premoult CV with oil volume of 0.6 ± 0.8% and mature females with little visual evidence of substantial lipid storage dominated in the Marmara Sea. The differences in moulting patterns and oil sac volumes of C. euxinus from deep zones and shallow regions suggest that vertical migrations to the oxygen minimum zone (OMZ) are necessary for formation of large lipid reserves providing high reproductive potential of this species. On the basis of an energy balance model it was shown that under low phytoplankton concentration of about 30 μg C l - 1 preadults and adults migrating to the OMZ could accumulate lipids (up to 5% of body energy content daily), in contrast to copepods constrained to shallow oxic water columns of the Black Sea and from the Marmara Sea.

  17. Disruption of the Arabidopsis CGI-58 homologue produces Chanarin–Dorfman-like lipid droplet accumulation in plants

    OpenAIRE

    James, Christopher N.; Horn, Patrick J.; Case, Charlene R.; Gidda, Satinder K.; Zhang, Daiyuan; Mullen, Robert T.; Dyer, John M.; Anderson, Richard G. W.; Chapman, Kent D.

    2010-01-01

    CGI-58 is the defective gene in the human neutral lipid storage disease called Chanarin-Dorfman syndrome. This disorder causes intracellular lipid droplets to accumulate in nonadipose tissues, such as skin and blood cells. Here, disruption of the homologous CGI-58 gene in Arabidopsis thaliana resulted in the accumulation of neutral lipid droplets in mature leaves. Mass spectroscopy of isolated lipid droplets from cgi-58 loss-of-function mutants showed they contain triacylglycerols with common...

  18. Intracellular heavy metal nanoparticle storage: progressive accumulation within lymph nodes with transformation from chronic inflammation to malignancy

    Directory of Open Access Journals (Sweden)

    Tommaso Iannitti

    2010-11-01

    Full Text Available Tommaso Iannitti1, Stefania Capone2, Antonietta Gatti3, Frederico Capitani4, Cetta Francesco5,6, Beniamino Palmieri21Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK; 2Department of General Surgery and Surgical Specialties, 3Laboratory of Biomaterials, Department of Specialistic Surgeries, Head and Neck Medical School and Surgical Clinic, University of Modena and Reggio Emilia, Italy; 4Laboratory of Nanodiagnostics, San Vito, Modena, Italy 5Department of Surgery, University of Siena, Siena; 6Institute of Geriatrics, Pio Albergo Trivulzio Hospital, Milan, ItalyAbstract: A 25-year-old man had complained of sudden fever spikes for two years and his blood tests were within the normal range. In 1993, a surgical biopsy of swollen left inguinal lymph nodes was negative for malignancy, but showed reactive lymphadenitis and widespread sinus histiocytosis. A concomitant needle biopsy of the periaortic lymph nodes and a bone marrow aspirate were also negative. In 1994, after an emergency hospital admission because of a sport-related thoracic trauma, a right inguinal lymph node biopsy demonstrated Hodgkin’s lymphoma Stage IVB (scleronodular mixed cell subtype. Although it was improved by chemotherapy, the disease suddenly relapsed, and a further lymph node biopsy was performed in 1998 confirming the same diagnosis. Despite further treatment, the patient died of septic shock in 2004, at the age of 38 years. Retrospective analysis of the various specimens showed intracellular heavy metal nanoparticles within lymph node, bone marrow, and liver samples by field emission gun environmental scanning electron microscopy and energy dispersive spectroscopy. Heavy metals from environmental pollution may accumulate in sites far from the entry route and, in genetically conditioned individuals with tissue specificity, may act as cofactors for chronic inflammation or even malignant transformation. The present anecdotal report

  19. Regulation of fatty acid composition and lipid storage by thyroid hormone in mouse liver

    OpenAIRE

    Yao, Xuan; Hou, Sarina; Zhang, Duo; Xia, Hongfeng; Wang, Yu-Cheng; Jiang, Jingjing; Yin, Huiyong; Ying, Hao

    2014-01-01

    Background Thyroid hormones (THs) are potent hormones modulating liver lipid homeostasis. The perturbation of lipid homeostasis is a hallmark of non-alcoholic fatty liver disease (NAFLD), a very common liver disorder. It was reported that NAFLD patients were associated with higher incidence of hypothyroidism. However, whether abnormal thyroid function contributes to the pathogenesis of NAFLD remains unclear. Results We used in vivo models to investigate the influence of hypothyroidism and TH ...

  20. Fat storage-inducing transmembrane (FIT or FITM proteins are related to lipid phosphatase/phosphotransferase enzymes

    Directory of Open Access Journals (Sweden)

    Matthew J Hayes

    2017-12-01

    Full Text Available Fat storage-inducing transmembrane (FIT or FITM proteins have been implicated in the partitioning of triacylglycerol to lipid droplets and the budding of lipid droplets from the ER. At the molecular level, the sole relevant interaction is that FITMs directly bind to triacyglycerol and diacylglycerol, but how they function at the molecular level is not known. Saccharomyces cerevisiae has two FITM homologues: Scs3p and Yft2p. Scs3p was initially identified because deletion leads to inositol auxotrophy, with an unusual sensitivity to addition of choline. This strongly suggests a role for Scs3p in phospholipid biosynthesis. Looking at the FITM family as widely as possible, we found that FITMs are widespread throughout eukaryotes, indicating presence in the last eukaryotic common ancestor. Protein alignments also showed that FITM sequences contain the active site of lipid phosphatase/phosphotransferase (LPT enzymes. This large family transfers phosphate-containing headgroups either between lipids or in exchange for water. We confirmed the prediction that FITMs are related to LPTs by showing that single amino-acid substitutions in the presumptive catalytic site prevented their ability to rescue growth of the mutants on low inositol/high choline media when over-expressed. The substitutions also prevented rescue of other phenotypes associated with loss of FITM in yeast, including mistargeting of Opi1p, defective ER morphology, and aberrant lipid droplet budding. These results suggest that Scs3p, Yft2p and FITMs in general are LPT enzymes involved in an as yet unknown critical step in phospholipid metabolism.

  1. Effect of irradiation and soaking in BHT and sodium pyrophosphate on meat proteins and lipids during cold storage

    International Nuclear Information System (INIS)

    Hassan, I.M.; Emam, O.A.

    1988-01-01

    The effect of irradiation treatments up to 10 KGy, soaking in a solution containing 0.5% Na-pyrophosphate and 250 ppm butylated hydroxy toluene (BHT) and a combination of both treatments on the nitrogen content and solubility, protein fractions and lipids stability in beef steaks during cold storage at 4 ± 1°C was followed until the samples were rejected by sensory evaluation. The least effective radiation doses for soluble protein nitrogen (SPN), total soluble nitrogen (TSN) and total nitrogen (TN) were 2, 5 and 10 KGy, respectively. Such effects were proportionally related to the applied dose. The loss in nitrogen compounds and/or their solubility which occurred upon irradiation appeared to be retarded by soaking treatment. Irradiation treatments induced additional protein fraction which seems to be originated from the sarcoplasmic proteins. After the resolution of rigor mortis, the incremental rate of nitrogen extractability was inversely related to the irradiation dose. Another protein fraction was detected only in the 10 KGy irradiated samples after 14 days of cold storage which might be originating from fibrillar proteins as a result of its interaction with some lipid oxidation products. However, soaking treatment itself caused extensive changes in protein fractions, in contrast, protection from radiation and radiation after-effects were observed

  2. Metabolic encephalopathy and lipid storage myopathy associated with a presumptive mitochondrial fatty acid oxidation defect in a dog

    Directory of Open Access Journals (Sweden)

    Vanessa R Biegen

    2015-11-01

    Full Text Available A 1-year-old spayed female Shih Tzu presented for episodic abnormalities of posture and mentation. Neurologic examination was consistent with a bilaterally symmetric multifocal encephalopathy. The dog had a waxing-and-waning hyperlactemia and hypoglycemia. Magnetic resonance imaging revealed bilaterally symmetric cavitated lesions of the caudate nuclei with less severe abnormalities in the cerebellar nuclei. Empirical therapy was unsuccessful and the patient was euthanized. Post-mortem histopathology revealed bilaterally symmetric necrotic lesions of the caudate and cerebellar nuclei and multi-organ lipid accumulation, including a lipid storage myopathy. Malonic aciduria and ketonuria were found on urinary organic acid screen. Plasma acylcarnitine analysis suggested a fatty acid oxidation defect. Fatty acid oxidation disorders are inborn errors of metabolism documented in humans, but poorly described in dogs. Although neurologic signs have been described in humans with this group of diseases, descriptions of advanced imaging and histopathology are severely lacking. This report suggests that abnormalities of fatty acid metabolism may cause severe, bilateral gray matter necrosis and lipid accumulation in multiple organs including the skeletal muscles, liver, and kidneys. Veterinarians should be aware that fatty acid oxidation disorders, although potentially fatal, may be treatable. A timely definitive diagnosis is essential in guiding therapy.

  3. Studies on RBC lipid and protein phosphorylation during blood bank storage

    International Nuclear Information System (INIS)

    Dumaswala, U.J.; Bryan, D.J.; Greenwalt, T.J.

    1986-01-01

    Recent evidence has suggested that phosphoinositides play a significant role in maintaining membrane structure and function. Their importance during blood bank storage is not understood. They have performed preliminary studies of the phosphoinositide synthetic pathway enzymes of RBC during blood bank storage. At 0 and 35 days of storage leaky ghosts were prepared and incubated with [γ- 32 P]ATP for 5 minutes at 30 C. One aliquot was subjected to acidified solvent extraction and thin layer chromatography. The labeled phosphoinositide -4,5 biphosphate (PIP 2 ), phosphoinositide-4 phosphate (PIP) and phosphatidic acid (PA) spots were scraped and counted by liquid scintillation spectrometry. Another aliquot was used for SDS-PAGE and the radioactivity associated with the β-spectrin was measured. These experiments suggest a decrease in RBC phosphoinositol and PIP-Kinases and β-spectrin kinase activities during blood bank storage. Further studies are being done to evaluate significance of these observations

  4. Non-polar lipids accumulate during storage of transfusion products and do not contribute to the onset of transfusion-related acute lung injury.

    Science.gov (United States)

    Peters, A L; Vervaart, M A T; van Bruggen, R; de Korte, D; Nieuwland, R; Kulik, W; Vlaar, A P J

    2017-01-01

    The accumulation of non-polar lipids arachidonic acid, 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE and 15-HETE during storage of transfusion products may play a role in the onset of transfusion-related acute lung injury (TRALI), a syndrome of respiratory distress after transfusion. We investigated non-polar lipid accumulation in red blood cells (RBCs) stored for 42 days, plasma stored for 7 days at either 4 or 20°C and platelet (PLT) transfusion products stored for 7 days. Furthermore, we investigated whether transfusion of RBCs with increased levels of non-polar lipids induces TRALI in a 'two-hit' human volunteer model. All products were produced following Dutch Blood Bank protocols and are according to European standards. Non-polar lipids were measured with high-performance liquid chromotography followed by mass spectrometry. All non-polar lipids increased in RBCs after 21 days of storage compared to baseline. The non-polar lipid concentration in plasma increased significantly, and the increase was even more pronounced in products stored at 20°C. In platelets, baseline levels of 5-HETE and 15-HETE were higher than in RBCs or plasma. However, the non-polar lipids did not change significantly during storage of PLT products. Infusion of RBCs with increased levels of non-polar lipids did not induce TRALI in LPS-primed human volunteers. We conclude that non-polar lipids accumulate in RBC and plasma transfusion products and that accumulation is temperature dependent. Accumulation of non-polar lipids does not appear to explain the onset of TRALI (Dutch Trial Register - NTR4455). © 2016 International Society of Blood Transfusion.

  5. Influence of chain length of pyrene fatty acids on their uptake and metabolism by Epstein-Barr-virus-transformed lymphoid cell lines from a patient with multisystemic lipid storage myopathy and from control subjects.

    Science.gov (United States)

    Radom, J; Salvayre, R; Levade, T; Douste-Blazy, L

    1990-01-01

    The uptake and intracellular metabolism of 4-(1-pyrene)butanoic acid (P4), 10-(1-pyrene)decanoic acid (P10) and 12-(1-pyrene)dodecanoic acid (P12) were investigated in cultured lymphoid cell lines from normal individuals and from a patient with multisystemic lipid storage myopathy (MLSM). The cellular uptake was shown to be dependent on the fatty-acid chain length, but no significant difference in the uptake of pyrene fatty acids was observed between MLSM and control lymphoid cells. After incubation for 1 h the distribution of fluorescent fatty acids taken up by the lymphoid cell lines also differed with the chain length, most of the fluorescence being associated with phospholipid and triacylglycerols. In contrast with P10 and P12, P4 was not incorporated into neutral lipids. When the cells were incubated for 24 h with the pyrene fatty acids, the amount of fluorescent lipids synthesized by the cells was proportional to the fatty acid concentration in the culture medium. After a 24 h incubation in the presence of P10 or P12, at any concentration, the fluorescent triacylglycerol content of MLSM cells was 2-5-fold higher than that of control cells. Concentrations of pyrene fatty acids higher than 40 microM seemed to be more toxic for mutant cells than for control cells. This cytotoxicity was dependent on the fluorescent-fatty-acid chain length (P12 greater than P10 greater than P4). Pulse-chase experiments permitted one to demonstrate the defect in the degradation of endogenously biosynthesized triacylglycerols in MLSM cells (residual activity was around 10-25% of controls on the basis of half-lives and initial rates of P10- or P12-labelled-triacylglycerol catabolism); MLSM lymphoid cells exhibited a mild phenotypic expression of the lipid storage (less severe than that observed in fibroblasts). P4 was not utilized in the synthesis of triacylglycerols, and thus did not accumulate in MLSM cells: this suggests that natural short-chain fatty acids might induce a lesser

  6. Stability of selected serum hormones and lipids after long-term storage in the Janus Serum Bank.

    Science.gov (United States)

    Gislefoss, Randi E; Grimsrud, Tom K; Mørkrid, Lars

    2015-04-01

    The potential value of a biobank depends on the quality of the samples, i.e. how well they reflect the biological or biochemical state of the donors at the time of sampling. Documentation of sample quality has become a particularly important issue for researchers and users of biobank studies. The aim of this study was to investigate the long-term stability of selected components: cholesterol, high density cholesterol (HDLC), low density cholesterol (LDLC), apolipoprotein A1 (apo-A1), apolipoprotein B (apo B), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH) and free thyroxin (FT4). Samples, stored at -25°C, from 520 men aged 40-49 years at blood sampling distributed in equally sized groups (n=130) according to length of storage, 0, 4, 17 and 29 years, respectively, were used in a cross sectional design. The freshly collected serum samples were used as a reference group to calculate storage related changes. The differences between fresh samples and samples stored for 29 years were substantial for apo-A1 (+12%), apo-B (+22.3%), HDLC (-69.2%), LDLC (+31.3%), and PRL (-33.5%), while total cholesterol, FSH, LH, TSH and FT4 did not show any significant difference. The study showed large differences in serum level of the selected components. The lipids and apolipoproteins were all changed except for total cholesterol. Most hormones investigated (FSH, LH, TSH and FT4) proved to be stable after 29 years of storage while PRL showed sign of degradation. The observed differences are probably due to long-term storage effects and/or external factors (i.e. diet and smoking). Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  7. Restarting stalled autophagy a potential therapeutic approach for the lipid storage disorder, Niemann-Pick type C1 disease.

    Science.gov (United States)

    Sarkar, Sovan; Maetzel, Dorothea; Korolchuk, Viktor I; Jaenisch, Rudolf

    2014-06-01

    Autophagy is essential for cellular homeostasis and its dysfunction in human diseases has been implicated in the accumulation of misfolded protein and in cellular toxicity. We have recently shown impairment in autophagic flux in the lipid storage disorder, Niemann-Pick type C1 (NPC1) disease associated with abnormal cholesterol sequestration, where maturation of autophagosomes is impaired due to defective amphisome formation caused by failure in SNARE machinery. Abrogation of autophagy also causes cholesterol accumulation, suggesting that defective autophagic flux in NPC1 disease may act as a primary causative factor not only by imparting its deleterious effects, but also by increasing cholesterol load. However, cholesterol depletion treatment with HP-β-cyclodextrin impedes autophagy, whereas pharmacologically stimulating autophagy restores its function independent of amphisome formation. Of potential therapeutic relevance is that a low dose of HP-β-cyclodextrin that does not perturb autophagy, coupled with an autophagy inducer, may rescue both the cholesterol and autophagy defects in NPC1 disease.

  8. The perilipin homologue, lipid storage droplet 2, regulates sleep homeostasis and prevents learning impairments following sleep loss.

    Directory of Open Access Journals (Sweden)

    Matthew S Thimgan

    2010-08-01

    Full Text Available Extended periods of waking result in physiological impairments in humans, rats, and flies. Sleep homeostasis, the increase in sleep observed following sleep loss, is believed to counter the negative effects of prolonged waking by restoring vital biological processes that are degraded during sleep deprivation. Sleep homeostasis, as with other behaviors, is influenced by both genes and environment. We report here that during periods of starvation, flies remain spontaneously awake but, in contrast to sleep deprivation, do not accrue any of the negative consequences of prolonged waking. Specifically, the homeostatic response and learning impairments that are a characteristic of sleep loss are not observed following prolonged waking induced by starvation. Recently, two genes, brummer (bmm and Lipid storage droplet 2 (Lsd2, have been shown to modulate the response to starvation. bmm mutants have excess fat and are resistant to starvation, whereas Lsd2 mutants are lean and sensitive to starvation. Thus, we hypothesized that bmm and Lsd2 may play a role in sleep regulation. Indeed, bmm mutant flies display a large homeostatic response following sleep deprivation. In contrast, Lsd2 mutant flies, which phenocopy aspects of starvation as measured by low triglyceride stores, do not exhibit a homeostatic response following sleep loss. Importantly, Lsd2 mutant flies are not learning impaired after sleep deprivation. These results provide the first genetic evidence, to our knowledge, that lipid metabolism plays an important role in regulating the homeostatic response and can protect against neuronal impairments induced by prolonged waking.

  9. PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

    Science.gov (United States)

    Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; Duross, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

    2016-08-01

    2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1-/-) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1-/- cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders.

  10. Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies.

    Science.gov (United States)

    Aerts, Johannes M F G; Kallemeijn, Wouter W; Wegdam, Wouter; Joao Ferraz, Maria; van Breemen, Marielle J; Dekker, Nick; Kramer, Gertjan; Poorthuis, Ben J; Groener, Johanna E M; Cox-Brinkman, Josanne; Rombach, Saskia M; Hollak, Carla E M; Linthorst, Gabor E; Witte, Martin D; Gold, Henrik; van der Marel, Gijs A; Overkleeft, Herman S; Boot, Rolf G

    2011-06-01

    A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, recently developed chemical tools allowing specific visualization of enzymatically active lysosomal glucocerebrosidase are described. Such probes, coined inhibodies, offer entirely new possibilities for more sophisticated molecular diagnosis, enzyme replacement therapy monitoring, and fundamental research.

  11. Development of volatile compounds during storage at various conditions of different lipid containing lip balm products

    DEFF Research Database (Denmark)

    Thomsen, Birgitte Raagaard; Horn, A. F.; Hyldig, Grethe

    ; the degree of unsaturation, the content of antioxidants and the quality of the raw materials. When stored in the homes of consumers the lip balms may be exposed to relatively high temperatures and light. Hence, especially lip balms sold in countries with a warm climate can undergo lipid oxidation and develop...... for their development of volatile compounds by dynamic headspace gas chromatography-mass spectrometry and peroxide value, and compared to samples stored at 2°C in the dark. In addition, sensory analyses were carried out to assess the off-odours developed in the samples. The result showed that addition of iron increased...

  12. Lipid oxidation in herring fillets (Clupea harengus) during ice storage measured by a commercial hybrid gas-sensor array system.

    Science.gov (United States)

    Haugen, John-Erik; Undeland, Ingrid

    2003-01-29

    Volatile compounds released from herring fillets (Clupea harengus) during 15 days of storage on ice have been measured with a commercial hybrid gas-sensor array system. Using partial least-squares regression modeling, the sensor responses were correlated with data from chemical analyses (lipid oxidation products and antioxidants) and sensory analyses (odor). Eight of the 16 sensors proved significant in the correlation studies: 6 metal oxide semiconductor field effect transistor (MOSFET) sensors and 2 Taguchi type sensors. Correlation coefficients for chemical and sensory data ranged from 0.9 to 0.98 and from 0.49 to 0.92, respectively, with 0.92 referring to both "sharp/acrid" and "rancid" odors. Prediction errors ranged from 8 to 14% and from 11 to 25% for the chemical and sensory measures, respectively. That the prediction errors for oxidation product formation (5-9%) were close to the analytical errors of the chemical reference methods indicated close to "optimum" performance of the gas-sensor system. The sensor system predicted the storage time of the herring with a 1-day error. Results illustrate high potential of the gas-sensor technology in rapid nondestructive quality determination of ice-stored herring.

  13. Lipid-storage myopathy and respiratory insufficiency due to ETFQO mutations in a patient with late-onset multiple acyl-CoA dehydrogenation deficiency

    DEFF Research Database (Denmark)

    Olsen, R K J; Pourfarzam, M; Morris, A A M

    2004-01-01

    We report a patient with lipid-storage myopathy due to multiple acyl-CoA dehydrogenation deficiency (MADD). Molecular genetic analysis showed that she was compound heterozygous for mutations in the gene for electron transfer flavoprotein:ubiquinone oxidoreductase (ETFQO). Despite a good initial r...

  14. Effect of dietary ethanol extracts of mango (Mangifera indica L.) on lipid oxidation and the color of chicken meat during frozen storage.

    Science.gov (United States)

    Freitas, Ednardo Rodrigues; da Silva Borges, Ângela; Pereira, Ana Lúcia Fernandes; Abreu, Virgínia Kelly Gonçalves; Trevisan, Maria Teresa Salles; Watanabe, Pedro Henrique

    2015-12-01

    The aim of this study was to evaluate the dietary effect of mango extracts on lipid stability and the coloring of broiler chicken breast meat during frozen storage. The treatments consisted of broiler chicken diet without antioxidants (control) and diets containing antioxidants: 200 ppm of butylated hydroxytoluene (BHT), 200 ppm of mango peel extract (MPE), 400 ppm of MPE, 200 ppm of mango seed extract (MSE), and 400 ppm of MSE. The broiler breasts were stored for 90 days and analysis of lipid oxidation and color was performed every 30 days. The thiobarbituric acid reactive substances values increased during storage and at 90 days, but the 400 ppm MSE treatment yielded lower values, indicating greater antioxidant activity. During storage, the lightness values decreased and the redness increased. Additions of 200 ppm BHT and 400 ppm MPE increased yellowness at 60 days of storage. Thus, mango peel and seed extracts added to broiler chicken diets reduce lipid oxidation and maintain color in breast meat during frozen storage, with mango seed extract at 400 ppm being the most effective. © 2015 Poultry Science Association Inc.

  15. Marine Lipids (Omega-3 Oil) - Stability of Oil and Enriched Products During Production and Storage

    DEFF Research Database (Denmark)

    Nielsen, Nina Skall

    2015-01-01

    off-flavours and gives rise to unhealthy compounds such as free radicals and reactive aldehydes. Necessary prerequisites for successful development of omega-3 enriched products are that the oil used for enrichment is of a high quality and low in oxidation products and that oxidation of the lipids...... oxidation. As processing will often cause extra oxidative stress to the omega-3 oil, extrinsic factors are especially important to consider during processing. Due to the complexity of multiphase foods, it is very difficult to predict the oxidative stability and therefore the behaviour and efficacy...... of antioxidants in omega-3 oil enriched products and optimal composition and processing conditions must be evaluated for each product....

  16. Effects of diet, packaging, and irradiation on protein oxidation, lipid oxidation, and color of raw broiler thigh meat during refrigerated storage.

    Science.gov (United States)

    Xiao, S; Zhang, W G; Lee, E J; Ma, C W; Ahn, D U

    2011-06-01

    This study was designed to evaluate the effects of dietary treatment, packaging, and irradiation singly or in combination on the oxidative stability of broiler chicken thigh meat. A total of 120 four-week-old chickens were divided into 12 pens (10 birds/pen), and 4 pens of broilers were randomly assigned to a control oxidized diet (5% oxidized oil) or an antioxidant-added diet [500 IU of vitamin E + 200 mg/kg of butylated hydroxyanisole (BHA)] and fed for 2 wk. After slaughter, thigh meats were separated, ground, packaged in either oxygen-permeable or oxygen-impermeable vacuum bags, and irradiated at 0 or 3 kGy. Lipid oxidation (TBA-reactive substances), protein oxidation (carbonyl), and color of the meat were measured at 1, 4, and 7 d of refrigerated storage. The lipid and protein oxidation of thigh meats from birds fed the diet supplemented with antioxidants (vitamin E + BHA) was significantly lower than the lipid and protein oxidation of birds fed the control diet, whereas the lipid and protein oxidation of broilers fed the oxidized oil diet was higher than that of birds fed the control diet. Vacuum packaging slowed, but irradiation accelerated, the lipid and protein oxidation of thigh meat during storage. Dietary antioxidants (vitamin E + BHA) and irradiation treatments showed a stronger effect on lipid oxidation than on protein oxidation. A significant correlation between lipid and protein oxidation in meat was found during storage. Dietary supplementation of vitamin E + BHA and the irradiation treatment increased the lightness and redness of thigh meat, respectively. It is suggested that appropriate use of dietary antioxidants in combination with packaging could be effective in minimizing oxidative changes in irradiated raw chicken thigh meat.

  17. Metabolic networks and bioenergetics of Aurantiochytrium sp. B-072 during storage lipid formation

    Directory of Open Access Journals (Sweden)

    Montri Chaisawang

    2012-09-01

    Full Text Available Baffled shake flask cultivation of Aurantiochytrium sp. B-072 was carried out at in a glucose-monosodium glutamate mineral medium at different C/N-ratios (30-165 with glucose fixed at 90 g/L. With increasing C/N-ratio, a modest increase in lipid content (60 to 73 % w/w was observed whereas fat-free biomass decreased but overall biomass showed little variation. FA-profiles were not affected to a large extent by C/N-ratio and absolute docosahexaenoic (DHA-levels fell in narrow range (5-6 g/L. However at C/N > 64 a rapid decrease in lipid synthetic rate and/or incomplete glucose utilization occurred. Glucose and FA-fluxes based on fat-free biomass peaked at a C/N ratio of 56. This condition was chosen for calculation of the redox balance (NAD(PH and energy (ATP requirement and to estimate the in vivo P/O ratio during the main period of fatty acid biosynthesis. Several models with different routes for NADPH, acetyl-CoA formation and re-oxidation of OAA formed via ATP-citrate lyase were considered as these influence the redox- and energy balance. As an example, using a commonly shown scheme whereby NADPH is supplied by a cytosolic "transhydrogenase cycle" (pyruvate-OAA-malate-pyruvate and OAA formed by ATP-citrate lyase is recycled via import into the mitochondria as malate, the calculated NADPH-requirement amounted to 5.5 with an ATP-demand of 10.5 mmol/(g fat-free biomass x h and an in vivo P/O-ratio (not including non-growth associated maintenance of 1.6. The lowest ATP requirement is found when acetyl-CoA would be transported directly from the mitochondria to the cytosol by carnitine acetyltransferase. Assay of some enzymes critical for NADPH supply indicates that activity of glucose-6-phosphate dehydrogenase, the first enzyme in the HMP pathway, is far insufficient for the required NADPH-flux and malic enzyme must be a major source. Activity of the latter (ca. 300 mU/mg protein far exceeds that in oleaginous fungi and yeast.

  18. Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by Lippia alba Essential Oils.

    Science.gov (United States)

    Montero-Villegas, Sandra; Polo, Mónica; Galle, Marianela; Rodenak-Kladniew, Boris; Castro, María; Ves-Losada, Ana; Crespo, Rosana; García de Bravo, Margarita

    2017-01-01

    The essential oils (EOs) of Lippia alba, an herb extensively used as a folk medicine in Latin America, are today promoted as an effective means of eliminating problems caused by hyperlipemia. We hypothesized that L.alba EOs inhibited cholesterol and triacylglycerols synthesis and decreased the intracellular depots of those lipids (lipid droplets), mechanisms involving the induction of a hypolipidemic response. Our aim was, therefore, to evaluate the hypolipogenic capability of the EOs of four L. alba chemotypes on liver-derived (HepG2) and non-liver (A549) human cell lines and to identify the potential biochemical targets of those chemotypes, particularly within the mevalonate pathway (MP). [ 14 C]Acetate was used as radioactive precursor for assays. Lipid analyses were performed by thin-layer and capillary gas chromatography, lipid droplets analyzed by fluorescence microscopy, and HMGCR levels determined by Western blot. In both cell lines, all four chemotypes exerted hypocholesterogenic effects within a concentration range of 3.2-32 µg/mL. Nonsaponifiable lipids manifested a decrease in incorporation of [ 14 C]acetate into squalene, lanosterol, lathosterol, and cholesterol, but not into ubiquinone, thus suggesting an inhibition of enzymes in the MP downstream from farnesyl pyrophosphate. The tagetenone chemotype, the most efficacious hypocholesterogenic L. alba EO, lowered HMGCR protein levels; inhibited triacylglycerols, cholesteryl esters, and phospholipids synthesis; and diminished lipid droplets in size and volume. These results revealed that L. alba EOs inhibited different lipogenic pathways and such lipid-lowering effects could prove essential to prevent cardiovascular diseases.

  19. I. Lipid metabolism stimulated by altered intracellular calcium in cultured fibroblasts. II. Regulation of the activity of rat adipose tissue lipoprotein lipase

    International Nuclear Information System (INIS)

    Chang Wang, Huei-Hsiang Lisa.

    1988-01-01

    The cell killing process of 3T3 Swiss mouse fibroblasts stimulated by Ca 2+ plus A23187, a Ca 2+ ionophore has been studied. The aim of this research is to understand the biochemical mechanism of this process, i.e, to elucidate the step involved and to characterize the enzymes involved with each steps in the lipid metabolism stimulated in cultured fibroblasts undergoing a toxic death response. Parallel 3T3 cultures biosynthetically labeled with lipid precursors were examined under Ca 2+ -mediated killing conditions. Labeled lipids were extracted and analyzed by thin-layer chromatography and autoradiography. Evidence for activation of a phosphatidylinositol-specific phospholipase C has been obtained in injured 3T3 cells labeled with [ 3 H]glycerol and [ 3 H]inositol. To simplify the system for studying the lipoprotein lipase reaction, our laboratory prepared the chromophore containing a substrate: 1,2-dipalmitoyl-3-β-2-furylacryloyltriacylglycerol (DPFATG). By using this artificial lipid we could readily investigate the lipoprotein lipase reactions, since the absorbance change directly represents the hydrolysis of the chromophoric side chain of the substrate

  20. Preservative effect of Asparagus racemosus: A novel additive for bioactive edible films for improved lipid oxidative stability and storage quality of meat products.

    Science.gov (United States)

    Noor, Sabahu; Bhat, Z F; Kumar, Sunil; Mudiyanselage, Reshan J

    2018-02-02

    Asparagus racemosus was used as a bioactive ingredient for the development of a novel calcium alginate edible film with preservative potential for improved lipid oxidative stability and storage quality of meat products. Chevon sausages were used as a model system and were aerobically packaged in the edible films incorporated with A. racemosus viz. T 0 (0.0%), T 1 (1.0%) and T 2 (2.0%) and were stored under refrigerated (4 ± 1 °C) conditions. Products packaged in T 1 and T 2 edible films exhibited significantly (P films. Significantly (P films. A. racemosus added antioxidant and antimicrobial properties to the developed films which improved the lipid oxidative stability and storage quality of the model meat product. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C.

    Science.gov (United States)

    Lopez, Manuel E; Klein, Andrés D; Hong, Jennifer; Dimbil, Ubah J; Scott, Matthew P

    2012-07-01

    Chronic systemic inflammation is thought to be a major contributor to metabolic and neurodegenerative diseases. Since inflammatory components are shared among different disorders, targeting inflammation is an attractive option for mitigating disease. To test the significance of inflammation in the lipid storage disorder (LSD) Niemann-Pick C (NPC), we deleted the macrophage inflammatory gene Mip1a/Ccl3 from NPC diseased mice. Deletion of Ccl3 had been reported to delay neuronal loss in Sandhoff LSD mice by inhibiting macrophage infiltration. For NPC mice, in contrast, deleting Ccl3 did not retard neurodegeneration and worsened the clinical outcome. Depletion of visceral tissue macrophages also did not alter central nervous system (CNS) pathology and instead increased liver injury, suggesting a limited macrophage infiltration response into the CNS and a beneficial role of macrophage activity in visceral tissue. Prevention of neuron loss or liver injury, even at late stages in the disease, was achieved through specific rescue of NPC disease in neurons or in liver epithelial cells, respectively. Local epithelial cell correction was also sufficient to reduce the macrophage-associated pathology in lung tissue. These results demonstrate that elevated inflammation and macrophage activity does not necessarily contribute to neurodegeneration and tissue injury, and LSD defects in immune cells may not preclude an appropriate inflammatory response. We conclude that inflammation remains secondary to neuronal and epithelial cell dysfunction and does not irreversibly contribute to the pathogenic cascade in NPC disease. Without further exploration of possible beneficial roles of inflammatory mediators, targeting inflammation may not be therapeutically effective at ameliorating disease severity.

  2. Fatty acid profile, color and lipid oxidation of organic fermented sausage during chilling storage as influenced by acid whey and probiotic strains addition

    Directory of Open Access Journals (Sweden)

    Karolina Maria Wójciak

    2015-02-01

    Full Text Available Organic fermented sausages typically spoil during long-term storage due to oxidative rancidity. The application of natural antioxidants to meat stuffing is a major practice intended to inhibit the oxidation process and color changes. This study aimed to assess the effect of two unusual starter cultures: three probiotic strains (Lactobacillus casei LOCK 0900, Lactobacillus casei LOCK 0908 and Lactobacillus paracasei LOCK 0919 and lactic acid bacteria from acid whey on model fermented sausage type products focusing on oxidative stability by measuring instrumental color (L*, a*, b* values, conjugated dienes (CD, TBARS immediately after 21 days of ripening (0 and after 90 and 180 days of refrigerated storage (4 ºC. Determination of fatty acid composition, in meat product was performed after ripening and after 180 days of storage. At the end of the storage period, the salted sausages were characterized by the same content of polyunsaturated fatty acids (PUFA compared to cured samples. The addition of acid whey and a mixture of probiotic strains to nitrite-free sausage formulation was barely able to protect lipids against oxidation in comparison to nitrite during vacuum storage. Surprisingly, the use of acid whey has an influence on the desired red-pinkish color of organic fermented sausage after ripening and after 180 days of storage period.

  3. Lipid recovery from a vegetable oil emulsion using microbial enrichment cultures.

    Science.gov (United States)

    Tamis, Jelmer; Sorokin, Dimitry Y; Jiang, Yang; van Loosdrecht, Mark C M; Kleerebezem, Robbert

    2015-01-01

    Many waste streams have a relatively high vegetable oil content, which is a potential resource that should be recovered. Microbial storage compound production for the recovery of lipids from lipid-water emulsions with open (unsterilized) microbial cultures was investigated in a sequencing batch reactor using a diluted vegetable oil emulsion as model substrate. After feeding, triacylglycerides (TAG) were accumulated intracellular by the microbial enrichment culture and subsequently used for growth in the remainder of the sequencing batch cycle. Roughly 50% of the added TAG could be recovered as intracellular lipids in this culture. The maximum lipid storage capacity of the enrichment culture was 54% on volatile suspended solids (VSS) mass basis in a separate fed-batch accumulation experiment. The microbial community was dominated by a lipolytic fungus, Trichosporon gracile, that was responsible for intracellular lipid accumulation but also a significant fraction of lipolytic and long chain fatty-acid-utilizing bacteria was present. Herewith, we demonstrate an effective strategy for enrichment of a microbial community that can accumulate significant amounts of lipids from wastewaters without the need for sterilization of substrates or equipment. Further optimization of this process will make recovery of lipids from wastewater possible.

  4. Lipid Storage Diseases

    Science.gov (United States)

    ... that cause twisting and repetitive movements or abnormal postures). Angiokeratomas may develop on the lower part of ... of hearing leading to deafness, difficulty in swallowing, blindness, cherry-red spots in the retinas, and some ...

  5. Oxidation of lipid and protein in horse mackerel (Trachurus trachurus) mince and washed minces during processing and storage

    DEFF Research Database (Denmark)

    Eymard, Sylvie; Baron, Caroline; Jacobsen, Charlotte

    2009-01-01

    : M1, M2 and M3, with one, two and three washing steps, respectively. The different products were characterised (i.e. lipid content, protein, water, iron, fatty acid profile and tocopherol content) and analysed for protein and lipid oxidation in order to investigate the impact of the washing steps...... was followed by determination of protein solubility, protein thiol groups and protein carbonyl groups using colorimetric methods as well as western blotting for protein carbonyl groups. Lipid and protein oxidation markers indicated that both lipid and protein oxidation took place during processing...

  6. Serotonin storage pools in basophil leukemia and mast cells: characterization of two types of serotonin binding protein and radioautographic analysis of the intracellular distribution of [3H]serotonin

    International Nuclear Information System (INIS)

    Tamir, H.; Theoharides, T.C.; Gershon, M.D.; Askenase, P.W.

    1982-01-01

    The binding of serotonin to protein(s) derived from rat basophil leukemia (RBL) cells and mast cells was studied. Two types of serotonin binding protein in RBL cells was found. These proteins differed from one another in molecular weight and eluted in separate peaks from sephadex G-200 columns. Peak I protein (KD = 1.9 x 10 -6 M) was a glycoprotein that bound to concanavalin A (Con A); Peak II protein (KD 1 = 4.5 x 10 - 8 M; KD 2 = 3.9 x 10 -6 M) did not bind to Con A. Moreover, binding of [ 3 H]serotonin to protein of Peak I was sensitive to inhibition by reserpine, while binding of [ 3 H]serotonin to protein of Peak II resisted inhibition by that drug. Other differences between the two types of binding protein were found, the most significant of which was the far more vigorous conditions of homogenization required to extract Peak I than Peak II protein. Electron microscope radioautographic analysis of the intracellular distribution of [ 3 H] serotonin taken up in vitro by RBL cells or in vivo by murine mast cells indicated that essentially all of the labeled amine was located in cytoplasmic granules.No evidence for a pool in the cytosol was found and all granules were capable of becoming labeled. The presence of two types of intracellular serotonin binding proteins in these cells may indicate that there are two intracellular storage compartments for the amine. Both may be intragranular, but Peak I protein may be associated with the granular membrane while Peak II protein may be more free within the granular core. Different storage proteins may help to explain the differential release of amines from mast cell granules

  7. Effect of temperature towards lipid oxidation and non-enzymatic browning reactions in krill oil upon storage

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Bruheim, I.; Haugsgjerd, B.O.

    2014-01-01

    was assessed by peroxide value and anisidine value, measurement of lipid derived volatiles, lipid classes and antioxidants. The non-enzymatic browning reactions were assessed through the measurement of pyrroles, free amino acids content and Strecker-derived volatiles. The increase of incubation temperature...

  8. In vivo hepatic lipid quantification using MRS at 7 Tesla in a mouse model of glycogen storage disease type 1a

    Science.gov (United States)

    Ramamonjisoa, Nirilanto; Ratiney, Helene; Mutel, Elodie; Guillou, Herve; Mithieux, Gilles; Pilleul, Frank; Rajas, Fabienne; Beuf, Olivier; Cavassila, Sophie

    2013-01-01

    The assessment of liver lipid content and composition is needed in preclinical research to investigate steatosis and steatosis-related disorders. The purpose of this study was to quantify in vivo hepatic fatty acid content and composition using a method based on short echo time proton magnetic resonance spectroscopy (MRS) at 7 Tesla. A mouse model of glycogen storage disease type 1a with inducible liver-specific deletion of the glucose-6-phosphatase gene (L-G6pc−/−) mice and control mice were fed a standard diet or a high-fat/high-sucrose (HF/HS) diet for 9 months. In control mice, hepatic lipid content was found significantly higher with the HF/HS diet than with the standard diet. As expected, hepatic lipid content was already elevated in L-G6pc−/− mice fed a standard diet compared with control mice. L-G6pc−/− mice rapidly developed steatosis which was not modified by the HF/HS diet. On the standard diet, estimated amplitudes from olefinic protons were found significantly higher in L-G6pc−/− mice compared with that in control mice. L-G6pc−/− mice showed no noticeable polyunsaturation from diallylic protons. Total unsaturated fatty acid indexes measured by gas chromatography were in agreement with MRS measurements. These results showed the great potential of high magnetic field MRS to follow the diet impact and lipid alterations in mouse liver. PMID:23596325

  9. In vivo hepatic lipid quantification using MRS at 7 Tesla in a mouse model of glycogen storage disease type 1a.

    Science.gov (United States)

    Ramamonjisoa, Nirilanto; Ratiney, Helene; Mutel, Elodie; Guillou, Herve; Mithieux, Gilles; Pilleul, Frank; Rajas, Fabienne; Beuf, Olivier; Cavassila, Sophie

    2013-07-01

    The assessment of liver lipid content and composition is needed in preclinical research to investigate steatosis and steatosis-related disorders. The purpose of this study was to quantify in vivo hepatic fatty acid content and composition using a method based on short echo time proton magnetic resonance spectroscopy (MRS) at 7 Tesla. A mouse model of glycogen storage disease type 1a with inducible liver-specific deletion of the glucose-6-phosphatase gene (L-G6pc(-/-)) mice and control mice were fed a standard diet or a high-fat/high-sucrose (HF/HS) diet for 9 months. In control mice, hepatic lipid content was found significantly higher with the HF/HS diet than with the standard diet. As expected, hepatic lipid content was already elevated in L-G6pc(-/-) mice fed a standard diet compared with control mice. L-G6pc(-/-) mice rapidly developed steatosis which was not modified by the HF/HS diet. On the standard diet, estimated amplitudes from olefinic protons were found significantly higher in L-G6pc(-/-) mice compared with that in control mice. L-G6pc(-/-) mice showed no noticeable polyunsaturation from diallylic protons. Total unsaturated fatty acid indexes measured by gas chromatography were in agreement with MRS measurements. These results showed the great potential of high magnetic field MRS to follow the diet impact and lipid alterations in mouse liver.

  10. Intracellular calcium movements of boar spermatozoa during 'in vitro' capacitation and subsequent acrosome exocytosis follow a multiple-storage place, extracellular calcium-dependent model.

    Science.gov (United States)

    Yeste, M; Fernández-Novell, J M; Ramió-Lluch, L; Estrada, E; Rocha, L G; Cebrián-Pérez, J A; Muiño-Blanco, T; Concha, I I; Ramírez, A; Rodríguez-Gil, J E

    2015-07-01

    This work analysed intracellular calcium stores of boar spermatozoa subjected to 'in vitro' capacitation (IVC) and subsequent progesterone-induced acrosome exocytosis (IVAE). Intracellular calcium was analysed through two calcium markers with different physico-chemical properties, Fluo-3 and Rhod-5N. Indicative parameters of IVC and IVAE were also evaluated. Fluo-3 was located at both the midpiece and the whole head. Rhod-5N was present at the sperm head. This distribution did not change in any of the assayed conditions. Induction of IVC was concomitant with an increase in both head and midpiece Ca(2+) signals. Additionally, while IVC induction was concurrent with a significant (p spermatozoa in the absence of calcium showed a loss of both Ca(2+) labellings concomitantly with the sperm's inability to achieve IVC. The absence of extracellular calcium also induced a severe decrease in the percentage of spermatozoa exhibiting high mitochondrial membrane potential (hMMP). The IVAE was accompanied by a fast increase in both Ca(2+) signalling in control spermatozoa. These peaks were either not detected or much lessened in the absence of calcium. Remarkably, Fluo-3 marking at the midpiece increased after progesterone addition to sperm cells incubated in a medium without Ca(2+) . The simultaneous addition of progesterone with the calcium chelant EGTA inhibited IVAE, and this was accompanied by a significant (p spermatozoa present different calcium deposits with a dynamic equilibrium among them and with the extracellular environment. Additionally, the modulation role of the intracellular calcium in spermatozoa function seems to rely on its precise localization in boar spermatozoa. © 2015 American Society of Andrology and European Academy of Andrology.

  11. Peripheral leukocyte anomaly detected with routine automated hematology analyzer sensitive to adipose triglyceride lipase deficiency manifesting neutral lipid storage disease with myopathy/triglyceride deposit cardiomyovasculopathy

    Directory of Open Access Journals (Sweden)

    Akira Suzuki

    2014-01-01

    Full Text Available Adipose triglyceride lipase (ATGL deficiency manifesting neutral lipid storage disease with myopathy/triglyceride deposit cardiomyovasculopathy presents distinct fat-containing vacuoles known as Jordans' anomaly in peripheral leucocytes. To develop an automatic notification system for Jordans' anomaly in ATGL-deficient patients, we analyzed circulatory leukocyte scattergrams on automated hematology analyzer XE-5000. The BASO-WX and BASO-WY values were found to be significantly higher in patients than those in non-affected subjects. The two parameters measured by automated hematology analyzer may be expected to provide an important diagnostic clue for homozygous ATGL deficiency.

  12. Lipid-storage myopathy and respiratory insufficiency due to ETFQO mutations in a patient with late-onset multiple acyl-CoA dehydrogenation deficiency

    DEFF Research Database (Denmark)

    Olsen, R K J; Pourfarzam, M; Morris, A A M

    2004-01-01

    We report a patient with lipid-storage myopathy due to multiple acyl-CoA dehydrogenation deficiency (MADD). Molecular genetic analysis showed that she was compound heterozygous for mutations in the gene for electron transfer flavoprotein:ubiquinone oxidoreductase (ETFQO). Despite a good initial r...... response to treatment, she developed respiratory insufficiency at age 14 years and has required long-term overnight ventilation. Thus, MADD is one of the few conditions that can cause a myopathy with weakness of the respiratory muscles out of proportion to the limb muscles....

  13. Effects of Tannic Acid on Lipid and Protein Oxidation, Color, and Volatiles of Raw and Cooked Chicken Breast Meat during Storage

    Directory of Open Access Journals (Sweden)

    Marwan Al-Hijazeen

    2016-06-01

    Full Text Available The objective of this study was to determine the effect of tannic acid (TA on the oxidative stability and the quality characteristics of ground chicken breast meat. Five treatments including (1 control (none added, (2 2.5 ppm TA, (3 5 ppm TA, (4 10 ppm TA, and (5 5 ppm butylated hydroxyanisole (BHA were added to boneless, skinless ground chicken breast meat, and used for both raw and cooked meat studies. For the raw meat study, the ground chicken breast meat was packaged in oxygen-permeable bags and stored at 4 °C for 7 days. For the cooked study, raw ground meat samples were vacuum-packaged in oxygen-impermeable vacuum bags, cooked in-bag to the internal temperature of 75 °C, re-packaged in oxygen-permeable bags, and then stored. Both raw and cooked meats were analyzed for lipid and protein oxidation, color, and volatiles (cooked meat only at 0, 3, and 7 days of storage. Raw meats with 10 ppm of TA added had significantly (p ≤ 0.05 lower lipid and protein oxidation than other treatments during storage. In addition, TA at 10 ppm level maintained the highest color a*- and L*-values during storage. Cooked chicken breast meat with 5 and 10 ppm TA added produced significantly (p ≤ 0.05 lower amounts of off-odor volatiles than other treatments. Among the volatile compounds, the amount of hexanal increased rapidly during storage for cooked meat. However, meats with 5 and 10 ppm TA added showed the lowest amount of hexanal and other aldehydes related to lipid oxidation, indicating a strong antioxidant effect of TA in cooked chicken breast meat. Furthermore, the differences in aldehydes among the treatments were bigger in cooked than in raw meat, indicating that the antioxidant effect of TA in cooked meat was greater than that in raw meat. Therefore, TA at >5 ppm can be used as a good natural preservative in cooked chicken meat to maintain its quality during storage.

  14. Nonlinear microscopy of lipid storage and fibrosis in muscle and liver tissues of mice fed high-fat diets

    Science.gov (United States)

    Brackmann, Christian; Gabrielsson, Britt; Svedberg, Fredrik; Holmäng, Agneta; Sandberg, Ann-Sofie; Enejder, Annika

    2010-11-01

    Hallmarks of high-fat Western diet intake, such as excessive lipid accumulation in skeletal muscle and liver as well as liver fibrosis, are investigated in tissues from mice using nonlinear microscopy, second harmonic generation (SHG), and coherent anti-Stokes Raman scattering (CARS), supported by conventional analysis methods. Two aspects are presented; intake of standard chow versus Western diet, and a comparison between two high-fat Western diets of different polyunsaturated lipid content. CARS microscopy images of intramyocellular lipid droplets in muscle tissue show an increased amount for Western diet compared to standard diet samples. Even stronger diet impact is found for liver samples, where combined CARS and SHG microscopy visualize clear differences in lipid content and collagen fiber development, the latter indicating nonalcoholic fatty liver disease (NAFLD) and steatohepatitis induced at a relatively early stage for Western diet. Characteristic for NAFLD, the fibrous tissue-containing lipids accumulate in larger structures. This is also observed in CARS images of liver samples from two Western-type diets of different polyunsaturated lipid contents. In summary, nonlinear microscopy has strong potential (further promoted by technical advances toward clinical use) for detection and characterization of steatohepatitis already in its early stages.

  15. Improved platelet survival after cold storage by prevention of glycoprotein Ibα clustering in lipid rafts

    NARCIS (Netherlands)

    Gitz, E.; Koekman, C.A.; van den Heuvel, D.J.|info:eu-repo/dai/nl/355331861; Deckmyn, H.; Akkerman, J.W.N.; Gerritsen, H.C.|info:eu-repo/dai/nl/071548777; Urbanus, R.T

    2012-01-01

    ABSTRACT Background Room temperature storage of platelets for transfusion increases the risk of microbial infection and decreases platelet functionality, leading to out-date discard rates of up to 20%. Cold storage may be a better alternative, but this treatment leads to rapid platelet clearance

  16. Adipose subtype–selective recruitment of TLE3 or Prdm16 by PPARγ specifies lipid-storage versus thermogenic gene programs

    Science.gov (United States)

    Villanueva, Claudio J.; Vergnes, Laurent; Wang, Jiexin; Drew, Brian G.; Hong, Cynthia; Tu, Yiping; Hu, Yan; Peng, Xu; Xu, Feng; Saez, Enrique; Wroblewski, Kevin; Hevener, Andrea L.; Reue, Karen; Fong, Loren G.; Young, Stephen G.; Tontonoz, Peter

    2013-01-01

    Transcriptional effectors of white adipocyte-selective gene expression have not been described. Here we show that TLE3 is a white-selective cofactor that acts reciprocally with the brown-selective cofactor Prdm16 to specify lipid storage and thermogenic gene programs. Occupancy of TLE3 and Prdm16 on certain promoters is mutually exclusive, due to the ability of TLE3 to disrupt the physical interaction between Prdm16 and PPARγ. When expressed at elevated levels in brown fat, TLE3 counters Prdm16, suppressing brown-selective genes and inducing white-selective genes, resulting in impaired fatty acid oxidation and thermogenesis. Conversely, mice lacking TLE3 in adipose tissue show enhanced thermogenesis in inguinal white adipose depots and are protected from age-dependent deterioration of brown adipose tissue function. Our results suggest that the establishment of distinct adipocyte phenotypes with different capacities for thermogenesis and lipid storage is accomplished in part through the cell type–selective recruitment of TLE3 or Prdm16 to key adipocyte target genes. PMID:23473036

  17. Asparagine slows down the breakdown of storage lipid and degradation of autophagic bodies in sugar-starved embryo axes of germinating lupin seeds.

    Science.gov (United States)

    Borek, Sławomir; Paluch-Lubawa, Ewelina; Pukacka, Stanisława; Pietrowska-Borek, Małgorzata; Ratajczak, Lech

    2017-02-01

    The research was conducted on embryo axes of yellow lupin (Lupinus luteus L.), white lupin (Lupinus albus L.) and Andean lupin (Lupinus mutabilis Sweet), which were isolated from imbibed seeds and cultured for 96h in vitro under different conditions of carbon and nitrogen nutrition. Isolated embryo axes were fed with 60mM sucrose or were sugar-starved. The effect of 35mM asparagine (a central amino acid in the metabolism of germinating lupin seeds) and 35mM nitrate (used as an inorganic kind of nitrogen) on growth, storage lipid breakdown and autophagy was investigated. The sugar-starved isolated embryo axes contained more total lipid than axes fed with sucrose, and the content of this storage compound was even higher in sugar-starved isolated embryo axes fed with asparagine. Ultrastructural observations showed that asparagine significantly slowed down decomposition of autophagic bodies, and this allowed detailed analysis of their content. We found peroxisomes inside autophagic bodies in cells of sugar-starved Andean lupin embryo axes fed with asparagine, which led us to conclude that peroxisomes may be degraded during autophagy in sugar-starved isolated lupin embryo axes. One reason for the slower degradation of autophagic bodies was the markedly lower lipolytic activity in axes fed with asparagine. Copyright © 2016 The Author(s). Published by Elsevier GmbH.. All rights reserved.

  18. Colour, lipid and protein stability of Rhea americana meat during air- and vacuum-packaged storage: influence of muscle on oxidative processes.

    Science.gov (United States)

    Filgueras, R S; Gatellier, P; Aubry, L; Thomas, A; Bauchart, D; Durand, D; Zambiazi, R C; Santé-Lhoutellier, V

    2010-11-01

    Physicochemical characteristics and oxidative stability during storage were determined in Gastrocnemius pars interna (GN) and Iliofiburalis (IF) muscles of Rhea americana. Glycolytic potential (GP) and pH decline of muscles were measured within the first 24 h post mortem. Colour, lipid and protein stability were determined during storage of meat, i.e. 5 days under air-packaging at 4°C, or 28 days under vacuum-packaging at 4°C. In parallel, anti-oxidant status of muscles was estimated by measuring α-tocopherol content and anti-oxidant enzyme activities (superoxide dismutase and catalase), while pro-oxidant status was evaluated by determining haeminic iron and long chain fatty acids (especially polyunsaturated fatty acids). The ultimate pH was similar in both muscles, but the GP value was significantly higher in IF than in GN muscle. Haeminic iron and alpha-tocopherol content differed between muscles, with 30% more haeminic iron (psensorial analysis. Under vacuum-packaging, both muscles showed a high stability of colour and no oxidation of lipids and proteins. Copyright © 2010 The American Meat Science Association. Published by Elsevier Ltd. All rights reserved.

  19. A novel mutation in PNPLA2 causes neutral lipid storage disease with myopathy and triglyceride deposit cardiomyovasculopathy: a case report and literature review.

    Science.gov (United States)

    Kaneko, Kimihiko; Kuroda, Hiroshi; Izumi, Rumiko; Tateyama, Maki; Kato, Masaaki; Sugimura, Koichiro; Sakata, Yasuhiko; Ikeda, Yoshihiko; Hirano, Ken-Ichi; Aoki, Masashi

    2014-07-01

    Mutations in PNPLA2 cause neutral lipid storage disease with myopathy (NLSDM) or triglyceride deposit cardiomyovasculopathy (TGCV). We report a 59-year-old patient with NLSDM/TGCV presenting marked asymmetric skeletal myopathy and cardiomyovasculopathy. Skeletal muscle and endomyocardial biopsies showed cytoplasmic vacuoles containing neutral lipid. Gene analysis revealed a novel homozygous mutation (c.576delC) in PNPLA2. We reviewed 37 genetically-proven NLSDM/TGCV cases; median age was 30 years; distribution of myopathy was proximal (69%) and distal predominant (16%); asymmetric myopathy (right>left) was reported in 41% of the patients. Frequently-affected muscles were posterior compartment of leg (75%), shoulder girdle to upper arm (50%), and paraspinal (33%). Skeletal muscle biopsies showed lipid accumulation in 100% and rimmed vacuoles in 22%. Frequent comorbidities were cardiomyopathy (44%), hyperlipidemia (23%), diabetes mellitus (24%), and pancreatitis (14%). PNPLA2 mutations concentrated in Exon 4-7 without apparent genotype-phenotype correlations. To know the characteristic features is essential for the early diagnosis of NLSDM/TGCV. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Fatty acid composition in fractions of structural and storage lipids in liver and skeletal muscle of hereditary hypertriglyceridemic rats.

    Science.gov (United States)

    Bohov, P; Seböková, E; Gasperíková, D; Langer, P; Klimes, I

    1997-09-20

    The fatty acid (FA) compositions of liver and skeletal muscle structural lipids, overall phospholipids and phosphatidylcholine, and triglycerides (TG) were determined in the hereditary hypertriglyceridemic (HTG) rat, a nonobese animal model of the insulin resistance syndrome. Four groups of HTG rats and four groups of control animals were fed equal-energy diets for two weeks: basal (B), high-sucrose (HS), or fish oil-supplemented basal (BFO) or high-sucrose (HSFO) diets. In the liver of HTG rats, a decrease of n-6 long-chain polyunsaturated FA (PUFA), especially in 20:4n-6, in comparison with controls was found. Moreover, a concomitant accumulation of 18:2n-6 in structural lipids was observed. These differences were more pronounced in liver than in skeletal muscle. HS feeding raised the proportion of 18:1n-9 and decreased 18:2n-6 in lipid fractions. In both tissues and in both strains, the amounts of long-chain n-3 PUFA, as well as the level of total C20-22 PUFA, went up after fish oil feeding. However, the effects were somewhat less pronounced in the HTG rats. The increase in n-3 PUFA occurred mainly at the expense of reduced levels of 18:2n-6 in structural lipids and of 18:1n-9 in triglycerides. These changes were associated, in companion studies reported in this volume, with improved insulin action in HTG rats. In conclusion, the FA composition in lipid subclasses of HTG rats differs significantly from the controls mainly in liver structural lipids, suggesting the impairment of PUFA desaturation. Dietary change effected a similar modulation of FA profile across both strains, with fish oil increasing the levels of long-chain PUFA toward control values in the NTG rats. The HTG rat thus provides an interesting animal model for the study of impaired fatty acid metabolism.

  1. Maturity and storage influence on the apple (Malus domestica) allergen Mal d 3, a nonspecific lipid transfer protein

    NARCIS (Netherlands)

    Sancho, Ana I.; Foxall, Robert; Rigby, Neil M.; Browne, Thomas; Zuidmeer, Laurian; van Ree, Ronald; Waldron, Keith W.; Mills, E. N. Clare

    2006-01-01

    Consumption of apples can provoke severe allergic reactions, in susceptible individuals, due to the presence of the allergen Mal d 3, a nonspecific lipid transfer protein, found largely in the fruit skin. Levels of Mal d 3 were determined in peel as a function of apple cultivar, position of the

  2. Effects of dietary vanadium on growth and lipid storage in a larval anuran: Results from studies employing ad libitum and rationed feeding

    Energy Technology Data Exchange (ETDEWEB)

    Rowe, Christopher L. [University of Maryland Center for Environmental Science, Chesapeake Biological Laboratory, P.O. Box 38, Solomons, MD 20688 (United States)], E-mail: Rowe@cbl.umces.edu; Heyes, Andrew [University of Maryland Center for Environmental Science, Chesapeake Biological Laboratory, P.O. Box 38, Solomons, MD 20688 (United States); Hopkins, William [Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, 100 Cheatham Hall, Blacksburg, VA 24061 (United States)

    2009-01-31

    Vanadium (V) exerts a variety of effects related to metabolic function in vertebrates, including modifying glycolytic pathways and lipid metabolism. However, little is known about toxicity of V to wildlife in natural systems. We conducted parallel, independent studies to evaluate the effect of dietary exposure to vanadium on survival, metabolism, growth, and lipid storage of larval leopard frogs (Rana sphenocephala). In one study ('Ad lib') larvae were fed unlimited food and in the other ('Ration') larvae were fed a restricted diet. Experimental diets contained 10 ppm dw V{sub total} (Control, 'C'), 109 ppm (Low, 'L'), and 363 ppm (High, 'H'). In neither study did V affect metabolic rate or survival to forelimb emergence. However, in the Ration study, 31% of individuals in H that had initiated metamorphosis died prior to completion of metamorphosis, compared with 22% in M and 9% in C, however the difference was not significant at {alpha} = 0.05. Mortality during metamorphosis in the Ad lib study was more variable, yet followed a similar trend (26, 14, and 12% mortality in H, L, and C). In both studies, individuals that died during the metamorphic period were smaller at the time of forelimb emergence than those that survived. In the Ration study, individuals in H also had significantly lower growth rates, delayed metamorphosis, and reduced lipid content at metamorphosis compared to C and L. Growth was not affected by V in the Ad lib study. Our results suggest that habitat contamination by V may present risks to amphibians during the metamorphic period attributable to energetic responses influencing size at the initiation of metamorphosis and body lipid stores. Furthermore, while we cannot make formal comparisons between the studies, our results imply that protocols that employ ad libitum feeding regimes could fail to capture the effects of contaminants as they may be expressed in natural situations in which resources

  3. 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...... 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...... in ether lipid metabolism and intracellular ether lipid trafficking....

  4. Antioxidative Effect of Seaweed Extracts in Chilled Storage of Minced Atlantic Mackerel (Scomber scombrus): Effect on Lipid and Protein Oxidation

    DEFF Research Database (Denmark)

    Babakhani, Aria; Farvin, K. H Sabeena; Jacobsen, Charlotte

    2016-01-01

    In this study, antioxidant activity of absolute ethanol, 50 % ethanol and water extracts of two species of seaweeds namely, Fucus serratus and Polysiphonia fucoides were evaluated for their ability to retard lipid and protein oxidation in minced mackerel. Mackerel mince added with 0.5 g...... mackerel. Water extract with lowest phenolic content showed no antioxidant effect in minced mackerel. In conclusion, the 50 % ethanolic extracts of P. fucoides can be a potential source of natural antioxidants, as these extracts have antioxidant activities similar to synthetic antioxidants such as BHT....../kg of extracts was prepared. For comparison, BHT at 0.2 g/kg and a control with no added extracts were also prepared. The samples were stored at 5 °C for 8 days, and sampling was done at time 0, 1, 2, 4, 5 and 8 days. The 50 % ethanolic extracts of P. fucoides were found to be very effective in retarding lipid...

  5. Intracellular transport: from physics to ... biology.

    Science.gov (United States)

    Roux, Aurélien; Cuvelier, Damien; Bassereau, Patricia; Goud, Bruno

    2008-03-01

    Considerable effort over the past three decades has allowed the identification of the protein families that control the cellular machinery responsible for intracellular transport within eukaryotic cells. These proteins are estimated to represent about 10-20% of the human "proteome." The complexity of intracellular transport makes useful the development of model membranes. We describe here experimental systems based on lipid giant unilamellar vesicles (GUVs), which are attached to kinesin molecules. These systems give rise to thin membrane tubes and to complex tubular networks when incubated in vitro with microtubules and ATP. This type of assay, which mimics key events occurring during intracellular transport, allows physicists and biologists to understand how the unique mechanical properties of lipid membranes could be involved in the budding process, the sorting of cargo proteins and lipids, and the separation of the buds from a donor membrane.

  6. A Molecular Probe for the Detection of Polar Lipids in Live Cells.

    Directory of Open Access Journals (Sweden)

    Christie A Bader

    Full Text Available Lipids have an important role in many aspects of cell biology, including membrane architecture/compartment formation, intracellular traffic, signalling, hormone regulation, inflammation, energy storage and metabolism. Lipid biology is therefore integrally involved in major human diseases, including metabolic disorders, neurodegenerative diseases, obesity, heart disease, immune disorders and cancers, which commonly display altered lipid transport and metabolism. However, the investigation of these important cellular processes has been limited by the availability of specific tools to visualise lipids in live cells. Here we describe the potential for ReZolve-L1™ to localise to intracellular compartments containing polar lipids, such as for example sphingomyelin and phosphatidylethanolamine. In live Drosophila fat body tissue from third instar larvae, ReZolve-L1™ interacted mainly with lipid droplets, including the core region of these organelles. The presence of polar lipids in the core of these lipid droplets was confirmed by Raman mapping and while this was consistent with the distribution of ReZolve-L1™ it did not exclude that the molecular probe might be detecting other lipid species. In response to complete starvation conditions, ReZolve-L1™ was detected mainly in Atg8-GFP autophagic compartments, and showed reduced staining in the lipid droplets of fat body cells. The induction of autophagy by Tor inhibition also increased ReZolve-L1™ detection in autophagic compartments, whereas Atg9 knock down impaired autophagosome formation and altered the distribution of ReZolve-L1™. Finally, during Drosophila metamorphosis fat body tissues showed increased ReZolve-L1™ staining in autophagic compartments at two hours post puparium formation, when compared to earlier developmental time points. We concluded that ReZolve-L1™ is a new live cell imaging tool, which can be used as an imaging reagent for the detection of polar lipids in

  7. A Molecular Probe for the Detection of Polar Lipids in Live Cells.

    Science.gov (United States)

    Bader, Christie A; Shandala, Tetyana; Carter, Elizabeth A; Ivask, Angela; Guinan, Taryn; Hickey, Shane M; Werrett, Melissa V; Wright, Phillip J; Simpson, Peter V; Stagni, Stefano; Voelcker, Nicolas H; Lay, Peter A; Massi, Massimiliano; Plush, Sally E; Brooks, Douglas A

    2016-01-01

    Lipids have an important role in many aspects of cell biology, including membrane architecture/compartment formation, intracellular traffic, signalling, hormone regulation, inflammation, energy storage and metabolism. Lipid biology is therefore integrally involved in major human diseases, including metabolic disorders, neurodegenerative diseases, obesity, heart disease, immune disorders and cancers, which commonly display altered lipid transport and metabolism. However, the investigation of these important cellular processes has been limited by the availability of specific tools to visualise lipids in live cells. Here we describe the potential for ReZolve-L1™ to localise to intracellular compartments containing polar lipids, such as for example sphingomyelin and phosphatidylethanolamine. In live Drosophila fat body tissue from third instar larvae, ReZolve-L1™ interacted mainly with lipid droplets, including the core region of these organelles. The presence of polar lipids in the core of these lipid droplets was confirmed by Raman mapping and while this was consistent with the distribution of ReZolve-L1™ it did not exclude that the molecular probe might be detecting other lipid species. In response to complete starvation conditions, ReZolve-L1™ was detected mainly in Atg8-GFP autophagic compartments, and showed reduced staining in the lipid droplets of fat body cells. The induction of autophagy by Tor inhibition also increased ReZolve-L1™ detection in autophagic compartments, whereas Atg9 knock down impaired autophagosome formation and altered the distribution of ReZolve-L1™. Finally, during Drosophila metamorphosis fat body tissues showed increased ReZolve-L1™ staining in autophagic compartments at two hours post puparium formation, when compared to earlier developmental time points. We concluded that ReZolve-L1™ is a new live cell imaging tool, which can be used as an imaging reagent for the detection of polar lipids in different intracellular

  8. A Molecular Probe for the Detection of Polar Lipids in Live Cells

    Science.gov (United States)

    Bader, Christie A.; Shandala, Tetyana; Carter, Elizabeth A.; Ivask, Angela; Guinan, Taryn; Hickey, Shane M.; Werrett, Melissa V.; Wright, Phillip J.; Simpson, Peter V.; Stagni, Stefano; Voelcker, Nicolas H.; Lay, Peter A.; Massi, Massimiliano; Brooks, Douglas A.

    2016-01-01

    Lipids have an important role in many aspects of cell biology, including membrane architecture/compartment formation, intracellular traffic, signalling, hormone regulation, inflammation, energy storage and metabolism. Lipid biology is therefore integrally involved in major human diseases, including metabolic disorders, neurodegenerative diseases, obesity, heart disease, immune disorders and cancers, which commonly display altered lipid transport and metabolism. However, the investigation of these important cellular processes has been limited by the availability of specific tools to visualise lipids in live cells. Here we describe the potential for ReZolve-L1™ to localise to intracellular compartments containing polar lipids, such as for example sphingomyelin and phosphatidylethanolamine. In live Drosophila fat body tissue from third instar larvae, ReZolve-L1™ interacted mainly with lipid droplets, including the core region of these organelles. The presence of polar lipids in the core of these lipid droplets was confirmed by Raman mapping and while this was consistent with the distribution of ReZolve-L1™ it did not exclude that the molecular probe might be detecting other lipid species. In response to complete starvation conditions, ReZolve-L1™ was detected mainly in Atg8-GFP autophagic compartments, and showed reduced staining in the lipid droplets of fat body cells. The induction of autophagy by Tor inhibition also increased ReZolve-L1™ detection in autophagic compartments, whereas Atg9 knock down impaired autophagosome formation and altered the distribution of ReZolve-L1™. Finally, during Drosophila metamorphosis fat body tissues showed increased ReZolve-L1™ staining in autophagic compartments at two hours post puparium formation, when compared to earlier developmental time points. We concluded that ReZolve-L1™ is a new live cell imaging tool, which can be used as an imaging reagent for the detection of polar lipids in different intracellular

  9. Modification of Lipid Profile in Commercial Cow Milk Samples before and after Their Expiration Date: Evaluation of Storage Crucial Parameters and Possible Environmentally Friendly Disposal Alternatives

    Directory of Open Access Journals (Sweden)

    Eduardo Sommella

    2018-01-01

    Full Text Available Milk waste is considered a highly polluting material and its disposal is an economic and environmental problem for the dairy sector. Despite this, it can be turned into a source of nutraceutical products and biodiesel substrate. The objective of this study was to determine the qualitative and quantitative variation of single fatty acids in cow milk samples before expiration date and within 28 days after expiration date in order to monitor how the profile of the lipid fraction is influenced by different physicochemical parameters. It was shown that lipolysis in milk is a process independent of time but dependent on the values of pH and total titratable acidity, while crucial parameters for the lipid oxidation are temperature and time of exposure to atmospheric oxygen. All of these factors are at the basis of the efficacy of milk storage conditions. Moreover, our data demonstrate that milk, several weeks after its expiry date, is a rich source of fatty acids that may be recovered as potential substrates for the formulation of economically viable products and eco-friendly diesel-like fuels.

  10. Assessment of the Indicators Atherogenic Index and Lipid Preventive Score of White Brine Cheese by Buffalo Milk after Technological Processing and Storage

    International Nuclear Information System (INIS)

    Ivanova, S.; Nacheva, I.; Miteva, D.

    2011-01-01

    The present investigation had the objective to study the changes in the atherogenic index - AI and the lipid preventive score - LPS as nutritious indicators for assessment of the risk of cardio-vascular diseases, on the basis of the fatty acid composition of white brine cheese by buffalo milk after applying of two methods of preservation – freeze-drying and dry gamma sterilization with 2 and 4 kGy. The analysis was made with the aid of gas chromatograph SHIMADZU 2010. The lyophilized cheese is characterized by a comparatively low AI - 2.59 after lyophilization and is preserved during storage - 2.55. After lyophilization the LPS of the cheese was the highest – 103.70, while after irradiation a decrease of its value was observed up to 97.73 with 2 kGy and 96.91 with 4 kGy. Key words: white brine cheese by buffalo milk, atherogenic index, lipid preventive score, freeze-drying - lyophilization, gamma sterilization

  11. Assessment of the indicators atherogenic index and lipid preventive score of white brine cheese by buffalo milk after technological processing and storage

    International Nuclear Information System (INIS)

    Ivanova, S.; Nacheva, I.; Miteva, D.

    2011-01-01

    The present investigation had the objective to study the changes in the atherogenic index - AI and the lipid preventive score - LPS as nutritious indicators for assessment of the risk of cardio-vascular diseases, on the basis of the fatty acid composition of white brine cheese by buffalo milk after applying of two methods of preservation – freeze-drying and dry gamma sterilization with 2 and 4 kGy. The analysis was made with the aid of gas chromatograph SHIMADZU 2010. The lyophilized cheese is characterized by a comparatively low AI - 2.59 after lyophilization and is preserved during storage - 2.55. After lyophilization the LPS of the cheese was the highest – 103.70, while after irradiation a decrease of its value was observed up to 97.73 with 2 kGy and 96.91 with 4 kGy. Key words: white brine cheese by buffalo milk, atherogenic index, lipid preventive score, freeze-drying - lyophilization, gamma sterilization

  12. Fatty Acid Uptake and Lipid Storage Induced by HIF-1α Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation

    Directory of Open Access Journals (Sweden)

    Karim Bensaad

    2014-10-01

    Full Text Available Summary: An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3 and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1α (HIF-1α-dependent manner. There was a significant lipid droplet (LD accumulation in hypoxia that was time and O2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via β-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo. : Bensaad et al. now show that FABP3 and FABP7 are induced by HIF-1α and lead to a significant lipid droplet (LD accumulation in hypoxia. In hypoxia-reoxygenation, ATP production occurs via fatty acid β-oxidation or glycogen degradation in a cell-type-dependent manner, while inhibition of LD formation increases ROS toxicity and decreases cell survival in vitro and strongly impairs tumorigenesis in vivo.

  13. Seasonal changes in the composition of storage and membrane lipids in overwintering larvae of the codling moth, Cydia pomonella.

    Science.gov (United States)

    Rozsypal, Jan; Koštál, Vladimír; Berková, Petra; Zahradníčková, Helena; Simek, Petr

    2014-10-01

    The codling moth (Cydia pomonella) is a major insect pest of apples worldwide. It overwinters as a diapausing fifth instar larva. The overwintering is often a critical part of the insect life-cycle in temperate zone. This study brings detailed analysis of seasonal changes in lipid composition and fluidity in overwintering larvae sampled in the field. Fatty acid composition of triacylglycerol (TG) depots in the fat body and relative proportions of phospholipid (PL) molecular species in biological membranes were analyzed. In addition, temperature of melting (Tm) in TG depots was assessed by using differential scanning calorimetry and the conformational order (fluidity) of PL membranes was analyzed by measuring the anisotropy of fluorescence polarization of diphenylhexatriene probe in membrane vesicles. We observed a significant increase of relative proportion of linoleic acid (C18:2n6) at the expense of palmitic acid (C16:0) in TG depots during the larval transition to diapause accompanied with decreasing melting temperature of total lipids, which might increase the accessibility of depot fats for enzymatic breakdown during overwintering. The fluidity of membranes was maintained very high irrespective of developmental mode or seasonally changing acclimation status of larvae. The seasonal changes in PL composition were relatively small. We discuss these results in light of alternative survival strategies of codling moth larvae (supercooling vs. freezing), variability and low predictability of environmental conditions, and other cold tolerance mechanisms such as extending the supercooling capacity and massive accumulation of cryoprotective metabolites. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Evaluation of food grade solvents for lipid extraction and impact of storage temperature on fatty acid composition of edible seaweeds Laminaria digitata (Phaeophyceae) and Palmaria palmata (Rhodophyta).

    Science.gov (United States)

    Schmid, Matthias; Guihéneuf, Freddy; Stengel, Dagmar B

    2016-10-01

    This study evaluated the impact of different food- and non-food grade extraction solvents on yield and fatty acid composition of the lipid extracts of two seaweed species (Palmaria palmata and Laminaria digitata). The application of chloroform/methanol and three different food grade solvents (ethanol, hexane, ethanol/hexane) revealed significant differences in both, extraction yield and fatty acid composition. The extraction efficiency, in terms of yields of total fatty acids (TFA), was in the order: chloroform/methanol>ethanol>hexane>ethanol/hexane for both species. Highest levels of polyunsaturated fatty acids (PUFA) were achieved by the extraction with ethanol. Additionally the effect of storage temperature on the stability of PUFA in ground and freeze-dried seaweed biomass was investigated. Seaweed samples were stored for a total duration of 22months at three different temperatures (-20°C, 4°C and 20°C). Levels of TFA and PUFA were only stable after storage at -20°C for the two seaweed species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Effects of plant polyphenols and a-tocopherol on lipid oxidation, residual nitrites, biogenic amines, and N-nitrosamines formation during ripening and storage of dry-cured bacon

    Science.gov (United States)

    Effects of plant polyphenols (green tea polyphenols (GTP) and grape seed extract (GSE) and a-tocopherol on physicochemical parameters, lipid oxidation, residual nitrite, microbiological counts, biogenic amines, and N-nitrosamines were determined in bacons during dry-curing and storage. Results show ...

  16. Intracellular sphingosine releases calcium from lysosomes

    Science.gov (United States)

    Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

    2015-01-01

    To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC. DOI: http://dx.doi.org/10.7554/eLife.10616.001 PMID:26613410

  17. 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...

  18. Defining Lipid Transport Pathways in Animal Cells

    Science.gov (United States)

    Pagano, Richard E.; Sleight, Richard G.

    1985-09-01

    A new technique for studying the metabolism and intracellular transport of lipid molecules in living cells based on the use of fluorescent lipid analogs is described. The cellular processing of various intermediates (phosphatidic acid and ceramide) and end products (phosphatidylcholine and phosphatidylethanolamine) in lipid biosynthesis is reviewed and a working model for compartmentalization during lipid biosynthesis is presented.

  19. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

    Directory of Open Access Journals (Sweden)

    Karen B. Kelly

    2016-09-01

    Full Text Available Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA intake compared to adequate folic acid (AFA intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF diet or 60% energy high fat (HF diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05. Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA fed rats (p < 0.05. In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.

  20. Diapause induces remodeling of the fatty acid composition of membrane and storage lipids in overwintering larvae of Ostrinia nubilalis, Hubn. (Lepidoptera: Crambidae).

    Science.gov (United States)

    Vukašinović, Elvira L; Pond, David W; Worland, M Roger; Kojić, Danijela; Purać, Jelena; Popović, Željko D; Grubor-Lajšić, Gordana

    2015-06-01

    Seasonal changes in the FA composition of triacylglycerols and phospholipids prepared from the whole bodies of non-diapausing and diapausing fifth instar larvae of Ostrinia nubilalis, Hubn. (Lepidoptera: Crambidae) were determined to evaluate the role of these lipids in diapause. Substantial changes in the FA composition of triacylglycerols and phospholipids were triggered by diapause development. This led to a significant increase in the overall FA unsaturation (UFAs/SFAs ratio), attributable to an increase in the relative proportion of MUFAs and the concomitant decrease in PUFAs and SFAs. In triacylglycerols, the significant changes in the FAs composition are the result of an increase in the relative proportions of MUFAs, palmitoleic acid (16:1n-7) and oleic acid (18:1n-9), and a concomitant reduction in the composition of SFAs and PUFAs, mainly palmitic acid (16:0) and linoleic acid (18:2n-6), respectively. Changes in the composition of phospholipids were more subtle with FAs contributing to the overall increase of FA unsaturation. Differential scanning calorimetry (DSC) analysis revealed that the melt transition temperatures of total lipids prepared from whole larvae, primarily attributable to the triacylglycerol component, were significantly lower during the time course of diapause compared with non-diapause. These observations were correlated to the FA composition of triacylglycerols, most likely enabling them to remain functional during colder winter conditions. We conclude that O. nubilalis undergoes remodeling of FA profiles of both energy storage triacylglycerols and membrane phospholipids as an element of its overwintering physiology which may improve the ability to cold harden during diapause. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Novel missense mutations in PNPLA2 causing late onset and clinical heterogeneity of neutral lipid storage disease with myopathy in three siblings.

    Science.gov (United States)

    Missaglia, Sara; Tasca, Elisabetta; Angelini, Corrado; Moro, Laura; Tavian, Daniela

    2015-01-01

    Neutral lipid storage disease with myopathy (NLSD-M) is a rare autosomal recessive disorder characterised by an abnormal accumulation of triacylglycerol into cytoplasmic lipid droplets (LDs). NLSD-M patients are mainly affected by progressive myopathy, cardiomyopathy and hepatomegaly. Mutations in the PNPLA2 gene cause variable phenotypes of NLSD-M. PNPLA2 codes for adipose triglyceride lipase (ATGL), an enzyme that hydrolyses fatty acids from triacylglycerol. This report outlines the clinical and genetic findings in a NLSD-M Italian family with three affected members. In our patients, we identified two novel PNPLA2 missense mutations (p.L56R and p.I193F). Functional data analysis demonstrated that these mutations caused the production of ATGL proteins able to bind to LDs, but with decreased lipase activity. The oldest brother, at the age of 38, had weakness and atrophy of the right upper arm and kyphosis. Now he is 61 years old and is unable to raise arms in the horizontal position. The second brother, from the age of 44, had exercise intolerance, cramps and pain in lower limbs. He is currently 50 years old and has an asymmetric distal amyotrophy. One of the two sisters, 58 years old, presents the same PNPLA2 mutations, but she is still oligo-symptomatic on neuromuscular examination with slight triceps muscle involvement. She suffered from diabetes and liver steatosis. This NLSD-M family shows a wide range of intra-familial phenotypic variability in subjects carrying the same mutations, both in terms of target-organs and in terms of rate of disease progression. Copyright © 2015. Published by Elsevier Inc.

  2. Metabolic consequences of adipose triglyceride lipase deficiency in humans: an in vivo study in patients with neutral lipid storage disease with myopathy.

    Science.gov (United States)

    Natali, Andrea; Gastaldelli, Amalia; Camastra, Stefania; Baldi, Simona; Quagliarini, Fabiana; Minicocci, Ilenia; Bruno, Claudio; Pennisi, Elena; Arca, Marcello

    2013-09-01

    The role of adipose triglyceride lipase (ATGL) in intermediate substrates metabolism has not been fully elucidated in humans. Our objective was to evaluate the consequences of ATGL deficiency on body fat distribution, insulin sensitivity, fatty acids metabolism, and energy substrate utilization. Body composition and organ fat content were measured by bioimpedance and (1)H nuclear magnetic resonance spectroscopy; heart glucose metabolism by [(18)F]deoxyglucose positron emission tomography and insulin sensitivity and β-cell function by oral glucose tolerance and 2-step euglycemic-hyperinsulinemic clamp. Lipolysis ([(2)H5]glycerol turnover) and indirect calorimetry were evaluated at fasting, after oral glucose load, during the clamp, and also during an iv epinephrine infusion. These metabolic investigations were carried out during hospitalization. Three patients affected by neutral lipid storage disease with myopathy (NLSDM) due to homozygosity for loss-of-function mutations in the ATGL gene and 6 sex-, age-, and body mass index-matched controls were studied. As expected, NLSDM patients showed diffuse, although heterogeneous, fat infiltration in skeletal muscles associated with increased visceral fat. Although heart and liver were variably affected, fat content in the pancreas was increased in all patients. Compared with healthy controls, NLSDM patients showed impaired insulin response to glucose possibly related to the severe pancreatic steatosis, preserved whole-body insulin sensitivity, and a shift toward glucose metabolism in the heart. Fasting nonesterified fatty acid concentrations as well as basal lipolytic rates and the antilipolytic effect of insulin were normal in NLSDM patients, whereas the lipolytic effect of norepinephrine was impaired. Finally, no significant abnormality in the respiratory quotient was noted in NLSDM patients. In humans, ATGL has a remarkable effect on cellular lipid droplet handling, and its lack causes both perivisceral, skeletal

  3. Effect of supplementation of the laying hen diet with olive leaves (Olea europea L.) on lipid oxidation and fatty acid profile of α-linolenic acid enriched eggs during storage.

    Science.gov (United States)

    Botsoglou, E; Govaris, A; Fletouris, D; Botsoglou, N

    2012-01-01

    1. The aim of this study was to evaluate the effect of supplementation of the layer diet with olive leaves (Olea europea L.) on lipid oxidation and fatty acid profile of α-linolenic acid enriched eggs during refrigerated storage, and to compare this effect with α-tocopheryl acetate supplementation. 2. A total of 72 brown Lohmann laying hens, equally allocated to 3 groups, were fed on diets supplemented with 40 g/kg linseed oil, or linseed oil and olive leaves at 10 g/kg or linseed oil and α-tocopheryl acetate at 200 mg/kg. Collected eggs were analysed for fatty acid profile and lipid oxidation either fresh or following 60 d storage at 4°C. 3. Results showed that olive leaves or α-tocopheryl acetate supplementation reduced lipid hydroperoxide concentration in fresh eggs but had no effect on their fatty acid profile and malondialdehyde (MDA) content compared to controls. 4. Refrigerated storage for 60 d decreased the proportions of PUFAs but increased those of MUFAs in eggs from the control diet, whilst it had no effect on the fatty acid composition of eggs from the diets supplemented with olive leaves or α-tocopheryl acetate, which in turn showed decreased concentrations of lipid hydroperoxides and MDA.

  4. Effects of Pro-Oxidants and Antioxidants on the Total Antioxidant Capacity and Lipid Oxidation Products of Milk During Refrigerated Storage.

    Science.gov (United States)

    Gutierrez, Angelica M; Boylston, Terri D; Clark, Stephanie

    2018-02-01

    Oxidized flavor is a major problem that affects the dairy industry because of its adverse effect on milk acceptability. The objectives of this research were to examine the roles of pro-oxidants and antioxidants on the oxidative stability of whole milk. In the 1st experiment, the effect of light (2300 Lux) and/or cupric sulfate (0, 0.5, and 1.0 mg/kg) as pro-oxidants in milk were investigated during an 11-d refrigerated storage period. The effects of added retinyl palmitate (1.16 mg/L; 2113 IU Vitamin A/L) and tocopheryl acetate (100 mg/kg milk fat; 5.02 IU Vitamin E/L) as antioxidants in the presence of light (2300 Lux) and light with cupric sulfate (0.05 mg/kg) during a 7-d study were investigated in the 2nd experiment. The presence of pro-oxidants significantly (P products in milk during storage. Light had a greater effect in the decrease of TAC, although cupric sulfate in the presence of light significantly increased the formation of lipid oxidation products. The addition of antioxidants resulted in a significant (P products by instrumental and sensory methods showed that the presence of light and cupric sulfate significantly (P 0.05) difference in oxidized flavor intensity was detected between milk with and without added antioxidants. Production and processing variables can affect the content of pro-oxidants and antioxidants in milk, which has an impact on flavor. An understanding of the role of these components in contributing to or minimizing off-flavor formation in milk, will help dairy producers to provide quality products to consumers. © 2017 Institute of Food Technologists®.

  5. Applications of lipid nanoparticles in gene therapy.

    Science.gov (United States)

    Del Pozo-Rodríguez, Ana; Solinís, María Ángeles; Rodríguez-Gascón, Alicia

    2016-12-01

    Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been recognized, among the large number of non-viral vectors for gene transfection, as an effective and safety alternative to potentially treat both genetic and not genetic diseases. A key feature is the possibility to be designed to overcome the numerous challenges for successful gene delivery. Lipid nanoparticles (LNs) are able to overcome the main biological barriers for cell transfection, including degradation by nucleases, cell internalization intracellular trafficking, and selectively targeting to a specific cell type. Additionally, they present important advantages: from a safety point of view LNs are prepared with well tolerated components, and from a technological point of view, they can be easily produced at large-scale, can be subjected to sterilization and lyophilization, and have shown good storage stability. This review focuses on the potential of SLNs and NLCs for gene therapy, including the main advances in their application for the treatment of ocular diseases, infectious diseases, lysosomal storage disorders and cancer, and current research for their future clinical application. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. 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.

  7. Analysis of metabolic flux phenotypes for two Arabidopsis mutants with severe impairment in seed storage lipid synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Lonien, J.; Schwender, J.

    2009-11-01

    Major storage reserves of Arabidopsis (Arabidopsis thaliana) seeds are triacylglycerols (seed oils) and proteins. Seed oil content is severely reduced for the regulatory mutant wrinkled1 (wri1-1; At3g54320) and for a double mutant in two isoforms of plastidic pyruvate kinase (pkp{beta}{sub 1}pkp{alpha}; At5g52920 and At3g22960). Both already biochemically well-characterized mutants were now studied by {sup 13}C metabolic flux analysis of cultured developing embryos based on comparison with their respective genetic wild-type backgrounds. For both mutations, in seeds as well as in cultured embryos, the oil fraction was strongly reduced while the fractions of proteins and free metabolites increased. Flux analysis in cultured embryos revealed changes in nutrient uptakes and fluxes into biomass as well as an increase in tricarboxylic acid cycle activity for both mutations. While in both wild types plastidic pyruvate kinase (PK{sub p}) provides most of the pyruvate for plastidic fatty acid synthesis, the flux through PK{sub p} is reduced in pkp{beta}{sub 1}pkp{alpha} by 43% of the wild-type value. In wri1-1, PK{sub p} flux is even more reduced (by 82%), although the genes PKp{beta}{sub 1} and PKp{alpha} are still expressed. Along a common paradigm of metabolic control theory, it is hypothesized that a large reduction in PK{sub p} enzyme activity in pkp{beta}{sub 1}pkp{alpha} has less effect on PK{sub p} flux than multiple smaller reductions in glycolytic enzymes in wri1-1. In addition, only in the wri1-1 mutant is the large reduction in PK{sub p} flux compensated in part by an increased import of cytosolic pyruvate and by plastidic malic enzyme. No such limited compensatory bypass could be observed in pkp{beta}{sub 1}pkp{alpha}.

  8. A guanine nucleotide exchange factor for Rab5 proteins is essential for intracellular transport of the proglutelin from the Golgi apparatus to the protein storage vacuole in rice endosperm.

    Science.gov (United States)

    Fukuda, Masako; Wen, Liuying; Satoh-Cruz, Mio; Kawagoe, Yasushi; Nagamura, Yoshiaki; Okita, Thomas W; Washida, Haruhiko; Sugino, Aya; Ishino, Sonoko; Ishino, Yoshizumi; Ogawa, Masahiro; Sunada, Mariko; Ueda, Takashi; Kumamaru, Toshihiro

    2013-06-01

    Rice (Oryza sativa) glutelins are synthesized on the endoplasmic reticulum as a precursor, which are then transported via the Golgi to protein storage vacuoles (PSVs), where they are proteolytically processed into acidic and basic subunits. The glutelin precursor mutant6 (glup6) accumulates abnormally large amounts of proglutelin. Map-base cloning studies showed that glup6 was a loss-of-function mutant of guanine nucleotide exchange factor (GEF), which activates Rab GTPase, a key regulator of membrane trafficking. Immunofluorescence studies showed that the transport of proglutelins and α-globulins to PSV was disrupted in glup6 endosperm. Secreted granules of glutelin and α-globulin were readily observed in young glup6 endosperm, followed by the formation of large dilated paramural bodies (PMBs) containing both proteins as the endosperm matures. The PMBs also contained membrane biomarkers for the Golgi and prevacuolar compartment as well as the cell wall component, β-glucan. Direct evidence was gathered showing that GLUP6/GEF activated in vitro GLUP4/Rab5 as well as several Arabidopsis (Arabidopsis thaliana) Rab5 isoforms to the GTP-bound form. Therefore, loss-of-function mutations in GEF or Rab5 disrupt the normal transport of proglutelin from the Golgi to PSVs, resulting in the initial extracellular secretion of these proteins followed, in turn, by the formation of PMBs. Overall, our results indicate that GLUP6/GEF is the activator of Rab5 GTPase and that the cycling of GTP- and GDP-bound forms of this regulatory protein is essential for the intracellular transport of proglutelin and α-globulin from the Golgi to PSVs and in the maintenance of the general structural organization of the endomembrane system in rice seeds.

  9. Late onset of neutral lipid storage disease due to novel PNPLA2 mutations causing total loss of lipase activity in a patient with myopathy and slight cardiac involvement.

    Science.gov (United States)

    Missaglia, Sara; Maggi, Lorenzo; Mora, Marina; Gibertini, Sara; Blasevich, Flavia; Agostoni, Piergiuseppe; Moro, Laura; Cassandrini, Denise; Santorelli, Filippo Maria; Gerevini, Simonetta; Tavian, Daniela

    2017-05-01

    Neutral lipid storage disease with myopathy (NLSDM) presents with skeletal muscle myopathy and severe dilated cardiomyopathy in nearly 40% of cases. NLSDM is caused by mutations in the PNPLA2 gene, which encodes the adipose triglyceride lipase (ATGL). Here we report clinical and genetic findings of a patient carrying two novel PNPLA2 mutations (c.696+4A>G and c.553_565delGTCCCCCTTCTCG). She presented at age 39 with right upper limb abduction weakness slowly progressing over the years with asymmetric involvement of proximal upper and lower limb muscles. Cardiological evaluation through ECG and heart echo scan was normal until the age 53, when mild left ventricular diastolic dysfunction was detected. Molecular analysis revealed that only one type of PNPLA2 transcript, with exon 5 skipping, was expressed in patient cells. Such aberrant mRNA causes the production of a shorter ATGL protein, lacking part of the catalytic domain. This is an intriguing case, displaying severe PNPLA2 mutations with clinical presentation characterized by slight cardiac impairment and full expression of severe asymmetric myopathy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins

    NARCIS (Netherlands)

    Neumann, S.

    2008-01-01

    Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins In this thesis, I studied the intra- and intercellular transport of lipidic molecules, in particular glycosphingolipids and lipid-modified proteins. The first part focuses on the intracellular transport of

  11. Expression, purification, crystallization and structure of human adipocyte lipid-binding protein (aP2)

    International Nuclear Information System (INIS)

    Marr, Eric; Tardie, Mark; Carty, Maynard; Brown Phillips, Tracy; Wang, Ing-Kae; Soeller, Walt; Qiu, Xiayang; Karam, George

    2006-01-01

    The crystal structure of human adipocyte lipid-binding protein (aP2) with a bound palmitate is reported at 1.5 Å resolution. Human adipocyte lipid-binding protein (aP2) belongs to a family of intracellular lipid-binding proteins involved in the transport and storage of lipids. Here, the crystal structure of human aP2 with a bound palmitate is described at 1.5 Å resolution. Unlike the known crystal structure of murine aP2 in complex with palmitate, this structure shows that the fatty acid is in a folded conformation and that the loop containing Phe57 acts as a lid to regulate ligand binding by excluding solvent exposure to the central binding cavity

  12. Encapsulated phosphates reduce lipid oxidation in both ground chicken and ground beef during raw and cooked meat storage with some influence on color, pH, and cooking loss.

    Science.gov (United States)

    Kılıç, B; Simşek, A; Claus, J R; Atılgan, E

    2014-05-01

    Effects of encapsulated sodium tripolyphosphate (STP), sodium hexametaphosphate (HMP) and sodium pyrophosphate (SPP) on lipid oxidation in uncooked (0, 2, 24h) and cooked (0, 1, 7 d) ground chicken and beef during storage were determined. Ten phosphate treatments included a control (no phosphate), three unencapsulated (u) at 0.5% and three encapsulated (e) phosphates (0.5%) each at a low (e-low) and high (e-high) coating level. Two heating rates (slow, fast) were investigated. Cooking loss (CL), pH, color, orthophosphate (OP), TBARS and lipid hydroperoxides (LPO) were determined. A fast heating and uSTP resulted in lower CL (pphosphates and increased coating level reduced OP (pphosphates and the greater coating level had no effect on the pH in cooked samples. Not increased coating level but encapsulated phosphates decreased lipid oxidation in cooked samples (p<0.05). Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. 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...

  14. Lipid and protein oxidation of α-linolenic acid-enriched pork during refrigerated storage as influenced by diet supplementation with olive leaves (Olea europea L.) or α-tocopheryl acetate.

    Science.gov (United States)

    Botsoglou, Evropi; Govaris, Alexander; Ambrosiadis, Ioannis; Fletouris, Dimitrios

    2012-12-01

    The objective of this study was to evaluate the effect of diet supplementation with olive leaves or α-tocopheryl acetate on lipid and protein oxidation of raw and cooked n-3 enriched-pork during refrigerated storage. Enrichment of pork with α-linolenic acid through diet supplementation with linseed oil enhanced (p≤0.05) lipid oxidation in both raw and cooked chops but had no effect (p>0.05) on protein oxidation during refrigerated storage while decreasing (p≤0.05) the sensory attributes of cooked pork. Diet supplementation with olive leaves or α-tocopheryl acetate had no effect (p>0.05) on the fatty acid composition of pork but decreased (p≤0.05) lipid oxidation while exerting no effect (p>0.05) on protein oxidation in both raw and cooked α-linolenic acid-enriched chops stored and chilled for 9 days. Moreover, olive leaves and α-tocopheryl acetate supplemented at 10 g/kg and 200mg/kg diet, respectively, exerted (p≤0.05) a beneficial effect on the sensory attributes of cooked α-linolenic acid-enriched pork chops. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Mitochondria-associated ER membranes (MAMs) and lysosomal storage diseases.

    Science.gov (United States)

    Annunziata, Ida; Sano, Renata; d'Azzo, Alessandra

    2018-02-28

    Lysosomal storage diseases (LSDs) comprise a large group of disorders of catabolism, mostly due to deficiency of a single glycan-cleaving hydrolase. The consequent endo-lysosomal accumulation of undigested or partially digested substrates in cells of virtually all organs, including the nervous system, is diagnostic of these diseases and underlies pathogenesis. A subgroup of LSDs, the glycosphingolipidoses, are caused by deficiency of glycosidases that process/degrade sphingolipids and glycosphingolipids (GSLs). GSLs are among the lipid constituents of mammalian membranes, where they orderly distribute and, together with a plethora of membrane proteins, contribute to the formation of discrete membrane microdomains or lipid rafts. The composition of intracellular membranes enclosing organelles reflects that at the plasma membrane (PM). Organelles have the tendencies to tether to one another and to the PM at specific membrane contact sites that, owing to their lipid and protein content, resemble PM lipid rafts. The focus of this review is on the MAMs, mitochondria associated ER membranes, sites of juxtaposition between ER and mitochondria that function as biological hubs for the exchange of molecules and ions, and control the functional status of the reciprocal organelles. We will focus on the lipid components of the MAMs, and highlight how failure to digest or process the sialylated GSL, GM1 ganglioside, in lysosomes alters the lipid conformation and functional properties of the MAMs and leads to neuronal cell death and neurodegeneration.

  16. The fate of lipids during development and cold-storage of eggs in the laboratory-reared calanoid copepod, Acartia tonsa Dana, and in response to different algal diets

    DEFF Research Database (Denmark)

    Støttrup, Josianne; Bell, J.G.; Sargent, J.R.

    1999-01-01

    : the cryptophyte Rhodomonas baltica, the haptophyte Isochrysis galbana clone T- iso, the diatom Thalassiosira weissflogii and the dinoflagellate Heterocapsa triquetra. Further, the effect of cold storage of eggs on the lipid composition of the newly hatched nauplii was examined. During development, the fatty acid...... composition changes from a tendency towards high levels of long-chain polyunsaturated fatty acids in the early developmental stages towards a tendency to accumulate more saturated and monounsaturated fatty acids in the later developmental stages. However, the content and composition of polyunsaturated fatty...

  17. The Role of Autophagy in Intracellular Pathogen Nutrient Acquisition

    Directory of Open Access Journals (Sweden)

    Shaun eSteele

    2015-06-01

    Full Text Available Following entry into host cells intracellular pathogens must simultaneously evade innate host defense mechanisms and acquire energy and anabolic substrates from the nutrient-limited intracellular environment. Most of the potential intracellular nutrient sources are stored within complex macromolecules that are not immediately accessible by intracellular pathogens. To obtain nutrients for proliferation, intracellular pathogens must compete with the host cell for newly-imported simple nutrients or degrade host nutrient storage structures into their constituent components (fatty acids, carbohydrates and amino acids. It is becoming increasingly evident that intracellular pathogens have evolved a wide variety of strategies to accomplish this task. One recurrent microbial strategy is to exploit host degradative processes that break down host macromolecules into simple nutrients that the microbe can use. Herein we focus on how a subset of bacterial, viral and eukaryotic pathogens leverage the host process of autophagy to acquire nutrients that support their growth within infected cells

  18. Lipid Production from Nannochloropsis.

    Science.gov (United States)

    Ma, Xiao-Nian; Chen, Tian-Peng; Yang, Bo; Liu, Jin; Chen, Feng

    2016-03-25

    Microalgae are sunlight-driven green cell factories for the production of potential bioactive products and biofuels. Nannochloropsis represents a genus of marine microalgae with high photosynthetic efficiency and can convert carbon dioxide to storage lipids mainly in the form of triacylglycerols and to the ω-3 long-chain polyunsaturated fatty acid eicosapentaenoic acid (EPA). Recently, Nannochloropsis has received ever-increasing interests of both research and public communities. This review aims to provide an overview of biology and biotechnological potential of Nannochloropsis, with the emphasis on lipid production. The path forward for the further exploration of Nannochloropsis for lipid production with respect to both challenges and opportunities is also discussed.

  19. Following Intracellular Cholesterol Transport by Linear and Non-Linear Optical Microscopy of Intrinsically Fluorescent Sterols

    DEFF Research Database (Denmark)

    Wustner, D.

    2012-01-01

    Elucidation of intracellular cholesterol transport is important for understanding the molecular basis of several metabolic and neuronal diseases, like atheroclerosis or lysosomal storage disorders. Progress in this field depends crucially on the development of new technical approaches to follow...... the cellular movement of this essential lipid molecule. In this article, a survey of the various methods being used for analysis of sterol trafficking is given. Various classical biochemical methods are presented and their suitability for analysis of sterol trafficking is assessed. Special emphasis...... analysis like pixel-wise bleach rate fitting and multiphoton image correlation spectroscopy are introduced. Several applications of the new technology including observation of vectorial sterol trafficking in polarized human hepatoma cells for investigation of reverse cholesterol transport are presented....

  20. Liver histology of an afibrinogenemic patient with the Bbeta-L353R mutation showing no evidence of hepatic endoplasmic reticulum storage disease (ERSD); comparative study in COS-1 cells of the intracellular processing of the Bbeta-L353R fibrinogen vs. the ERSD-associated gamma-G284R mutant.

    Science.gov (United States)

    Duga, S; Braidotti, P; Asselta, R; Maggioni, M; Santagostino, E; Pellegrini, C; Coggi, G; Malcovati, M; Tenchini, M L

    2005-04-01

    Type I fibrinogen deficiencies (hypofibrinogenemia and afibrinogenemia) are rare congenital disorders characterized by low or unmeasurable plasma fibrinogen antigen levels. Their genetic bases are represented by mutations within the three fibrinogen genes. Among the 11 reported missense mutations, a few have been characterized by expression studies and found to have an impaired fibrinogen assembly and/or secretion. Histopathological analyses were previously reported in two hypofibrinogenemic cases with discernible hepatic disease, revealing that both underlying mutations (gamma-Gly284Arg and gamma-Arg375Trp) were associated with hepatic fibrinogen endoplasmic reticulum storage disease (ERSD). The objective of this study was to investigate the liver histology in an afibrinogenemic patient, homozygous for the Bbeta-Leu353Arg mutation, and to study the intracellular processing of the mutant protein. Liver histology was evaluated by light microscopy, electron microscopy and immunocytochemistry. Intracellular processing of mutant fibrinogen was analyzed by pulse-chase labeling and immunoprecipitation experiments. Messenger RNA levels were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR). The histopathological characterization of the liver showed no signs of fibrinogen accumulation, a difference from the previously reported findings in two hypofibrinogenemic kindreds with ERSD. To evaluate whether the Bbeta-Leu353Arg mutation and the ERSD-associated gamma-Gly284Arg mutation affected intracellular fibrinogen trafficking differently, both mutant proteins were expressed in COS-1 cells. Bbeta-Leu353Arg led to a more severe secretion defect, but no differences that could explain phenotype-genotype correlation were found in the intracellular processing. Endoglycosidase-H analysis demonstrated a secretion block before translocation to the Golgi medial stacks. Real-time RT-PCR studies showed normal levels of the Bbeta mRNA in the patient's liver

  1. Heart, lipids and hormones.

    Science.gov (United States)

    Wolf, Peter; Winhofer, Yvonne; Krššák, Martin; Krebs, Michael

    2017-05-01

    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. © 2017 The authors.

  2. 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.

  3. 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. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  4. Potato peel extract as a natural antioxidant in chilled storage of minced horse mackerel (Trachurus trachurus): Effect on lipid and protein oxidation

    DEFF Research Database (Denmark)

    Farvin, Sabeena; Grejsen, Helene Drejer; Jacobsen, Charlotte

    2012-01-01

    The present work was undertaken to examine the utilisation of potato peel, a waste material, as a source of natural antioxidants for retarding lipid and protein oxidation in minced mackerel. Mackerel mince with two different concentrations (2.4 or 4.8g/kg) of water or ethanol extracts of potato...... peel and a control with no added extracts were prepared. The samples were stored at 5°C for 96h and the sampling was done at time points 0, 24, 48 and 96h. The ethanol extracts, which contained high amounts of phenolic compounds, was found to be very effective in retarding lipid and protein oxidation...... as it resulted in low levels of peroxide value, volatiles, carbonyl compounds and protected against the loss of α-tocopherol and tryptophan and tyrosine residues. Water extracts was less efficient especially at higher concentrations, which might be due to lower phenolic content or due to the pro-oxidative nature...

  5. Activation of 5-[125I]iodonaphthyl-1-azide via excitation of fluorescent (N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)) lipid analogs in living cells. A potential tool for identification of compartment-specific proteins and proteins involved in intracellular transport and metabolism of lipids

    International Nuclear Information System (INIS)

    Rosenwald, A.G.; Pagano, R.E.; Raviv, Y.

    1991-01-01

    We describe a new technique for analysis of proteins located near fluorescent lipid analogs in intact living cells using the membrane-permeant, photoactivatable probe, 5-[ 125 I]iodonaphthyl-1-azide ([ 125 I]INA). [ 125 I] INA can be activated directly with UV light or indirectly through excitation of adjacent fluorophores (photosensitizers) with visible light to modify nearby proteins covalently with 125 I. In this report we demonstrate that fluorescent phospholipids and sphingolipids containing N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-6-aminocaproic acid serve as appropriate photosensitizers for [ 125 I]INA. Using Chinese hamster ovary fibroblasts, we optimized the labeling conditions with respect to lipid concentration and time of irradiation and then examined the profiles of cellular proteins that were labeled when fluorescent analogs of ceramide, sphingomyelin, and phosphatidic acid were used as photosensitizers in living cells. The use of different fluorescent lipids, which label different subcellular compartments of cells as determined by fluorescence microscopy, derivatized different sets of cellular proteins with 125 I. The labeled proteins were subsets of the total set of proteins available for derivatization as determined by direct activation of [ 125 I]INA. Most proteins labeled by this procedure were pelleted by centrifugation of cell lysates at high speed (260,000 x g), but several soluble proteins were also labeled under these conditions. The implications of using this technique for identification of compartment-specific proteins and proteins involved in lipid metabolism and transport are discussed

  6. Internalization of modified lipids by CD36 and SR-A leads to hepatic inflammation and lysosomal cholesterol storage in Kupffer cells.

    Directory of Open Access Journals (Sweden)

    Veerle Bieghs

    Full Text Available Non-alcoholic steatohepatitis (NASH is characterized by steatosis and inflammation, which can further progress into fibrosis and cirrhosis. Recently, we demonstrated that combined deletion of the two main scavenger receptors, CD36 and macrophage scavenger receptor 1 (MSR1, which are important for modified cholesterol-rich lipoprotein uptake, reduced NASH. The individual contributions of these receptors to NASH and the intracellular mechanisms by which they contribute to inflammation have not been established. We hypothesize that CD36 and MSR1 contribute independently to the onset of inflammation in NASH, by affecting intracellular cholesterol distribution inside Kupffer cells (KCs.Ldlr(-/- mice were transplanted with wild-type (Wt, Cd36(-/- or Msr1(-/- bone marrow and fed a Western diet for 3 months. Cd36(-/-- and Msr1(-/-- transplanted (tp mice showed a similar reduction in hepatic inflammation compared to Wt-tp mice. While the total amount of cholesterol inside KCs was similar in all groups, KCs of Cd36(-/-- and Msr1(-/--tp mice showed increased cytoplasmic cholesterol accumulation, while Wt-tp mice showed increased lysosomal cholesterol accumulation.CD36 and MSR1 contribute similarly and independently to the progression of inflammation in NASH. One possible explanation for the inflammatory response related to expression of these receptors could be abnormal cholesterol trafficking in KCs. These data provide a new basis for prevention and treatment of NASH.

  7. Safety and potential efficacy of gemfibrozil as a supportive treatment for children with late infantile neuronal ceroid lipofuscinosis and other lipid storage disorders.

    Science.gov (United States)

    Kim, Kyeongsoon; Kleinman, Hynda K; Lee, Hahn-Jun; Pahan, Kalipada

    2017-06-17

    Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is a group of genetically distinct lysosomal disorders that mainly affect the central nervous system, resulting in progressive motor and cognitive decline primarily in children. Multiple distinct genes involved in the metabolism of lipids have been identified to date with various mutations in this family of diseases. There is no cure for these diseases but some new therapeutic approaches have been tested that offer more hope than the standard palliative care. Many of the therapeutic advances require invasive procedures but some progress in slowing the disease has been found and more options can be expected in the future. We also review the literature on children with disease/conditions other than NCL for the non-invasive use, safety, and tolerability of a lipid-lowering drug, gemfibrozil, as a potential treatment for NCLs. Gemfibrozil has shown efficacy in an animal model of NCL known as CLN2 (late infantile classic juvenile) and has been shown to be safe for lowering lipids in children. Among the 200 non-NCL children found in the published literature who were treated with gemfibrozil for NCL-related problems, only 3 experienced adverse events, including 2 with muscle pain and 1 with localized linear IgA bullous dermatitis. We conclude that gemfibrozil is safe for long-term use in children, causes minimal adverse events, is well tolerated, and may delay the progression of NCLs. Gemfibrozil may potentially be an alternative to more invasive therapeutic approaches currently under investigation and has the potential to be used in combination with other therapeutic approaches.

  8. Reducible cationic lipids for gene transfer.

    Science.gov (United States)

    Wetzer, B; Byk, G; Frederic, M; Airiau, M; Blanche, F; Pitard, B; Scherman, D

    2001-01-01

    One of the main challenges of gene therapy remains the increase of gene delivery into eukaryotic cells. We tested whether intracellular DNA release, an essential step for gene transfer, could be facilitated by using reducible cationic DNA-delivery vectors. For this purpose, plasmid DNA was complexed with cationic lipids bearing a disulphide bond. This reduction-sensitive linker is expected to be reduced and cleaved in the reducing milieu of the cytoplasm, thus potentially improving DNA release and consequently transfection. The DNA--disulphide-lipid complexation was monitored by ethidium bromide exclusion, and the size of complexes was determined by dynamic light scattering. It was found that the reduction kinetics of disulphide groups in DNA--lipid complexes depended on the position of the disulphide linker within the lipid molecule. Furthermore, the internal structure of DNA--lipid particles was examined by small-angle X-ray scattering before and after lipid reduction. DNA release from lipid complexes was observed after the reduction of disulphide bonds of several lipids. Cell-transfection experiments suggested that complexes formed with selected reducible lipids resulted in up to 1000-fold higher reporter-gene activity, when compared with their analogues without disulphide bonds. In conclusion, reduction-sensitive groups introduced into cationic lipid backbones potentially allow enhanced DNA release from DNA--lipid complexes after intracellular reduction and represent a tool for improved vectorization. PMID:11389682

  9. Energy storage

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This chapter discusses the role that energy storage may have on the energy future of the US. The topics discussed in the chapter include historical aspects of energy storage, thermal energy storage including sensible heat storage, latent heat storage, thermochemical heat storage, and seasonal heat storage, electricity storage including batteries, pumped hydroelectric storage, compressed air energy storage, and superconducting magnetic energy storage, and production and combustion of hydrogen as an energy storage option

  10. Reprint of: Seasonal changes in the composition of storage and membrane lipids in overwintering larvae of the codling moth, Cydia pomonella.

    Science.gov (United States)

    Rozsypal, Jan; Koštál, Vladimír; Berková, Petra; Zahradníčková, Helena; Šimek, Petr

    2015-12-01

    The codling moth (Cydia pomonella) is a major insect pest of apples worldwide. It overwinters as a diapausing fifth instar larva. The overwintering is often a critical part of the insect life-cycle in temperate zone. This study brings detailed analysis of seasonal changes in lipid composition and fluidity in overwintering larvae sampled in the field. Fatty acid composition of triacylglycerol (TG) depots in the fat body and relative proportions of phospholipid (PL) molecular species in biological membranes were analyzed. In addition, temperature of melting (Tm) in TG depots was assessed by using differential scanning calorimetry and the conformational order (fluidity) of PL membranes was analyzed by measuring the anisotropy of fluorescence polarization of diphenylhexatriene probe in membrane vesicles. We observed a significant increase of relative proportion of linoleic acid (C18:2n6) at the expense of palmitic acid (C16:0) in TG depots during the larval transition to diapause accompanied with decreasing melting temperature of total lipids, which might increase the accessibility of depot fats for enzymatic breakdown during overwintering. The fluidity of membranes was maintained very high irrespective of developmental mode or seasonally changing acclimation status of larvae. The seasonal changes in PL composition were relatively small. We discuss these results in light of alternative survival strategies of codling moth larvae (supercooling vs. freezing), variability and low predictability of environmental conditions, and other cold tolerance mechanisms such as extending the supercooling capacity and massive accumulation of cryoprotective metabolites. Copyright © 2015. Published by Elsevier Ltd.

  11. A bacteriophage endolysin that eliminates intracellular streptococci.

    Science.gov (United States)

    Shen, Yang; Barros, Marilia; Vennemann, Tarek; Gallagher, D Travis; Yin, Yizhou; Linden, Sara B; Heselpoth, Ryan D; Spencer, Dennis J; Donovan, David M; Moult, John; Fischetti, Vincent A; Heinrich, Frank; Lösche, Mathias; Nelson, Daniel C

    2016-03-15

    PlyC, a bacteriophage-encoded endolysin, lyses Streptococcus pyogenes (Spy) on contact. Here, we demonstrate that PlyC is a potent agent for controlling intracellular Spy that often underlies refractory infections. We show that the PlyC holoenzyme, mediated by its PlyCB subunit, crosses epithelial cell membranes and clears intracellular Spy in a dose-dependent manner. Quantitative studies using model membranes establish that PlyCB interacts strongly with phosphatidylserine (PS), whereas its interaction with other lipids is weak, suggesting specificity for PS as its cellular receptor. Neutron reflection further substantiates that PlyC penetrates bilayers above a PS threshold concentration. Crystallography and docking studies identify key residues that mediate PlyCB-PS interactions, which are validated by site-directed mutagenesis. This is the first report that a native endolysin can traverse epithelial membranes, thus substantiating the potential of PlyC as an antimicrobial for Spy in the extracellular and intracellular milieu and as a scaffold for engineering other functionalities.

  12. Effect of storage and processing of Brazilian flaxseed on lipid and lignan contents Efeito do armazenamento e do processamento da linhaça brasileira em seus teores de lipídios e lignanas

    Directory of Open Access Journals (Sweden)

    Renée Leão Simbalista

    2012-06-01

    Full Text Available Flaxseed has been widely studied around the world; its incorporation into products habitually consumed by human populations has been stimulated due to its unique nutritional value. The objective of this study was to evaluate the chemical composition of Brazilian flaxseed, to analyze the stability of lipids present in whole flaxseed flour (WFF or partially defatted flaxseed flour (DFF stored under several temperatures, and to investigate the effect of bread making on a product containing flaxseed. Whole flaxseed flour presented (g.100 g-1 25.7 of insoluble fiber, 10.7 of soluble fiber, 38.9 of lipids, and 2.65 of lignan. Defatted flaxseed flour presented 65% less lipids, 36% more fiber and 56% more lignan than whole flaxseed flour. The fatty acid profile was maintained in the defatted flaxseed flour, and it presented a stable composition during storage under ambient temperature, refrigeration, and freezing. The fatty acid profile was similar in the bread containing defatted flaxseed flour after dough development, baking, and storage at room temperature or refrigerated. After baking, 89% of the lignan content was kept in bread. Results show that Brazilian flaxseed has an interesting chemical composition, and that defatted flaxseed, by-product of lipid extraction, presents a good stability to grind and storage under several temperatures. Thus, defatted flaxseed flour can be incorporated in bread, increasing its nutritional and functional value.A semente de linhaça vem sendo estudada por pesquisadores em todo o mundo; sua incorporação em produtos habitualmente consumidos pela população vem sendo estimulada devido a seu destacado valor nutricional. Objetivos: avaliar a composição da linhaça brasileira, analisar a estabilidade dos lipídios presentes na farinha de linhaça integral (WFF ou na farinha parcialmente desengordurada (DFF, estocadas sob diferentes temperaturas, e investigar o efeito do processamento em pão contendo linhaça. A

  13. Lipid Profile

    Science.gov (United States)

    ... Known As Coronary Risk Panel Formal Name Lipid Profile This article was last reviewed on June 29, ... phospholipid molecules. The particles measured with a lipid profile are classified by their density into high-density ...

  14. Three-dimensional label-free imaging and quantification of lipid droplets in live hepatocytes

    Science.gov (United States)

    Kim, Kyoohyun; Lee, Seoeun; Yoon, Jonghee; Heo, Jihan; Choi, Chulhee; Park, Yongkeun

    2016-11-01

    Lipid droplets (LDs) are subcellular organelles with important roles in lipid storage and metabolism and involved in various diseases including cancer, obesity, and diabetes. Conventional methods, however, have limited ability to provide quantitative information on individual LDs and have limited capability for three-dimensional (3-D) imaging of LDs in live cells especially for fast acquisition of 3-D dynamics. Here, we present an optical method based on 3-D quantitative phase imaging to measure the 3-D structural distribution and biochemical parameters (concentration and dry mass) of individual LDs in live cells without using exogenous labelling agents. The biochemical change of LDs under oleic acid treatment was quantitatively investigated, and 4-D tracking of the fast dynamics of LDs revealed the intracellular transport of LDs in live cells.

  15. Acyl-Lipid Metabolism

    Science.gov (United States)

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2013-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:23505340

  16. Microtargeting cancer metabolism: opening new therapeutic windows based on lipid metabolism

    Science.gov (United States)

    Gómez de Cedrón, Marta; Ramírez de Molina, Ana

    2016-01-01

    Metabolic reprogramming has emerged as a hallmark of cancer. MicroRNAs are noncoding RNAs that posttranscriptionally repress the expression of target mRNAs implicated in multiple physiological processes, including apoptosis, differentiation, and cancer. MicroRNAs can affect entire biological pathways, making them good candidates for therapeutic intervention compared with classical single target approaches. Moreover, microRNAs may become more relevant in the fine-tuning adaptation to stress situations, such as oncogenic events, hypoxia, nutrient deprivation, and oxidative stress. Furthermore, artificial microRNAs can be designed to modulate the expression of multiple targets of a specific pathway. In this review, we describe the metabolic reprogramming associated to cancer, with a special interest in the altered lipid metabolism. Next, we describe specific features of microRNAs that make them relevant to target cancer cell metabolism. Finally, in an attempt to open new therapeutic windows, we emphasize two exciting scenarios for microRNA-mediated intervention that need to be further explored: 1) the cooperation between FA biosynthesis (lipogenesis) and FA oxidation as complementary partners for the survival of cancer cells; and 2) the regulation of the intracellular lipid content modulating both lipid storage into lipid droplets, and lipid mobilization through lipolysis and/or lipophagy. PMID:26630911

  17. Modulation of Lipid Droplet Metabolism—A Potential Target for Therapeutic Intervention in Flaviviridae Infections

    Directory of Open Access Journals (Sweden)

    Jingshu Zhang

    2017-11-01

    Full Text Available Lipid droplets (LDs are endoplasmic reticulum (ER-related dynamic organelles that store and regulate fatty acids and neutral lipids. They play a central role in cellular energy storage, lipid metabolism and cellular homeostasis. It has become evident that viruses have co-evolved in order to exploit host lipid metabolic pathways. This is especially characteristic of the Flaviviridae family, including hepatitis C virus (HCV and several flaviviruses. Devoid of an appropriate lipid biosynthetic machinery of their own, these single-strand positive-sense RNA viruses can induce dramatic changes in host metabolic pathways to establish a favorable environment for viral multiplication and acquire essential components to facilitate their assembly and traffic. Here we have reviewed the current knowledge on the intracellular life cycle of those from the Flaviviridae family, with particular emphasis on HCV and dengue virus (DENV, and their association with the biosynthesis and metabolism of LDs, with the aim to identify potential antiviral targets for development of novel therapeutic interventions.

  18. The SwissLipids knowledgebase for lipid biology.

    OpenAIRE

    Aimo, L.; Liechti, R.; Hyka-Nouspikel, N.; Niknejad, A.; Gleizes, A.; Götz, L.; Kuznetsov, D.; David, F.P.; van der Goot, F.G.; Riezman, H.; Bougueleret, L.; Xenarios, I.; Bridge, A.

    2015-01-01

    Motivation: Lipids are a large and diverse group of biological molecules with roles in membrane formation, energy storage and signaling. Cellular lipidomes may contain tens of thousands of structures, a staggering degree of complexity whose significance is not yet fully understood. High-throughput mass spectrometry-based platforms provide a means to study this complexity, but the interpretation of lipidomic data and its integration with prior knowledge of lipid biology suffers from a lack of ...

  19. Biochemical Storage Lesions Occurring in Nonirradiated and Irradiated Red Blood Cells: A Brief Review

    Directory of Open Access Journals (Sweden)

    F. Adams

    2015-01-01

    Full Text Available Red blood cells undergo a series of biochemical fluctuations during 35–42-day storage period at 1°C to 6°C. The sodium/potassium pump is immobilised causing a decrease in intracellular potassium with an increase in cytoplasmic sodium levels, glucose levels decline, and acidosis occurs as a result of low pH levels. The frailty of stored erythrocytes triggers the formation of haemoglobin-containing microparticles and the release of cell-free haemoglobin which may add to transfusion difficulties. Lipid peroxidation, oxidative stress to band 3 structures, and other morphological and structural molecular changes also occur leading to spheroechinocytes and osmotic fragility. These changes that transpire in the red cells during the storage period are referred to as “storage lesions.” It is well documented that gamma irradiation exacerbates storage lesions and the reports of increased potassium levels leading to adverse reactions observed in neonates and infants have been of particular concern. There are, however, remarkably few systematic studies comparing the in vitro storage lesions of irradiated and nonirradiated red cell concentrates and it has been suggested that the impact of storage lesions on leucocyte reduced red blood cell concentrate (RBCC is incomplete. The review examines storage lesions in red blood cells and their adverse effects in reference to blood transfusion.

  20. 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...

  1. Energy Storage.

    Science.gov (United States)

    Eaton, William W.

    Described are technological considerations affecting storage of energy, particularly electrical energy. The background and present status of energy storage by batteries, water storage, compressed air storage, flywheels, magnetic storage, hydrogen storage, and thermal storage are discussed followed by a review of development trends. Included are…

  2. 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 diverse...... aspects of cellular life. Here we discuss the mechanisms by which rapid flip-flop occurs, and what role lipid flipping plays in membrane homeostasis and cell growth. We focus on conceptual aspects, highlighting mechanistic insights from biochemical and in silico experiments, and the recent, ground......-breaking identification of a number of lipid scramblases....

  3. 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

    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......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...... 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...

  4. Liposome-based Formulation for Intracellular Delivery of Functional Proteins

    Directory of Open Access Journals (Sweden)

    Benoît Chatin

    2015-01-01

    Full Text Available The intracellular delivery of biologically active protein represents an important emerging strategy for both fundamental and therapeutic applications. Here, we optimized in vitro delivery of two functional proteins, the β-galactosidase (β-gal enzyme and the anti-cytokeratin8 (K8 antibody, using liposome-based formulation. The guanidinium-cholesterol cationic lipid bis (guanidinium-tren-cholesterol (BGTC (bis (guanidinium-tren-cholesterol combined to the colipid dioleoyl phosphatidylethanolamine (DOPE (dioleoyl phosphatidylethanolamine was shown to efficiently deliver the β-gal intracellularly without compromising its activity. The lipid/protein molar ratio, protein amount, and culture medium were demonstrated to be key parameters affecting delivery efficiency. The protein itself is an essential factor requiring selection of the appropriate cationic lipid as illustrated by low K8 binding activity of the anti-K8 antibody using guanidinium-based liposome. Optimization of various lipids led to the identification of the aminoglycoside lipid dioleyl succinyl paromomycin (DOSP associated with the imidazole-based helper lipid MM27 as a potent delivery system for K8 antibody, achieving delivery in 67% of HeLa cells. Cryo-transmission electron microscopy showed that the structure of supramolecular assemblies BGTC:DOPE/β-gal and DOSP:MM27/K8 were different depending on liposome types and lipid/protein molar ratio. Finally, we observed that K8 treatment with DOSP:MM27/K8 rescues the cyclic adenosine monophosphate (cAMP-dependent chloride efflux in F508del-CFTR expressing cells, providing a new tool for the study of channelopathies.

  5. 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...

  6. Blood lipid metabolites and meat lipid peroxidation responses of ...

    African Journals Online (AJOL)

    Blood samples were collected from broilers to evaluate serum biochemical metabolites on day 41. Thigh meat samples were provided and analysed after 1, 5 and 10 days' storage to evaluate lipid peroxidation at the end of the experiment. Fat and protein contents of thigh muscle and abdominal fat weight were measured ...

  7. Microorganism lipid droplets and biofuel development

    OpenAIRE

    Liu, Yingmei; Zhang, Congyan; Shen, Xipeng; Zhang, Xuelin; Cichello, Simon; Guan, Hongbin; Liu, Pingsheng

    2013-01-01

    Lipid droplet (LD) is a cellular organelle that stores neutral lipids as a source of energy and carbon. However, recent research has emerged that the organelle is involved in lipid synthesis, transportation, and metabolism, as well as mediating cellular protein storage and degradation. With the exception of multi-cellular organisms, some unicellular microorganisms have been observed to contain LDs. The organelle has been isolated and characterized from numerous organisms. Triacylglycerol (TAG...

  8. INTRACELLULAR Ca2+ HOMEOSTASIS

    Directory of Open Access Journals (Sweden)

    Shahdevi Nandar Kurniawan

    2015-01-01

    Full Text Available Ca2+ signaling functions to regulate many cellular processes. Dynamics of Ca2+ signaling or homeostasis is regulated by the interaction between ON and OFF reactions that control Ca2+ flux in both the plasma membrane and internal organelles such as the endoplasmic reticulum (ER and mitochondria. External stimuli activate the ON reactions, which include Ca2+ into the cytoplasm either through channels in the plasma membrane or from internal storage like in ER. Most of the cells utilize both channels/sources, butthere area few cells using an external or internal source to control certain processes. Most of the Ca2+ entering the cytoplasm adsorbed to the buffer, while a smaller part activate effect or to stimulate cellular processes. Reaction OFF is pumping of cytoplasmic Ca2+ using a combination mechanism of mitochondrial and others. Changes in Ca2+ signal has been detected in various tissues isolated from animals induced into diabetes as well as patients with diabetes. Ca2+ signal interference is also found in sensory neurons of experimental animals with diabetes. Ca2+ signaling is one of the main signaling systems in the cell.

  9. The Role of Lipid Metabolism in T Lymphocyte Differentiation and Survival

    Directory of Open Access Journals (Sweden)

    Duncan Howie

    2018-01-01

    Full Text Available The differentiation and effector functions of both the innate and adaptive immune system are inextricably linked to cellular metabolism. The features of metabolism which affect both arms of the immune system include metabolic substrate availability, expression of enzymes, transport proteins, and transcription factors which control catabolism of these substrates, and the ability to perform anabolic metabolism. The control of lipid metabolism is central to the appropriate differentiation and functions of T lymphocytes, and ultimately to the maintenance of immune tolerance. This review will focus on the role of fatty acid (FA metabolism in T cell differentiation, effector function, and survival. FAs are important sources of cellular energy, stored as triglycerides. They are also used as precursors to produce complex lipids such as cholesterol and membrane phospholipids. FA residues also become incorporated into hormones and signaling moieties. FAs signal via nuclear receptors and their channeling, between storage as triacyl glycerides or oxidation as fuel, may play a role in survival or death of the cell. In recent years, progress in the field of immunometabolism has highlighted diverse roles for FA metabolism in CD4 and CD8 T cell differentiation and function. This review will firstly describe the sensing and modulation of the environmental FAs and lipid intracellular signaling and will then explore the key role of lipid metabolism in regulating the balance between potentially damaging pro-inflammatory and anti-inflammatory regulatory responses. Finally the complex role of extracellular FAs in determining cell survival will be discussed.

  10. The intracellular pharmacokinetics of terminally capped peptides.

    NARCIS (Netherlands)

    Ruttekolk, I.R.R.; Witsenburg, J.J.; Glauner, H.B.; Bovee-Geurts, P.H.M.; Ferro, E.S.; Verdurmen, W.P.R.; Brock, R.E.

    2012-01-01

    With significant progress in delivery technologies, peptides and peptidomimetics are receiving increasing attention as potential therapeutics also for intracellular applications. However, analyses of the intracellular behavior of peptides are a challenge; therefore, knowledge on the intracellular

  11. Functional genomics of intracellular bacteria.

    Science.gov (United States)

    de Barsy, Marie; Greub, Gilbert

    2013-07-01

    During the genomic era, a large amount of whole-genome sequences accumulated, which identified many hypothetical proteins of unknown function. Rapidly, functional genomics, which is the research domain that assign a function to a given gene product, has thus been developed. Functional genomics of intracellular pathogenic bacteria exhibit specific peculiarities due to the fastidious growth of most of these intracellular micro-organisms, due to the close interaction with the host cell, due to the risk of contamination of experiments with host cell proteins and, for some strict intracellular bacteria such as Chlamydia, due to the absence of simple genetic system to manipulate the bacterial genome. To identify virulence factors of intracellular pathogenic bacteria, functional genomics often rely on bioinformatic analyses compared with model organisms such as Escherichia coli and Bacillus subtilis. The use of heterologous expression is another common approach. Given the intracellular lifestyle and the many effectors that are used by the intracellular bacteria to corrupt host cell functions, functional genomics is also often targeting the identification of new effectors such as those of the T4SS of Brucella and Legionella.

  12. Salt modulates the stability and lipid binding affinity of the adipocyte lipid-binding proteins

    Science.gov (United States)

    Schoeffler, Allyn J.; Ruiz, Carmen R.; Joubert, Allison M.; Yang, Xuemei; LiCata, Vince J.

    2003-01-01

    Adipocyte lipid-binding protein (ALBP or aP2) is an intracellular fatty acid-binding protein that is found in adipocytes and macrophages and binds a large variety of intracellular lipids with high affinity. Although intracellular lipids are frequently charged, biochemical studies of lipid-binding proteins and their interactions often focus most heavily on the hydrophobic aspects of these proteins and their interactions. In this study, we have characterized the effects of KCl on the stability and lipid binding properties of ALBP. We find that added salt dramatically stabilizes ALBP, increasing its Delta G of unfolding by 3-5 kcal/mol. At 37 degrees C salt can more than double the stability of the protein. At the same time, salt inhibits the binding of the fluorescent lipid 1-anilinonaphthalene-8-sulfonate (ANS) to the protein and induces direct displacement of the lipid from the protein. Thermodynamic linkage analysis of the salt inhibition of ANS binding shows a nearly 1:1 reciprocal linkage: i.e. one ion is released from ALBP when ANS binds, and vice versa. Kinetic experiments show that salt reduces the rate of association between ANS and ALBP while simultaneously increasing the dissociation rate of ANS from the protein. We depict and discuss the thermodynamic linkages among stability, lipid binding, and salt effects for ALBP, including the use of these linkages to calculate the affinity of ANS for the denatured state of ALBP and its dependence on salt concentration. We also discuss the potential molecular origins and potential intracellular consequences of the demonstrated salt linkages to stability and lipid binding in ALBP.

  13. Control of intracellular heme levels: Heme transporters and heme oxygenases

    OpenAIRE

    Khan, Anwar A.; Quigley, John G.

    2011-01-01

    Heme serves as a co-factor in proteins involved in fundamental biological processes including oxidative metabolism, oxygen storage and transport, signal transduction and drug metabolism. In addition, heme is important for systemic iron homeostasis in mammals. Heme has important regulatory roles in cell biology, yet excessive levels of intracellular heme are toxic; thus, mechanisms have evolved to control the acquisition, synthesis, catabolism and expulsion of cellular heme. Recently, a number...

  14. Cytoplasmic lipid bodies of human neutrophilic leukocytes

    International Nuclear Information System (INIS)

    Weller, P.F.; Ackerman, S.J.; Nicholson-Weller, A.; Dvorak, A.M.

    1989-01-01

    The morphology and function of cytoplasmic lipid bodies in human neutrophils were evaluated. By transmission electron microscopy, neutrophil lipid bodies were cytoplasmic inclusions, usually several microns in diameter, that occasionally coalesced to attain a diameter up to 7 microM. Neutrophil lipid bodies were not enveloped by membrane but were often surrounded by a more electron-dense shell at their periphery. Normal peripheral blood neutrophils contained an average of approximately one lipid body per cell. Lipid bodies appeared in greater numbers in neutrophils from inflammatory lesions. Perturbation of neutrophils during conventional methods of cell isolation and purification modestly increased lipid body numbers in neutrophils, whereas incubation of neutrophils with 1 microM oleic acid rapidly induced lipid body formation over 30 to 60 minutes. After granulocytes were incubated for 2 hours with 3H-fatty acids, including arachidonic, oleic, and palmitic acids, electron microscopic autoradiography demonstrated that lipid bodies represented the predominant intracellular sites of localization of each of the three 3H-fatty acids. There was lesser labeling noted in the perinuclear cisterna, but not in cell membranes. Virtually all of each of the three 3H-fatty acids incorporated by the neutrophils were esterified into chromatographically resolved classes of neutral lipids or phospholipids. These findings indicate that cytoplasmic lipid bodies are more prominent in neutrophils in vivo engaged in inflammatory responses and that these organelles in human neutrophils function as sites of deposition of esterified, incorporated fatty acids

  15. Oxidative deterioration of pork during superchilling storage

    DEFF Research Database (Denmark)

    Pomponio, Luigi; Ruiz Carrascal, Jorge

    2017-01-01

    BACKGROUND: In superchilling (SC), meat is kept at temperatures around 1 °C below its initial freezing point, leading to a significant increase in shelf life. This study aimed to address the oxidative changes taking place in pork loins during prolonged storage at SC temperature. Loins were stored...... after 12 weeks of SC storage were similar to those after 4 weeks at CH conditions. However, hexanal content peaked by the end of SC storage, pointing to a potential accumulation of compounds from lipid oxidation during SC storage. CONCLUSION: SC storage of pork slows down the rate of lipid and protein...... either at chilling (CH) conditions (2-4 °C) for 4 weeks or at SC temperature (around -1 °C) for 12 weeks. RESULTS: Storage at SC temperature diminished the rate of lipid and protein oxidation and discoloration in pork loins, so that final levels of most oxidation products and instrumental color values...

  16. A Comparison of Cholesterol Uptake and Storage in Inflammatory and Noninflammatory Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Breonna J. Martin

    2012-01-01

    Full Text Available Although there are many subtypes of breast cancer, inflammatory breast cancer (IBC is arguably the deadliest. Research over the past decade has demonstrated that IBC is a distinct entity from other forms of breast cancer. Important risk factors that have been associated with the development of aggressive breast cancers, such as IBC, include obesity and diet, which are evident in the United States, where the overconsumption of high-fat foods continues to contribute to obesity in the nation. Here we investigate differences in cholesterol uptake and storage between IBC, non-IBC, and mammary epithelial cell lines. Our results demonstrate that compared with human mammary epithelial cells (HMECs, both IBC and non-IBC cells have increased cholesterol content. IBC cells retain intracellular cholesterol esters, free cholesterol, and triglycerides in lipid-deficient environments. In contrast, we observe in cell-type-of-origin-matched non-IBC a significant decrease in lipid content under the same lipid-deficient conditions. These data suggest that cholesterol storage may be affected by the cholesterol content of the environment where the tumor cell was isolated. Here, we suggest that breast cancer cells may migrate when they are unable to obtain cholesterol from their extracellular environments.

  17. Genomic Foundation of Starch-to-Lipid Switch in Oleaginous Chlorella spp.1

    Science.gov (United States)

    Fan, Jianhua; Ning, Kang; Zeng, Xiaowei; Luo, Yuanchan; Wang, Dongmei; Hu, Jianqiang; Li, Jing; Xu, Hui; Huang, Jianke; Wan, Minxi; Wang, Weiliang; Zhang, Daojing; Shen, Guomin; Run, Conglin; Liao, Junjie; Fang, Lei; Huang, Shi; Jing, Xiaoyan; Su, Xiaoquan; Wang, Anhui; Bai, Lili; Hu, Zanmin; Xu, Jian; Li, Yuanguang

    2015-01-01

    The ability to rapidly switch the intracellular energy storage form from starch to lipids is an advantageous trait for microalgae feedstock. To probe this mechanism, we sequenced the 56.8-Mbp genome of Chlorella pyrenoidosa FACHB-9, an industrial production strain for protein, starch, and lipids. The genome exhibits positive selection and gene family expansion in lipid and carbohydrate metabolism and genes related to cell cycle and stress response. Moreover, 10 lipid metabolism genes might be originated from bacteria via horizontal gene transfer. Transcriptomic dynamics tracked via messenger RNA sequencing over six time points during metabolic switch from starch-rich heterotrophy to lipid-rich photoautotrophy revealed that under heterotrophy, genes most strongly expressed were from the tricarboxylic acid cycle, respiratory chain, oxidative phosphorylation, gluconeogenesis, glyoxylate cycle, and amino acid metabolisms, whereas those most down-regulated were from fatty acid and oxidative pentose phosphate metabolism. The shift from heterotrophy into photoautotrophy highlights up-regulation of genes from carbon fixation, photosynthesis, fatty acid biosynthesis, the oxidative pentose phosphate pathway, and starch catabolism, which resulted in a marked redirection of metabolism, where the primary carbon source of glycine is no longer supplied to cell building blocks by the tricarboxylic acid cycle and gluconeogenesis, whereas carbon skeletons from photosynthesis and starch degradation may be directly channeled into fatty acid and protein biosynthesis. By establishing the first genetic transformation in industrial oleaginous C. pyrenoidosa, we further showed that overexpression of an NAD(H) kinase from Arabidopsis (Arabidopsis thaliana) increased cellular lipid content by 110.4%, yet without reducing growth rate. These findings provide a foundation for exploiting the metabolic switch in microalgae for improved photosynthetic production of food and fuels. PMID:26486592

  18. Intracellular trafficking mechanism of cationic phospholipids including cationic liposomes in HeLa cells.

    Science.gov (United States)

    Un, K; Sakai-Kato, K; Goda, Y

    2014-07-01

    The development of gene delivery methods is essential for the achievement of effective gene therapy. Elucidation of the intracellular transfer mechanism for cationic carriers is in progress, but there are few reports regarding the intracellular trafficking processes of the cationic phospholipids taken up into cells. In the present work, the trafficking processes of a cationic phospholipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) were investigated from intracellular uptake to extracellular efflux using cationic liposomes in vitro. Following intracellular transport of liposomes via endocytosis, DOTAP was localized in the endoplasmic reticulum, Golgi apparatus, and mitochondria. Moreover, the proteins involved in DOTAP intracellular trafficking and extracellular efflux were identified. In addition, helper lipids of cationic liposomes were found to partially affect this intracellulartrafficking. These findings might provide valuable information for designing cationic carriers and avoiding unexpected toxic side effects derived from cationic liposomal components.

  19. A novel transgenic mouse model of lysosomal storage disorder.

    Science.gov (United States)

    Ortiz-Miranda, Sonia; Ji, Rui; Jurczyk, Agata; Aryee, Ken-Edwin; Mo, Shunyan; Fletcher, Terry; Shaffer, Scott A; Greiner, Dale L; Bortell, Rita; Gregg, Ronald G; Cheng, Alan; Hennings, Leah J; Rittenhouse, Ann R

    2016-11-01

    Knockout technology has proven useful for delineating functional roles of specific genes. Here we describe and provide an explanation for striking pathology that occurs in a subset of genetically engineered mice expressing a rat Ca V β2a transgene under control of the cardiac α-myosin heavy chain promoter. Lesions were limited to mice homozygous for transgene and independent of native Cacnb2 genomic copy number. Gross findings included an atrophied pancreas; decreased adipose tissue; thickened, orange intestines; and enlarged liver, spleen, and abdominal lymph nodes. Immune cell infiltration and cell engulfment by macrophages were associated with loss of pancreatic acinar cells. Foamy macrophages diffusely infiltrated the small intestine's lamina propria, while similar macrophage aggregates packed liver and splenic red pulp sinusoids. Periodic acid-Schiff-positive, diastase-resistant, iron-negative, Oil Red O-positive, and autofluorescent cytoplasm was indicative of a lipid storage disorder. Electron microscopic analysis revealed liver sinusoids distended by clusters of macrophages containing intracellular myelin "swirls" and hepatocytes with enlarged lysosomes. Additionally, build up of cholesterol, cholesterol esters, and triglycerides, along with changes in liver metabolic enzyme levels, were consistent with a lipid processing defect. Because of this complex pathology, we examined the transgene insertion site. Multiple transgene copies inserted into chromosome 19; at this same site, an approximate 180,000 base pair deletion occurred, ablating cholesterol 25-hydroxylase and partially deleting lysosomal acid lipase and CD95 Loss of gene function can account for the altered lipid processing, along with hypertrophy of the immune system, which define this phenotype, and serendipitously provides a novel mouse model of lysosomal storage disorder. Copyright © 2016 the American Physiological Society.

  20. Changes of lipids in irradiated chickens. Veraenderung der Lipide von strahlenbehandelten Broilern

    Energy Technology Data Exchange (ETDEWEB)

    Moersel, J.T.; Wende, I.; Schwarz, K. (Humboldt-Universitaet, Berlin (Germany, F.R.). Inst. fuer Lebensmittelchemie)

    1991-01-01

    Chickens were irradiated in a {sup 6}deg Co gamma irradiation source. The irradiation has been done to reduce or eliminate Salmonella. The experiments were done to test this decontamination method of chickens if changes of lipids take place. It was to be seen, that peroxidation of lipids was more rapidly as in control. The time of storage of irradiated chickens has to be shorter because of changes in lipids. After irradiation the chickens had trade quality. (orig.).

  1. Analysis of intracellular expressed proteins of Mycobacterium tuberculosis clinical isolates

    Directory of Open Access Journals (Sweden)

    Singhal Neelja

    2012-03-01

    Full Text Available Abstract Background Tuberculosis (TB is the most threatening infectious disease globally. Although progress has been made to reduce global incidence of TB, emergence of multidrug resistant (MDR TB threatens to undermine these advances. To combat the disease, novel intervention strategies effective against drug resistant and sensitive subpopulations of M. tuberculosis are urgently required as adducts in the present treatment regimen. Using THP-1 cells we have analyzed and compared the global protein expression profile of broth-cultured and intraphagosomally grown drug resistant and sensitive M.tuberculosis clinical isolates. Results On comparing the two dimensional (2-DE gels, many proteins were found to be upregulated/expressed during intracellular state which were identified by matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS. Four proteins (adenosylhomocysteinase, aspartate carbomyltransferase, putatitive thiosulfate sulfurtransferase and universal stress protein were present in both intracellular MDR and sensitive isolates and three of these belonged to intermediary metabolism and respiration category. Two proteins (alanine dehydrogenase and adenosine kinase of intracellular MDR isolate and two (glucose-6-phosphate isomerase and ATP synthase epsilon chain of intracellular sensitive isolate belonged to intermediary metabolism and respiration category. One protein (Peroxidase/Catalase of intracellular MDR and three (HSPX, 14 kDa antigen and 10 kDa chaperonin of sensitive isolate belonged to virulence, detoxification and adaptation category. ESAT-6 of intracellular MDR belonged to cell wall and cell processes category. Two proteins (Antigen 85-C and Antigen 85-A of intracellular sensitive isolate were involved in lipid metabolism while probable peptidyl-prolyl cis-trans isomerase A was involved in information pathways. Four (Rv0635, Rv1827, Rv0036c and Rv2032 of intracellular MDR and two proteins (Rv2896c and Rv2558c of

  2. Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Acar, Handan [Institute; Department; Samaeekia, Ravand [Institute; Department; Schnorenberg, Mathew R. [Institute; Department; Medical; Sasmal, Dibyendu K. [Institute; Huang, Jun [Institute; Tirrell, Matthew V. [Institute; Institute; LaBelle, James L. [Department

    2017-08-24

    Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation, and PA monomers are internalized via endocytosis. However, endocytotic sequestration and steric hindrance from the lipid tail are two major mechanisms that limit PA efficacy to target intracellular PPIs. To address these problems, we have constructed a PA platform consisting of cathepsin-B cleavable PAs in which a selective p53-based inhibitory peptide is cleaved from its lipid tail within endosomes, allowing for intracellular peptide accumulation and extracellular recycling of the lipid moiety. We monitor for cleavage and follow individual PA components in real time using a resonance energy transfer (FRET)-based tracking system. Using this platform, components in real time using a Forster we provide a better understanding and quantification of cellular internalization, trafficking, and endosomal cleavage of PAs and of the ultimate fates of each component.

  3. Design of a nanostructured lipid carrier intended to improve the treatment of tuberculosis

    Directory of Open Access Journals (Sweden)

    Pinheiro M

    2016-08-01

    Full Text Available Marina Pinheiro,1,* Ricardo Ribeiro,1,* Alexandre Vieira,1,* Fernanda Andrade,2 Salette Reis1 1IUCIBIO, REQUIMTE, Chemistry Department, Faculty of Pharmacy, 2Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal *These authors contributed equally to this work Abstract: This work aimed to design, develop, and characterize a lipid nanocarrier system for the selective delivery of rifabutin (RFB to alveolar macrophages. Lipid nanoparticles, specifically nanostructured lipid carriers (NLC, were synthetized by the high-shear homogenization and ultrasonication techniques. These nanoparticles were designed to exhibit both passive and active targeting strategies to be efficiently internalized by the alveolar macrophages, traffic to the acidified phagosomes and phagolysosomes, and release bactericidal concentrations of the antituberculosis drug intracellularly. NLC that could entrap RFB were prepared, characterized, and further functionalized with mannose. Particles’ diameter, zeta potential, morphology, drug% entrapping efficiency, and drug release kinetics were evaluated. The mannose coating process was confirmed by Fourier transform infrared. Further, the cytotoxicity of the formulations was evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5 diphenyltetrazolium bromide (MTT assay in A549, Calu-3, and Raw 264.7 cells. The diameter of NLC formulations was found to be in the range of 175–213 nm, and drug entrapping efficiency was found to be above 80%. In addition, high storage stability for the formulations was expected since they maintained the initial characteristics for 6 months. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. These results pose a strong argument that the developed nanocarrier can be explored as a promising carrier for safer and more efficient management of tuberculosis by exploiting the pulmonary route of

  4. Involvement of intracellular cAMP in epirubicin-induced vascular endothelial cell injury

    Directory of Open Access Journals (Sweden)

    Takaaki Yamada

    2016-01-01

    Full Text Available We investigated the involvement of intracellular cAMP in endothelial cell injury induced by epirubicin. Epirubicin-induced decrease in cell viability and increase in caspase-3/7 activity were reversed by a cAMP analog dibutyryl cAMP (DBcAMP or an activator of adenylate cyclase forskolin concomitant with a phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Moreover, epirubicin-induced elevation of lipid peroxide levels was attenuated by DBcAMP. Interestingly, the exposure of epirubicin decreased intracellular cAMP levels before the onset of epirubicin-induced production of lipid peroxidation. These results suggest that intracellular cAMP plays an important role in epirubicin-induced endothelial cell injury.

  5. Stochastic models of intracellular transport

    KAUST Repository

    Bressloff, Paul C.

    2013-01-09

    The interior of a living cell is a crowded, heterogenuous, fluctuating environment. Hence, a major challenge in modeling intracellular transport is to analyze stochastic processes within complex environments. Broadly speaking, there are two basic mechanisms for intracellular transport: passive diffusion and motor-driven active transport. Diffusive transport can be formulated in terms of the motion of an overdamped Brownian particle. On the other hand, active transport requires chemical energy, usually in the form of adenosine triphosphate hydrolysis, and can be direction specific, allowing biomolecules to be transported long distances; this is particularly important in neurons due to their complex geometry. In this review a wide range of analytical methods and models of intracellular transport is presented. In the case of diffusive transport, narrow escape problems, diffusion to a small target, confined and single-file diffusion, homogenization theory, and fractional diffusion are considered. In the case of active transport, Brownian ratchets, random walk models, exclusion processes, random intermittent search processes, quasi-steady-state reduction methods, and mean-field approximations are considered. Applications include receptor trafficking, axonal transport, membrane diffusion, nuclear transport, protein-DNA interactions, virus trafficking, and the self-organization of subcellular structures. © 2013 American Physical Society.

  6. 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.

  7. Lipophagy: Connecting Autophagy and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Rajat Singh

    2012-01-01

    Full Text Available Lipid droplets (LDs, initially considered “inert” lipid deposits, have gained during the last decade the classification of cytosolic organelles due to their defined composition and the multiplicity of specific cellular functions in which they are involved. The classification of LD as organelles brings along the need for their regulated turnover and recent findings support the direct contribution of autophagy to this turnover through a process now described as lipophagy. This paper focuses on the characteristics of this new type of selective autophagy and the cellular consequences of the mobilization of intracellular lipids through this process. Lipophagy impacts the cellular energetic balance directly, through lipid breakdown and, indirectly, by regulating food intake. Defective lipophagy has been already linked to important metabolic disorders such as fatty liver, obesity and atherosclerosis, and the age-dependent decrease in autophagy could underline the basis for the metabolic syndrome of aging.

  8. Seed lipids.

    Science.gov (United States)

    Wolff, I A

    1966-12-02

    Many of the newly discovered seedoil acids have reactive or unusual functional groups or other facets of molecular structure that permit their ready differentiation from oleic, linoleic, linolenic, and the other most prevalent saturated and unsaturated long-chain fatty acids. The recognition and availability of the new acids, coupled with methods that make detection and determination easy, will help studies of lipid biosynthesis in the plant and of lipid metabolism and utilization in animals, and will stimulate more studies in depth on the fine points of seedlipid structure. Correlations of structural patterns in seed lipids of particular groups of plants with classical taxonomic categories will permit clarifications, raise needed questions concerning classifications, and accelerate research in chemotaxonomy and phylogenetics. Seed lipids are particularly well suited for establishing relationships among plants because of their great variety in structure compared to the more limited structural types of amino acids, sugars, purines, and many other plant substances. The newly characterized seed oils are potentially important industrial raw materials whenever they come from agronomically promising plant species. The molecular structures of seed triglycerides have major influence on their physical properties and therefore advances in knowledge in that sphere have practical implications. For example, the unusual characteristics of cocoa butter that make it so valuable for food and confectionery use are attributed to the specific arrangement of fatty acids it its triglycerides. The glycerides are almost all 2-oleic-1,3-disaturated acid triglycerides. The physical characteristics of lard are advantageously changed by catalytically rearranging fatty acyl groups among the glycerides initially in the fat to achieve a more nearly random distribution, followed sometimes by further fractionation to remove more saturated glycerides. Through this change of glyceride structures a

  9. A Comparative Study on the Alterations of Endocytic Pathways in Multiple Lysosomal Storage Disorders.

    Science.gov (United States)

    Rappaport, Jeff; Manthe, Rachel L; Solomon, Melani; Garnacho, Carmen; Muro, Silvia

    2016-02-01

    Many cellular activities and pharmaceutical interventions involve endocytosis and delivery to lysosomes for processing. Hence, lysosomal processing defects can cause cell and tissue damage, as in lysosomal storage diseases (LSDs) characterized by lysosomal accumulation of undegraded materials. This storage causes endocytic and trafficking alterations, which exacerbate disease and hinder treatment. However, there have been no systematic studies comparing different endocytic routes in LSDs. Here, we used genetic and pharmacological models of four LSDs (type A Niemann-Pick, type C Niemann-Pick, Fabry, and Gaucher diseases) and evaluated the pinocytic and receptor-mediated activity of the clathrin-, caveolae-, and macropinocytic routes. Bulk pinocytosis was diminished in all diseases, suggesting a generic endocytic alteration linked to lysosomal storage. Fluid-phase (dextran) and ligand (transferrin) uptake via the clathrin route were lower for all LSDs. Fluid-phase and ligand (cholera toxin B) uptake via the caveolar route were both affected but less acutely in Fabry or Gaucher diseases. Epidermal growth factor-induced macropinocytosis was altered in Niemann-Pick cells but not other LSDs. Intracellular trafficking of ligands was also distorted in LSD versus wild-type cells. The extent of these endocytic alterations paralleled the level of cholesterol storage in disease cell lines. Confirming this, pharmacological induction of cholesterol storage in wild-type cells disrupted endocytosis, and model therapeutics restored uptake in proportion to their efficacy in attenuating storage. This suggests a proportional and reversible relationship between endocytosis and lipid (cholesterol) storage. By analogy, the accumulation of biological material in other diseases, or foreign material from drugs or their carriers, may cause similar deficits, warranting further investigation.

  10. Mycobacterium marinum Degrades Both Triacylglycerols and Phospholipids from Its Dictyostelium Host to Synthesise Its Own Triacylglycerols and Generate Lipid Inclusions

    Science.gov (United States)

    2017-01-01

    During a tuberculosis infection and inside lipid-laden foamy macrophages, fatty acids (FAs) and sterols are the major energy and carbon source for Mycobacterium tuberculosis. Mycobacteria can be found both inside a vacuole and the cytosol, but how this impacts their access to lipids is not well appreciated. Lipid droplets (LDs) store FAs in form of triacylglycerols (TAGs) and are energy reservoirs of prokaryotes and eukaryotes. Using the Dictyostelium discoideum/Mycobacterium marinum infection model we showed that M. marinum accesses host LDs to build up its own intracytosolic lipid inclusions (ILIs). Here, we show that host LDs aggregate at regions of the bacteria that become exposed to the cytosol, and appear to coalesce on their hydrophobic surface leading to a transfer of diacylglycerol O-acyltransferase 2 (Dgat2)-GFP onto the bacteria. Dictyostelium knockout mutants for both Dgat enzymes are unable to generate LDs. Instead, the excess of exogenous FAs is esterified predominantly into phospholipids, inducing uncontrolled proliferation of the endoplasmic reticulum (ER). Strikingly, in absence of host LDs, M. marinum alternatively exploits these phospholipids, resulting in rapid reversal of ER-proliferation. In addition, the bacteria are unable to restrict their acquisition of lipids from the dgat1&2 double knockout leading to vast accumulation of ILIs. Recent data indicate that the presence of ILIs is one of the characteristics of dormant mycobacteria. During Dictyostelium infection, ILI formation in M. marinum is not accompanied by a significant change in intracellular growth and a reduction in metabolic activity, thus providing evidence that storage of neutral lipids does not necessarily induce dormancy. PMID:28103313

  11. Mycobacterium marinum Degrades Both Triacylglycerols and Phospholipids from Its Dictyostelium Host to Synthesise Its Own Triacylglycerols and Generate Lipid Inclusions.

    Science.gov (United States)

    Barisch, Caroline; Soldati, Thierry

    2017-01-01

    During a tuberculosis infection and inside lipid-laden foamy macrophages, fatty acids (FAs) and sterols are the major energy and carbon source for Mycobacterium tuberculosis. Mycobacteria can be found both inside a vacuole and the cytosol, but how this impacts their access to lipids is not well appreciated. Lipid droplets (LDs) store FAs in form of triacylglycerols (TAGs) and are energy reservoirs of prokaryotes and eukaryotes. Using the Dictyostelium discoideum/Mycobacterium marinum infection model we showed that M. marinum accesses host LDs to build up its own intracytosolic lipid inclusions (ILIs). Here, we show that host LDs aggregate at regions of the bacteria that become exposed to the cytosol, and appear to coalesce on their hydrophobic surface leading to a transfer of diacylglycerol O-acyltransferase 2 (Dgat2)-GFP onto the bacteria. Dictyostelium knockout mutants for both Dgat enzymes are unable to generate LDs. Instead, the excess of exogenous FAs is esterified predominantly into phospholipids, inducing uncontrolled proliferation of the endoplasmic reticulum (ER). Strikingly, in absence of host LDs, M. marinum alternatively exploits these phospholipids, resulting in rapid reversal of ER-proliferation. In addition, the bacteria are unable to restrict their acquisition of lipids from the dgat1&2 double knockout leading to vast accumulation of ILIs. Recent data indicate that the presence of ILIs is one of the characteristics of dormant mycobacteria. During Dictyostelium infection, ILI formation in M. marinum is not accompanied by a significant change in intracellular growth and a reduction in metabolic activity, thus providing evidence that storage of neutral lipids does not necessarily induce dormancy.

  12. Mycobacterium marinum Degrades Both Triacylglycerols and Phospholipids from Its Dictyostelium Host to Synthesise Its Own Triacylglycerols and Generate Lipid Inclusions.

    Directory of Open Access Journals (Sweden)

    Caroline Barisch

    2017-01-01

    Full Text Available During a tuberculosis infection and inside lipid-laden foamy macrophages, fatty acids (FAs and sterols are the major energy and carbon source for Mycobacterium tuberculosis. Mycobacteria can be found both inside a vacuole and the cytosol, but how this impacts their access to lipids is not well appreciated. Lipid droplets (LDs store FAs in form of triacylglycerols (TAGs and are energy reservoirs of prokaryotes and eukaryotes. Using the Dictyostelium discoideum/Mycobacterium marinum infection model we showed that M. marinum accesses host LDs to build up its own intracytosolic lipid inclusions (ILIs. Here, we show that host LDs aggregate at regions of the bacteria that become exposed to the cytosol, and appear to coalesce on their hydrophobic surface leading to a transfer of diacylglycerol O-acyltransferase 2 (Dgat2-GFP onto the bacteria. Dictyostelium knockout mutants for both Dgat enzymes are unable to generate LDs. Instead, the excess of exogenous FAs is esterified predominantly into phospholipids, inducing uncontrolled proliferation of the endoplasmic reticulum (ER. Strikingly, in absence of host LDs, M. marinum alternatively exploits these phospholipids, resulting in rapid reversal of ER-proliferation. In addition, the bacteria are unable to restrict their acquisition of lipids from the dgat1&2 double knockout leading to vast accumulation of ILIs. Recent data indicate that the presence of ILIs is one of the characteristics of dormant mycobacteria. During Dictyostelium infection, ILI formation in M. marinum is not accompanied by a significant change in intracellular growth and a reduction in metabolic activity, thus providing evidence that storage of neutral lipids does not necessarily induce dormancy.

  13. Energy storage

    Science.gov (United States)

    Kaier, U.

    1981-04-01

    Developments in the area of energy storage are characterized, with respect to theory and laboratory, by an emergence of novel concepts and technologies for storing electric energy and heat. However, there are no new commercial devices on the market. New storage batteries as basis for a wider introduction of electric cars, and latent heat storage devices, as an aid for solar technology applications, with satisfactory performance standards are not yet commercially available. Devices for the intermediate storage of electric energy for solar electric-energy systems, and for satisfying peak-load current demands in the case of public utility companies are considered. In spite of many promising novel developments, there is yet no practical alternative to the lead-acid storage battery. Attention is given to central heat storage for systems transporting heat energy, small-scale heat storage installations, and large-scale technical energy-storage systems.

  14. Cinnamon polyphenols regulate multiple metabolic pathways involved in intestinal lipid metabolism of primary small intestinal enterocytes

    Science.gov (United States)

    Increasing evidence suggests that dietary factors may affect the expression of multiple genes and signaling pathways including those that regulate intestinal lipoprotein metabolism. The small intestine is actively involved in the regulation of dietary lipid absorption, intracellular transport and me...

  15. Membrane contact sites, ancient and central hubs of cellular lipid logistics

    NARCIS (Netherlands)

    Jain, Amrita; Holthuis, Joost C.M.

    2017-01-01

    Membrane contact sites (MCSs) are regions where two organelles are closely apposed to facilitate molecular communication and promote a functional integration of compartmentalized cellular processes. There is growing evidence that MCSs play key roles in controlling intracellular lipid flows and

  16. Intracellular ion channels and cancer

    Directory of Open Access Journals (Sweden)

    Luigi eLeanza

    2013-09-01

    Full Text Available Several types of channels play a role in the maintenance of ion homeostasis in subcellular organelles including endoplasmatic reticulum, nucleus, lysosome, endosome and mitochondria. Here we give a brief overview of the contribution of various mitochondrial and other organellar channels to cancer cell proliferation or death. Much attention is focused on channels involved in intracellular calcium signaling and on ion fluxes in the ATP-producing organelle mitochondria. Mitochondrial K+ channels (Ca2+-dependent BKCa and IKCa, ATP-dependent KATP, Kv1.3, two-pore TWIK-related Acid-Sensitive K+ channel-3 (TASK-3, Ca2+ uniporter MCU, Mg2+-permeable Mrs2, anion channels (voltage-dependent chloride channel VDAC, intracellular chloride channel CLIC and the Permeability Transition Pore (MPTP contribute importantly to the regulation of function in this organelle. Since mitochondria play a central role in apoptosis, modulation of their ion channels by pharmacological means may lead to death of cancer cells. The nuclear potassium channel Kv10.1 and the nuclear chloride channel CLIC4 as well as the endoplasmatic reticulum (ER-located inositol 1,4,5-trisphosphate (IP3 receptor, the ER-located Ca2+ depletion sensor STIM1 (stromal interaction molecule 1, a component of the store-operated Ca2+ channel and the ER-resident TRPM8 are also mentioned. Furthermore, pharmacological tools affecting organellar channels and modulating cancer cell survival are discussed. The channels described in this review are summarized on Figure 1. Overall, the view is emerging that intracellular ion channels may represent a promising target for cancer treatment.

  17. 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.

  18. Energy storage

    International Nuclear Information System (INIS)

    2012-01-01

    After having outlined the importance of energy storage in the present context, this document outlines that it is an answer to economic, environmental and technological issues. It proposes a brief overview of the various techniques of energy storage: under the form of chemical energy (hydrocarbons, biomass, hydrogen production), thermal energy (sensitive or latent heat storage), mechanical energy (potential energy by hydraulic or compressed air storage, kinetic energy with flywheels), electrochemical energy (in batteries), electric energy (super-capacitors, superconductor magnetic energy storage). Perspectives are briefly evoked

  19. The FATP1-DGAT2 complex facilitates lipid droplet expansion at the ER-lipid droplet interface

    OpenAIRE

    Farese, Robert; Xu, N; Zhang, SO; Cole, RA; McKinney, SA; Guo, F; Haas, JT; Bobba, S; Farese, RV; Mak, HY

    2012-01-01

    At the subcellular level, fat storage is confined to the evolutionarily conserved compartments termed lipid droplets (LDs), which are closely associated with the endoplasmic reticulum (ER). However, the molecular mechanisms that enable ER-LD interaction an

  20. Squalestatin alters the intracellular trafficking of a neurotoxic prion peptide

    Directory of Open Access Journals (Sweden)

    Williams Alun

    2007-11-01

    Full Text Available Abstract Background Neurotoxic peptides derived from the protease-resistant core of the prion protein are used to model the pathogenesis of prion diseases. The current study characterised the ingestion, internalization and intracellular trafficking of a neurotoxic peptide containing amino acids 105–132 of the murine prion protein (MoPrP105-132 in neuroblastoma cells and primary cortical neurons. Results Fluorescence microscopy and cell fractionation techniques showed that MoPrP105-132 co-localised with lipid raft markers (cholera toxin and caveolin-1 and trafficked intracellularly within lipid rafts. This trafficking followed a non-classical endosomal pathway delivering peptide to the Golgi and ER, avoiding classical endosomal trafficking via early endosomes to lysosomes. Fluorescence resonance energy transfer analysis demonstrated close interactions of MoPrP105-132 with cytoplasmic phospholipase A2 (cPLA2 and cyclo-oxygenase-1 (COX-1, enzymes implicated in the neurotoxicity of prions. Treatment with squalestatin reduced neuronal cholesterol levels and caused the redistribution of MoPrP105-132 out of lipid rafts. In squalestatin-treated cells, MoPrP105-132 was rerouted away from the Golgi/ER into degradative lysosomes. Squalestatin treatment also reduced the association between MoPrP105-132 and cPLA2/COX-1. Conclusion As the observed shift in peptide trafficking was accompanied by increased cell survival these studies suggest that the neurotoxicity of this PrP peptide is dependent on trafficking to specific organelles where it activates specific signal transduction pathways.

  1. MR-Visible Lipids and the Tumor Microenvironment

    Science.gov (United States)

    Delikatny, E. James; Chawla, Sanjeev; Leung, Daniel-Joseph; Poptani, Harish

    2013-01-01

    MR-visible lipids or mobile lipids are defined as lipids that are observable using proton magnetic resonance spectroscopy in cells and in tissues. These MR-visible lipids are composed of triglycerides and cholesterol esters that accumulate in intracellular neutral lipid droplets, where their MR visibility is conferred as a result of the increased molecular motion available in this unique physical environment. This review will discuss factors that lead to the biogenesis of MR-visible lipids in cancer cells and in other cell types such as immune cells and fibroblasts. We focus on the accumulations of mobile lipids that are inducible in cultured cells by a number of stresses, including culture conditions and in response to activating stimuli or apoptotic cell death induced by anticancer drugs. This is compared with animal tumor models, where increases in mobile lipids are observed in response to chemo and radiotherapy, and to human tumors where mobile lipids are observed predominantly in high-grade brain tumors and in regions of necrosis. Conducive conditions for mobile lipid formation in the tumor microenvironment will be discussed including low pH, oxygen availability and the presence of inflammatory cells. It is concluded that MR-visible lipids appear in cancer cells and human tumors as a stress response. Mobile lipids stored as neutral lipid droplets may play a role in detoxification of the cell or act as an alternate energy source, especially in cancer cells, which often grow in ischemic/hypoxic environments. The role of MR-visible lipids in cancer diagnosis and assessment of treatment response both in animal models of cancer as well as human brain tumors will also be discussed. Although technical limitations exist in the accurate detection of intratumoral mobile lipids, early increases in mobile lipids after therapeutic interventions may be used as a potential biomarker for assessing treatment response in cancer. PMID:21538631

  2. NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus.

    Directory of Open Access Journals (Sweden)

    Onkar Sharma

    2016-03-01

    Full Text Available A global increase in invasive infections due to group A Streptococcus (S. pyogenes or GAS has been observed since the 1980s, associated with emergence of a clonal group of strains of the M1T1 serotype. Among other virulence attributes, the M1T1 clone secretes NAD+-glycohydrolase (NADase. When GAS binds to epithelial cells in vitro, NADase is translocated into the cytosol in a process mediated by streptolysin O (SLO, and expression of these two toxins is associated with enhanced GAS intracellular survival. Because SLO is required for NADase translocation, it has been difficult to distinguish pathogenic effects of NADase from those of SLO. To resolve the effects of the two proteins, we made use of anthrax toxin as an alternative means to deliver NADase to host cells, independently of SLO. We developed a novel method for purification of enzymatically active NADase fused to an amino-terminal fragment of anthrax toxin lethal factor (LFn-NADase that exploits the avid, reversible binding of NADase to its endogenous inhibitor. LFn-NADase was translocated across a synthetic lipid bilayer in vitro in the presence of anthrax toxin protective antigen in a pH-dependent manner. Exposure of human oropharyngeal keratinocytes to LFn-NADase in the presence of protective antigen resulted in cytosolic delivery of NADase activity, inhibition of protein synthesis, and cell death, whereas a similar construct of an enzymatically inactive point mutant had no effect. Anthrax toxin-mediated delivery of NADase in an amount comparable to that observed during in vitro infection with live GAS rescued the defective intracellular survival of NADase-deficient GAS and increased the survival of SLO-deficient GAS. Confocal microscopy demonstrated that delivery of LFn-NADase prevented intracellular trafficking of NADase-deficient GAS to lysosomes. We conclude that NADase mediates cytotoxicity and promotes intracellular survival of GAS in host cells.

  3. Effect of dietary vitamin E supplementation on lipid and colour ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-04-12

    Apr 12, 2010 ... Lipid and myoglobin oxidation are major causes of meat quality deterioration during storage of fresh chicken meat. Our objective is to determine the effects of dietary α-tocopherol supplementation on lipid and colour stability of fresh chicken thigh meat exposed in a supermarket shopwindow or stored in a.

  4. Anaerobic Digestion of Lipid-Rich Waste (online first)

    NARCIS (Netherlands)

    Cavaleiro, A.J.; Picavet, M.A.; Sousa, D.Z.; Stams, A.J.M.; Pereira, M.A.; Alves, M.M.

    2015-01-01

    Lipids present in waste and wastewater, also referred as fat, oil, and grease (FOG), can be efficiently converted to methane. This fact constitutes an opportunity for conserving the high energy content of waste lipids, thus facilitating its storage and future use as fuel, electricity, and heat. In

  5. Turning over a new leaf in lipid droplet biology

    Science.gov (United States)

    Lipid droplets (LDs) in plants have long been viewed as storage depots for neutral lipids that serve as energy sources or precursors for membrane biosynthesis. While much of our knowledge of LD function in plants comes from studies of oilseeds, a recent surge in research of LDs in non-seed tissues h...

  6. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa

    DEFF Research Database (Denmark)

    Blomberg Jensen, Martin; Bjerrum, Poul J; Jessen, Torben E

    2011-01-01

    BACKGROUND The vitamin D receptor (VDR) is expressed in human spermatozoa, and VDR-knockout mice and vitamin D (VD) deficiency in rodents results in impaired fertility, low sperm counts and a low number of motile spermatozoa. We investigated the role of activated VD (1,25(OH)(2)D(3)) in human...... spermatozoa and whether VD serum levels are associated with semen quality. METHODS Cross-sectional association study of semen quality and VD serum level in 300 men from the general population, and in vitro studies on spermatozoa from 40 men to investigate the effects of VD on intracellular calcium, sperm......M). 1,25(OH)(2)D(3) increased intracellular calcium concentration in human spermatozoa through VDR-mediated calcium release from an intracellular calcium storage, increased sperm motility and induced the acrosome reaction in vitro. CONCLUSIONS 1,25(OH)(2)D(3) increased intracellular calcium...

  7. 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 ...

  8. Altered dynamics of a lipid raft associated protein in a kidney model of Fabry disease.

    Science.gov (United States)

    Labilloy, Anatália; Youker, Robert T; Bruns, Jennifer R; Kukic, Ira; Kiselyov, Kirill; Halfter, Willi; Finegold, David; do Monte, Semiramis Jamil Hadad; Weisz, Ora A

    2014-02-01

    Accumulation of globotriaosylceramide (Gb3) and other neutral glycosphingolipids with galactosyl residues is the hallmark of Fabry disease, a lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A (α-gal A). These lipids are incorporated into the plasma membrane and intracellular membranes, with a preference for lipid rafts. Disruption of raft mediated cell processes is implicated in the pathogenesis of several human diseases, but little is known about the effects of the accumulation of glycosphingolipids on raft dynamics in the context of Fabry disease. Using siRNA technology, we have generated a polarized renal epithelial cell model of Fabry disease in Madin-Darby canine kidney cells. These cells present increased levels of Gb3 and enlarged lysosomes, and progressively accumulate zebra bodies. The polarized delivery of both raft-associated and raft-independent proteins was unaffected by α-gal A knockdown, suggesting that accumulation of Gb3 does not disrupt biosynthetic trafficking pathways. To assess the effect of α-gal A silencing on lipid raft dynamics, we employed number and brightness (N&B) analysis to measure the oligomeric status and mobility of the model glycosylphosphatidylinositol (GPI)-anchored protein GFP-GPI. We observed a significant increase in the oligomeric size of antibody-induced clusters of GFP-GPI at the plasma membrane of α-gal A silenced cells compared with control cells. Our results suggest that the interaction of GFP-GPI with lipid rafts may be altered in the presence of accumulated Gb3. The implications of our results with respect to the pathogenesis of Fabry disease are discussed. © 2013 Elsevier Inc. All rights reserved.

  9. Cytoplasmic lipid bodies in eosinophils: Central roles in eicosanoid generation

    Directory of Open Access Journals (Sweden)

    Peter F Weller

    1997-01-01

    Full Text Available Lipid bodies are non-membrane bound, lipid-rich cytoplasmic inclusions that form in diverse cell types. Characteristically, lipid body numbers increase when eosinophils and other leukocytes are participating in inflammatory processes. Moreover, lipid bodies are numerous in other sites active in eicosanoid formation, such as the amnion epithelium at parturition. Our interests in lipid bodies relate to the roles that these structures play in arachidonate metabolism by eosinophils and other leukocytes involved in inflammation. Findings indicate that lipid bodies in these leukocytes can function as intracellular domains that are both depots of esterified arachidonate and sites at which regulated enzymatic events relevant to arachidonate metabolism can occur. Lipid bodies are discrete intracellular structures whose formation is specifically inducible early, whose increased numbers correlate with the 'priming' responses of leukocytes to form enhanced amounts of both cyclooxygenase- and lipoxygenase-derived eicosanoids and whose inhibition of formation correlates with reduced synthesis of these eicosanoids. Inhibition of lipid body formation represents a novel pharmacologic target to block the formation of eicosanoid mediators of inflammation.

  10. Energy storage

    International Nuclear Information System (INIS)

    Odru, P.

    2010-01-01

    This book proposes a broad overview of the technologies developed in the domains of on-board electricity storage (batteries, super-capacitors, flywheels), stationary storage (hydraulic dams, compressed air, batteries and hydrogen), and heat storage (sensible, latent and sorption) together with their relative efficiency, their expected developments and what advantages they can offer. Eminent specialists of this domain have participated to the redaction of this book, all being members of the Tuck's Foundation 'IDees' think tank. (J.S.)

  11. Energy storage

    CERN Document Server

    Brunet, Yves

    2013-01-01

    Energy storage examines different applications such as electric power generation, transmission and distribution systems, pulsed systems, transportation, buildings and mobile applications. For each of these applications, proper energy storage technologies are foreseen, with their advantages, disadvantages and limits. As electricity cannot be stored cheaply in large quantities, energy has to be stored in another form (chemical, thermal, electromagnetic, mechanical) and then converted back into electric power and/or energy using conversion systems. Most of the storage technologies are examined: b

  12. Tritium storage

    International Nuclear Information System (INIS)

    Hircq, B.

    1989-01-01

    A general synthesis about tritium storage is achieved in this paper and a particular attention is given to practical application in the Fusion Technology Program. Tritium, storage under gaseous form and solid form are discussed (characteristics, advantages, disadvantages and equipments). The way of tritium storage is then discussed and a choice established as a function of a logic which takes into account the main working parameters

  13. Pollen viability and membrane lipid composition

    NARCIS (Netherlands)

    Bilsen, van D.G.J.L.

    1993-01-01

    In this thesis membrane lipid composition is studied in relation to pollen viability during storage. Chapter 1 reviews pollen viability, membranes in the dry state and membrane changes associated with cellular aging. This chapter is followed by a study of age-related changes in phospholipid

  14. Ortholog-based screening and identification of genes related to intracellular survival.

    Science.gov (United States)

    Yang, Xiaowen; Wang, Jiawei; Bing, Guoxia; Bie, Pengfei; De, Yanyan; Lyu, Yanli; Wu, Qingmin

    2018-04-20

    Bioinformatics and comparative genomics analysis methods were used to predict unknown pathogen genes based on homology with identified or functionally clustered genes. In this study, the genes of common pathogens were analyzed to screen and identify genes associated with intracellular survival through sequence similarity, phylogenetic tree analysis and the λ-Red recombination system test method. The total 38,952 protein-coding genes of common pathogens were divided into 19,775 clusters. As demonstrated through a COG analysis, information storage and processing genes might play an important role intracellular survival. Only 19 clusters were present in facultative intracellular pathogens, and not all were present in extracellular pathogens. Construction of a phylogenetic tree selected 18 of these 19 clusters. Comparisons with the DEG database and previous research revealed that seven other clusters are considered essential gene clusters and that seven other clusters are associated with intracellular survival. Moreover, this study confirmed that clusters screened by orthologs with similar function could be replaced with an approved uvrY gene and its orthologs, and the results revealed that the usg gene is associated with intracellular survival. The study improves the current understanding of intracellular pathogens characteristics and allows further exploration of the intracellular survival-related gene modules in these pathogens. Copyright © 2018. Published by Elsevier B.V.

  15. MR imaging of intracellular and extracellular deoxyhemoglobin

    International Nuclear Information System (INIS)

    Janick, P.A.; Grossman, R.I.; Asakura, T.

    1989-01-01

    MR imaging was performed on varying concentrations of intracellular and extracellular deoxyhemoglobin as well as varying proportions of deoxyhemoglobin and oxyhemoglobin in vitro at 1.5T with use of standard spin-echo and gradient-refocused spin sequences. This study indicates that susceptibility-induced T2 shortening occurs over a broad range of intracellular deoxyhemoglobin concentrations (maximal at hematocrits between 20% and 45%), reflecting diffusional effects at the cellular level. T2* gradient-echo imaging enhances the observed hypointensity in images of intracellular deoxyhemoglobin. The characteristic MR appearance of acute hemotomas can be modeled by the behavior of intracellular and extracellular deoxyhemoglobin and oxyhemoglobin

  16. REAC technology as optimizer of stallion spermatozoa liquid storage.

    Science.gov (United States)

    Berlinguer, Fiammetta; Pasciu, Valeria; Succu, Sara; Cossu, Ignazio; Caggiu, Sabrina; Addis, Daniela; Castagna, Alessandro; Fontani, Vania; Rinaldi, Salvatore; Passino, Eraldo Sanna

    2017-02-08

    REAC technology (acronym for Radio Electric Asymmetric Conveyor) is a technology platform for neuro and bio modulation. It has already proven to optimize the ions fluxes at the molecular level and the molecular mechanisms driving cellular asymmetry and polarization. This study was designed to verify whether this technology could extend spermatozoa life-span during liquid storage, while preserving their functions, DNA integrity and oxidative status. At 0, 24, 48, and 72 h. of storage at 4 °C, a battery of analyses was performed to assess spermatozoa viability, motility parameters, acrosome status, and DNA integrity during REAC treatment. Spermatozoa oxidative status was assessed by determining lipid peroxidation, the activity of superoxide dismutase (SOD), and the total antioxidant capacity. During liquid storage REAC treated spermatozoa, while not showing an increased viability nor motility compared to untreated ones, had a higher acrosome (p > 0.001) and DNA integrity (p > 0.01). Moreover, the analysis of the oxidative status indicated that the mean activity of the intracellular superoxide dismutase (SOD) was significantly higher in REAC treated spermatozoa compared to untreated controls (p  0.05). The REAC efficacy on spermatozoa oxidative status was also evidenced by the higher trolox equivalent antioxidant capacity (TEAC) found in both the cellular extract (p spermatozoa compared to untreated controls (p spermatozoa acrosome membrane and DNA integrity, likely due to the enhancement of sperm antioxidant defenses. These results open new perspective about the extending of spermatozoa functions in vitro and the clinical management of male infertility.

  17. [Bioactive lipids in kidney physiology and pathophysiology].

    Science.gov (United States)

    Sałata, Daria; Dołęgowska, Barbara

    2014-01-24

    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.

  18. Microbial lipid production from SPORL-pretreated Douglas fir by Mortierella isabellina

    Science.gov (United States)

    S.M. Harde; Z. Wang; M. Horne; Junyong Zhu; X. Pan

    2016-01-01

    The solid substrate and spent liquo robtained after SPORL pretreatment of Douglas fir residues were evaluated as substrates for the production of intracellular microbial lipid by Mortierella isabellina NRRL 1757. The production of lipid was investigated in a batch fermentation using different strategies viz. separate hydrolysis...

  19. Oxidative deterioration of pork during superchilling storage.

    Science.gov (United States)

    Pomponio, Luigi; Ruiz-Carrascal, Jorge

    2017-12-01

    In superchilling (SC), meat is kept at temperatures around 1 °C below its initial freezing point, leading to a significant increase in shelf life. This study aimed to address the oxidative changes taking place in pork loins during prolonged storage at SC temperature. Loins were stored either at chilling (CH) conditions (2-4 °C) for 4 weeks or at SC temperature (around -1 °C) for 12 weeks. Storage at SC temperature diminished the rate of lipid and protein oxidation and discoloration in pork loins, so that final levels of most oxidation products and instrumental color values after 12 weeks of SC storage were similar to those after 4 weeks at CH conditions. However, hexanal content peaked by the end of SC storage, pointing to a potential accumulation of compounds from lipid oxidation during SC storage. SC storage of pork slows down the rate of lipid and protein oxidation. However, accumulation of volatile compounds from lipid oxidation could be a limiting factor for shelf life. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  20. 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.

  1. Storage rings

    Energy Technology Data Exchange (ETDEWEB)

    O' Neill, Gerald K.

    1963-04-15

    The development of storage rings is discussed. Advantages of such devices are pointed out as well as their limits, requirements, and design and fabrication problems. Information gained by the operation of small electron storage rings is included, and three experiments are proposed for colliding-beam facilities. (D.C.W.)

  2. Study of the effects of gamma radiation on the microbiological quality, lipid oxidation and sensory properties of mechanically deboned chicken meat throughout refrigerated and frozen storage; Estudo dos efeitos da radiacao gama sobre a qualidade microbiologica, a oxidacao lipidica e as propriedades sensoriais da carne mecanicamente separada de frango, armazenada refrigerada e congelada

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Heliana de Azevedo

    2002-07-01

    Mechanically deboned chicken meat (MDCM) is widely used in traditional meat products such as sausages. The proceed of mechanical separation results in grinding of the bones, liberating the marrow and rupturing cells, thus making the MDCM a favorable medium for biochemical reactions and microbiological growth. Irradiation using a Co{sup 60} source is one of the processes which has been developed aimed at reducing contamination by spoilage and pathogenic microorganisms in foods. The main advantages of food irradiation are the possibilities of treating the already packaged products at refrigerated and frozen temperatures, ideal for a highly perishable product such as MDCM, which, being a ground, easily spoiled product, requires rapid cooling followed by freezing, immediately after processing. Processing with ionizing radiation results in chemical alterations in the food, including the production of volatile compounds and free radicals. Irradiation of meat in the frozen state reduces or eliminates the negative sensory effects of this process. In this context, this study aimed at evaluating the effects of gamma radiation at doses of 3.0 and 4.0 kGy, on the microbiological quality, lipid oxidation and sensory properties of MDCM, at the refrigerated (2 {+-} 1 deg C) and frozen (-18 {+-} 1 deg C) storage, The results showed that irradiation increased the shelf life of this raw material when stored under refrigeration, as compared to non-irradiated samples. Since doses of 3.0 kGy produced increases in the shelf life of refrigerated MDCM equal or greater than those produced by doses of 4.0 kGy, this dose was considered the most adequate for the irradiation of this raw material. According to the results of microbiological, chemical and sensorial testing in irradiated MDCM samples with doses of 3.0 kGy and 4.0 kGy, the material studied presented conditions that were adequate for human consumption during the 90 days of frozen storage, whereas samples of non-irradiated MDCM were

  3. 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....

  4. Cellular effects of fluorodeoxyglucose: Global changes in the lipidome and alteration in intracellular transport.

    Science.gov (United States)

    Kavaliauskiene, Simona; Torgersen, Maria Lyngaas; Lingelem, Anne Berit Dyve; Klokk, Tove Irene; Lintonen, Tuulia; Simolin, Helena; Ekroos, Kim; Skotland, Tore; Sandvig, Kirsten

    2016-11-29

    2-fluoro-2-deoxy-D-glucose (FDG), labeled with 18F radioisotope, is the most common imaging agent used for positron emission tomography (PET) in oncology. However, little is known about the cellular effects of FDG. Another glucose analogue, 2-deoxy-D-glucose (2DG), has been shown to affect many cellular functions, including intracellular transport and lipid metabolism, and has been found to improve the efficacy of cancer chemotherapeutic agents in vivo. Thus, in the present study, we have investigated cellular effects of FDG with the focus on changes in cellular lipids and intracellular transport. By quantifying more than 200 lipids from 17 different lipid classes in HEp-2 cells and by analyzing glycosphingolipids from MCF-7, HT-29 and HBMEC cells, we have discovered that FDG treatment inhibits glucosylceramide synthesis and thus reduces cellular levels of glycosphingolipids. In addition, in HEp-2 cells the levels and/or species composition of other lipid classes, namely diacylglycerols, phosphatidic acids and phosphatidylinositols, were found to change upon treatment with FDG. Furthermore, we show here that FDG inhibits retrograde Shiga toxin transport and is much more efficient in protecting cells against the toxin than 2DG. In summary, our data reveal novel effects of FDG on cellular transport and glycosphingolipid metabolism, which suggest a potential clinical application of FDG as an adjuvant for cancer chemotherapy.

  5. Lipid accumulation and alkaline phosphatase activity in human ...

    African Journals Online (AJOL)

    Background: Alkaline phosphatase (ALP) controls intracellular lipid accumulation in human preadipocytes, but it is not known whether ALP is expressed in all body fat depots, or whether it has a similar role at all sites. Design: Cross-sectional. Setting and subjects: Subjects undergoing breast reduction and abdominal fat ...

  6. Lipid accumulation and alkaline phosphatase activity in human ...

    African Journals Online (AJOL)

    2012-10-03

    Oct 3, 2012 ... Background: Alkaline phosphatase (ALP) controls intracellular lipid accumulation in human preadipocytes, but it is not known whether ALP .... glutamine, supplemented with 10% foetal bovine serum and 100 U/ml penicillin ..... by a cascade of transcription factor gene expression.34. Evidence that ALP acts ...

  7. Serum Calcium Level is Associated with Lipids in Young Nigerian ...

    African Journals Online (AJOL)

    associated with high blood pressure in a representative sample of United States of American adults without cardiovascular diseases (CVDs) which was independent of age, sex, race, alcohol, smoking, diabetes, lipids, serum albumin, serum vitamin D and phosphorus.[23]. Calcium is an important intracellular messenger ...

  8. Efficient liposome fusion mediated by lipid-nucleic acid conjugates

    DEFF Research Database (Denmark)

    Ries, O; Löffler, P M G; Rabe, A

    2017-01-01

    The fusion of biomembranes with release of encapsulated content in a controlled way is crucial for cell signaling, endo- and exocytosis and intracellular trafficking. Programmable fusion of liposomes and an efficient mixing of their contents have the potential to enable the study of chemical...... and enzymatic processes in a confined environment and under crowded conditions outside biological systems. We report on DNA-controlled fusion of lipid bilayer membranes using lipid-nucleic acid conjugates (LiNAs) to mediate lipid and content mixing of liposomes. Screening of different membrane anchor and linker...

  9. Intracellular Polyamines Enhance Astrocytic Coupling

    Science.gov (United States)

    Benedikt, Jan; Inyushin, Mikhail; Kucheryavykh, Yuriy V.; Rivera, Yomarie; Kucheryavykh, Lilia Y.; Nichols, Colin G.; Eaton, Misty J.; Skatchkov, Serguei N.

    2013-01-01

    Spermine (SPM) and spermidine (SPD), endogenous polyamines (PA) with the ability to modulate various ion channels and receptors in the brain, exert neuroprotective, antidepressant, antioxidant and other effects in vivo such as increasing longevity. These PA are preferably accumulated in astrocytes, and we hypothesized that SPM increases glial intercellular communication by interacting with glial gap junctions. Results obtained in situ, using Lucifer yellow propagation in the astrocytic syncitium of 21–25 day old rat CA1 hippocampal slices, showed reduced coupling when astrocytes were dialyzed with standard intracellular solutions (ICS) without SPM. However, there was a robust increase in the spreading of Lucifer yellow via gap junctions to neighboring astrocytes when the cells were patched with ICS containing 1 mM SPM; a physiological concentration in glia. Lucifer yellow propagation was inhibited by gap junction blockers. Our findings show that the glial syncitium propagates SPM via gap junctions and further suggest a new role of polyamines in the regulation of the astroglial network in both normal and pathological conditions. PMID:23076119

  10. Fluorophore-tagged pharmacophores for antitumor cytotoxicity: Modified chiral lipidic dialkynylcarbinols for cell imaging.

    Science.gov (United States)

    Listunov, Dymytrii; Mazères, Serge; Volovenko, Yulian; Joly, Etienne; Génisson, Yves; Maraval, Valérie; Chauvin, Remi

    2015-10-15

    Chiral lipidic dialkynylcarbinols (DACs), recently highlighted as antitumoral pharmacophores, have been conjugated to difluoroboron-dipyrromethene (bodipy), 7-hydroxy-coumarine, and 7-nitro-benzoxadiazole (NBD) fluorophore motifs through triazole clips. The labeled lipids preserve cytotoxic activity against HCT116 cells, and fluorescence microscopy of the stained cells showed clear signals in the intra-cellular membrane system. While the bodipy conjugate also labels lipid droplets very brightly, as expected, the coumarine and NBD probes appear as promising specific tools for the identification of the intra-cellular targets of DACs' cytotoxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Lipid droplet-associated proteins in alcoholic liver disease: a potential linkage with hepatocellular damage

    OpenAIRE

    Ikura, Yoshihiro; Caldwell, Stephen H

    2015-01-01

    Steatosis is a characteristic morphological change of alcoholic liver disease, but its pathologic significance is still obscure. Regardless of cell types, intracellular lipid droplets are coated with a phospholipid monolayer, on which many kinds of lipid droplet-associated proteins are present. These proteins, such as the perilipin family of proteins and the cell death inducing DNA fragmentation factor (DFF) 45-like effectors, are recognized to play important roles in lipid metabolism in the ...

  12. Optimization of cationic lipid mediated gene transfer: structure-function, physico-chemical, and cellular studies.

    Science.gov (United States)

    Carrière, Marie; Tranchant, Isabelle; Niore, Pierre-Antoine; Byk, Gerardo; Mignet, Nathalie; Escriou, Virginie; Scherman, Daniel; Herscovici, Jean

    2002-01-01

    The rationale design aimed at the enhancement of cationic lipid mediated gene transfer is discussed. These improvements are based on the straight evaluation of the structure-activity relationship and on the introduction of new structures. Much attention have been given to the supramolecular structures of the lipid/DNA complexes, to the effect of serum on gene transfer and to the intracellular trafficking of the lipoplexes. Finally new avenue using reducible cationic lipids has been discussed.

  13. Imaging lipid metabolism in live Caenorhabditis elegans using fingerprint vibrations.

    Science.gov (United States)

    Wang, Ping; Liu, Bin; Zhang, Delong; Belew, Micah Y; Tissenbaum, Heidi A; Cheng, Ji-Xin

    2014-10-27

    Quantitation of lipid storage, unsaturation, and oxidation in live C. elegans has been a long-standing obstacle. The combination of hyperspectral stimulated Raman scattering imaging and multivariate analysis in the fingerprint vibration region represents a platform that allows the quantitative mapping of fat distribution, degree of fat unsaturation, lipid oxidation, and cholesterol storage in vivo in the whole worm. Our results reveal for the first time that lysosome-related organelles in intestinal cells are sites for storage of cholesterol in C. elegans. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Variety in intracellular diffusion during the cell cycle

    DEFF Research Database (Denmark)

    Selhuber-Unkel, C.; Yde, P.; Berg-Sørensen, Kirstine

    2009-01-01

    Schizosaccharomyces Pombe using optical tweezers. The cell cycle was divided into interphase and mitotic cell division, and the mitotic cell division was further subdivided in its stages. During all stages of the cell cycle, the granules predominantly underwent subdiffusive motion, characterized by an exponent......During the cell cycle, the organization of the cytoskeletal network undergoes dramatic changes. In order to reveal possible changes of the viscoelastic properties in the intracellular space during the cell cycle we investigated the diffusion of endogenous lipid granules within the fission yeast...... a that is also linked to the viscoelastic moduli of the cytoplasm. The exponent a was significantly smaller during interphase than during any stage of the mitotic cell division, signifying that the cytoplasm was more elastic during interphase than during division. We found no significant differences...

  15. Intracellular pH in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Novak, I; Hug, M; Greger, R

    1997-01-01

    In order to study the mechanism of H+ and HCO3- transport in a HCO3- secreting epithelium, pancreatic ducts, we have measured the intracellular pH (pHi) in this tissue using the pH sensitive probe BCECF. We found that exposures of ducts to solutions containing acetate/acetic acid or NH4+/NH3...... buffers (20 mmol/l) led to pHi changes in accordance with entry of lipid-soluble forms of the buffers, followed by back-regulation of pHi by duct cells. In another type of experiment, changes in extracellular pH of solutions containing HEPES or HCO3-/CO2 buffers led to significant changes in pHi that did....... Under some conditions, these exchangers can be invoked to regulate cell pH....

  16. Intracellular calcium homeostasis and signaling.

    Science.gov (United States)

    Brini, Marisa; Calì, Tito; Ottolini, Denis; Carafoli, Ernesto

    2013-01-01

    Ca(2+) is a universal carrier of biological information: it controls cell life from its origin at fertilization to its end in the process of programmed cell death. Ca(2+) is a conventional diffusible second messenger released inside cells by the interaction of first messengers with plasma membrane receptors. However, it can also penetrate directly into cells to deliver information without the intermediation of first or second messengers. Even more distinctively, Ca(2+) can act as a first messenger, by interacting with a plasma membrane receptor to set in motion intracellular signaling pathways that involve Ca(2+) itself. Perhaps the most distinctive property of the Ca(2+) signal is its ambivalence: while essential to the correct functioning of cells, Ca(2+) becomes an agent that mediates cell distress, or even (toxic) cell death, if its concentration and movements inside cells are not carefully tuned. Ca(2+) is controlled by reversible complexation to specific proteins, which could be pure Ca(2+) buffers, or which, in addition to buffering Ca(2+), also decode its signal to pass it on to targets. The most important actors in the buffering of cell Ca(2+) are proteins that transport it across the plasma membrane and the membrane of the organelles: some have high Ca(2+) affinity and low transport capacity (e.g., Ca(2+) pumps), others have opposite properties (e.g., the Ca(2+) uptake system of mitochondria). Between the initial event of fertilization, and the terminal event of programmed cell death, the Ca(2+) signal regulates the most important activities of the cell, from the expression of genes, to heart and muscle contraction and other motility processes, to diverse metabolic pathways involved in the generation of cell fuels.

  17. Developmental regulation of intracellular calcium by N-methyl-D-aspartate and noradrenaline in rat visual cortex.

    Science.gov (United States)

    Kobayashi, M; Imamura, K; Kaub, P A; Nakadate, K; Watanabe, Y

    1999-01-01

    The effects of N-methyl-D-aspartate and noradrenaline on intracellular Ca2+ concentration in slices of rat visual cortex were studied using a fluorescent indicator, Fura-2. Bath application of N-methyl-D-aspartate (1-100 microM) increased intracellular Ca2+ concentration in a dose-dependent manner, especially in layers II/III. Noradrenaline (1-100 microM) also increased intracellular Ca2+ concentration in a dose-dependent manner, especially in layers I and IV. However, the maximum increase in intracellular Ca2+ concentration after 100 microM noradrenaline application was less than half of that after 100 microM N-methyl-D-aspartate application in slices obtained from animals in the sensitive period. The effect of noradrenaline was most prominent in slices of the sensitive period, whereas the N-methyl-D-aspartate-induced intracellular Ca2+ concentration response decreased with age. Additive effects from application of both N-methyl-D-aspartate and noradrenaline on intracellular Ca2+ concentration were found only in the neonatal stage. Pharmacological experiments showed that alpha1-adrenergic receptors play a major role in the noradrenaline-induced intracellular Ca2+ concentration response, although both alpha2- and beta-adrenergic receptors were also partially involved. The release of Ca2+ from intracellular storage underlay the early phase of the noradrenaline-induced intracellular Ca2+ concentration response, while extracellular Ca2+ influxes contributed to the sustained phase. Experiments using a gliotoxin, fluorocitric acid, suggested that the function of glial cells is involved in the noradrenaline-induced increase of intracellular Ca2+ concentration. The larger intracellular Ca2+ concentration response to noradrenaline during the sensitive period may modulate the increase in intracellular Ca2+ concentration by N-methyl-D-aspartate to maintain a higher level of cortical plasticity during this period.

  18. Adipocyte Differentiation-Related Protein and OXPAT in Rat and Human Skeletal Muscle: Involvement in Lipid Accumulation and Type 2 Diabetes Mellitus

    NARCIS (Netherlands)

    Minnaard, R.; Schrauwen, P.; Schaart, G.; Jorgensen, J.A.; Lenaers, E.; Mensink, M.R.; Hesselink, M.K.C.

    2009-01-01

    Setting: A disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin, adipocyte differentiation-related protein (ADRP), and TIP47] family have been shown to regulate lipid accumulation and intracellular metabolism

  19. Changes in lipids and fishy odour development in skin from Nile tilapia (Oreochromis niloticus) stored in ice.

    Science.gov (United States)

    Sae-Leaw, Thanasak; Benjakul, Soottawat; Gokoglu, Nalan; Nalinanon, Sitthipong

    2013-12-01

    Changes in lipids, lipoxygenase activity and fishy odour development in the skin of Nile tilapia (Oreochromis niloticus) during iced storage of 18 days were monitored. Triacylglycerol content of skin decreased with coincidental increases in free fatty acid, monoacylglycerol, diacylglycerol and phospholipid contents during storage (pskin was observed as the storage time increased. The development of fishy odour in Nile tilapia skin during iced storage was mostly governed by lipid oxidation via autoxidation or induced by lipoxygenase. Thus, the extended storage time of whole fish resulted in the pronounced changes in lipids and the increased fishy odour in the skin. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Eps15: a multifunctional adaptor protein regulating intracellular trafficking

    Directory of Open Access Journals (Sweden)

    van Bergen en Henegouwen Paul MP

    2009-10-01

    Full Text Available Abstract Over expression of receptor tyrosine kinases is responsible for the development of a wide variety of malignancies. Termination of growth factor signaling is primarily determined by the down regulation of active growth factor/receptor complexes. In recent years, considerable insight has been gained in the endocytosis and degradation of growth factor receptors. A crucial player in this process is the EGFR Protein tyrosine kinase Substrate #15, or Eps15. This protein functions as a scaffolding adaptor protein and is involved both in secretion and endocytosis. Eps15 has been shown to bind to AP-1 and AP-2 complexes, to bind to inositol lipids and to several other proteins involved in the regulation of intracellular trafficking. In addition, Eps15 has been detected in the nucleus of mammalian cells. Activation of growth factor receptors induces tyrosine phosphorylation and mono-ubiquitination of Eps15. The role of these post translational modifications of Eps15 is still a mystery. It is proposed that Eps15 and its family members Eps15R and Eps15b are involved in the regulation of membrane morphology, which is required for intracellular vesicle formation and trafficking.

  1. Crystallographic study of FABP5 as an intracellular endocannabinoid transporter

    Energy Technology Data Exchange (ETDEWEB)

    Sanson, Benoît; Wang, Tao [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Sun, Jing; Wang, Liqun; Kaczocha, Martin [Stony Brook University, Stony Brook, NY 11794-5213 (United States); Ojima, Iwao [Stony Brook University, Stony Brook, NY 1794-3400 (United States); Stony Brook University, Stony Brook, NY 11794-3400 (United States); Deutsch, Dale, E-mail: dale.deutsch@stonybrook.edu [Stony Brook University, Stony Brook, NY 11794-5213 (United States); Stony Brook University, Stony Brook, NY 11794-3400 (United States); Li, Huilin, E-mail: dale.deutsch@stonybrook.edu [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Stony Brook University, Stony Brook, NY 11794-5213 (United States); Stony Brook University, Stony Brook, NY 11794-3400 (United States)

    2014-02-01

    FABP5 was recently found to intracellularly transport endocannabinoid signaling lipids. The structures of FABP5 complexed with two endocannabinoids and an inhibitor were solved. Human FABP5 was found to dimerize via a domain-swapping mechanism. This work will help in the development of inhibitors to raise endocannabinoid levels. In addition to binding intracellular fatty acids, fatty-acid-binding proteins (FABPs) have recently been reported to also transport the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), arachidonic acid derivatives that function as neurotransmitters and mediate a diverse set of physiological and psychological processes. To understand how the endocannabinoids bind to FABPs, the crystal structures of FABP5 in complex with AEA, 2-AG and the inhibitor BMS-309403 were determined. These ligands are shown to interact primarily with the substrate-binding pocket via hydrophobic interactions as well as a common hydrogen bond to the Tyr131 residue. This work advances our understanding of FABP5–endocannabinoid interactions and may be useful for future efforts in the development of small-molecule inhibitors to raise endocannabinoid levels.

  2. The effect of intracellular trafficking of CD1d on the formation of TCR repertoire of NKT cells.

    Science.gov (United States)

    Shin, Jung Hoon; Park, Se-Ho

    2014-05-01

    CD1 molecules belong to non-polymorphic MHC class I-like proteins and present lipid antigens to T cells. Five different CD1 genes (CD1a-e) have been identified and classified into two groups. Group 1 include CD1a-c and present pathogenic lipid antigens to αβ T cells reminiscence of peptide antigen presentation by MHC-I molecules. CD1d is the only member of Group 2 and presents foreign and self lipid antigens to a specialized subset of αβ T cells, NKT cells. NKT cells are involved in diverse immune responses through prompt and massive production of cytokines. CD1d-dependent NKT cells are categorized upon the usage of their T cell receptors. A major subtype of NKT cells (type I) is invariant NKT cells which utilize invariant Vα14-Jα18 TCR alpha chain in mouse. The remaining NKT cells (type II) utilize diverse TCR alpha chains. Engineered CD1d molecules with modified intracellular trafficking produce either type I or type II NKT cell-defects suggesting the lipid antigens for each subtypes of NKT cells are processed/generated in different intracellular compartments. Since the usage of TCR by a T cell is the result of antigen-driven selection, the intracellular metabolic pathways of lipid antigen are a key in forming the functional NKT cell repertoire.

  3. Influence of docosahexaenoic acid in vitro on intracellular adriamycin concentration in lymphocytes and human adriamycin-sensitive and -resistant small-cell lung cancer cell lines, and on cytotoxicity in the tumor cell lines

    NARCIS (Netherlands)

    Zijlstra, J G; de Vries, E G; Muskiet, F A; Martini, I A; Timmer-Bosscha, H; Mulder, N H

    1987-01-01

    An increase in the therapeutic effects of cancer chemotherapeutic agents and circumvention of drug resistance in cancer cells might result from an increase in the intracellular drug level. Alteration of the lipid domain of the cell membrane can result in a higher intracellular drug level. This

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

    Science.gov (United States)

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

    2014-02-01

    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 are suitable carriers for nucleic acids (DNA, siRNA). Considering the beneficial effect of helper lipids on the transfection efficiency with cationic liposomes, the effect of the helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) on transfection with cationic lipid-containing solid lipid nanoparticles was investigated in PC3 prostate cancer cells. The inclusion of DOPE in SLN formulations, instead of promoted, strongly inhibited SLN transfection efficiency, by frustrating the accommodation of DNA by the particles, as was revealed by biochemical analysis. SLNs devoid of DOPE maintained a homogenous size distribution of approximately 150 nm following lipoplex assembly and cellular delivery, and showed transfection efficiency comparable to that of Lipofectamine 2000' (LF2k). Moreover, the SLNs maintain their high transfection efficiency after lyophilization and long-term storage (1-2 years), an important asset for biomedical applications. There is even the possibility to lyophilize the SLN carrier together with its DNA cargo, which represents an interesting pharmaceutical advantage of the SLN formulations over LF2k. These results reflect marked differences between the physicochemical properties of cationic liposomes and SLNs, the latter requiring more critical lipid-depending properties for effective 'packaging' of DNA but displaying a higher storage stability than cationic lipid based carriers like LF2k.

  5. Altered lipid homeostasis in Drosophila InsP3 receptor mutants leads to obesity and hyperphagia

    Directory of Open Access Journals (Sweden)

    Manivannan Subramanian

    2013-05-01

    Obesity is a complex metabolic disorder that often manifests with a strong genetic component in humans. However, the genetic basis for obesity and the accompanying metabolic syndrome is poorly defined. At a metabolic level, obesity arises from an imbalance between the nutritional intake and energy utilization of an organism. Mechanisms that sense the metabolic state of the individual and convey this information to satiety centers help achieve this balance. Mutations in genes that alter or modify such signaling mechanisms are likely to lead to either obese individuals, who in mammals are at high risk for diabetes and cardiovascular disease, or excessively thin individuals with accompanying health problems. Here we show that Drosophila mutants for an intracellular calcium signaling channel, the inositol 1,4,5-trisphosphate receptor (InsP3R store excess triglycerides in their fat bodies and become unnaturally obese on a normal diet. Although excess insulin signaling can rescue obesity in InsP3R mutants to some extent, we show that it is not the only cause of the defect. Through mass spectrometric analysis of lipids we find that homeostasis of storage and membrane lipids are altered in InsP3R mutants. Possibly as a compensatory mechanism, InsP3R mutant adults also feed excessively. Thus, reduced InsP3R function alters lipid metabolism and causes hyperphagia in adults. Together, the metabolic and behavioral changes lead to obesity. Our results implicate altered InsP3 signaling as a previously unknown causative factor for metabolic syndrome in humans. Importantly, our studies also suggest preventive dietary interventions.

  6. Investigating Internalization and Intracellular Trafficking of GPCRs

    DEFF Research Database (Denmark)

    Foster, Simon R; Bräuner-Osborne, Hans

    2017-01-01

    for signal transduction. One of the major mechanisms for GPCR regulation involves their endocytic trafficking, which serves to internalize the receptors from the plasma membrane and thereby attenuate G protein-dependent signaling. However, there is accumulating evidence to suggest that GPCRs can signal...... independently of G proteins, as well as from intracellular compartments including endosomes. It is in this context that receptor internalization and intracellular trafficking have attracted renewed interest within the GPCR field. In this chapter, we will review the current understanding and methodologies...... that have been used to investigate internalization and intracellular signaling of GPCRs, with a particular focus on emerging real-time techniques. These recent developments have improved our understanding of the complexities of GPCR internalization and intracellular signaling and suggest that the broader...

  7. Nanoparticles for intracellular-targeted drug delivery

    International Nuclear Information System (INIS)

    Paulo, Cristiana S O; Pires das Neves, Ricardo; Ferreira, Lino S

    2011-01-01

    Nanoparticles (NPs) are very promising for the intracellular delivery of anticancer and immunomodulatory drugs, stem cell differentiation biomolecules and cell activity modulators. Although initial studies in the area of intracellular drug delivery have been performed in the delivery of DNA, there is an increasing interest in the use of other molecules to modulate cell activity. Herein, we review the latest advances in the intracellular-targeted delivery of short interference RNA, proteins and small molecules using NPs. In most cases, the drugs act at different cellular organelles and therefore the drug-containing NPs should be directed to precise locations within the cell. This will lead to the desired magnitude and duration of the drug effects. The spatial control in the intracellular delivery might open new avenues to modulate cell activity while avoiding side-effects.

  8. Energy storage cells

    Energy Technology Data Exchange (ETDEWEB)

    Gulia, N.V.

    1980-01-01

    The book deals with the characteristics and potentialities of energy storage cells of various types. Attention is given to electrical energy storage cells (electrochemical, electrostatic, and electrodynamic cells), mechanical energy storage cells (mechanical flywheel storage cells), and hybrid storage systems.

  9. Symbiodinium genotypic and environmental controls on lipids in reef building corals.

    Directory of Open Access Journals (Sweden)

    Timothy F Cooper

    Full Text Available BACKGROUND: Lipids in reef building corals can be divided into two classes; non-polar storage lipids, e.g. wax esters and triglycerides, and polar structural lipids, e.g. phospholipids and cholesterol. Differences among algal endosymbiont types are known to have important influences on processes including growth and the photobiology of scleractinian corals yet very little is known about the role of symbiont types on lipid energy reserves. METHODOLOGY/PRINCIPAL FINDINGS: The ratio of storage lipid and structural lipid fractions of Scott Reef corals were determined by thin layer chromatography. The lipid fraction ratio varied with depth and depended on symbiont type harboured by two corals (Seriatopora hystrix and Pachyseris speciosa. S. hystrix colonies associated with Symbiodinium C1 or C1/C# at deep depths (>23 m had lower lipid fraction ratios (i.e. approximately equal parts of storage and structural lipids than those with Symbiodinium D1 in shallow depths (<23 m, which had higher lipid fraction ratios (i.e. approximately double amounts of storage relative to structural lipid. Further, there was a non-linear relationship between the lipid fraction ratio and depth for S. hystrix with a modal peak at ∼23 m coinciding with the same depth as the shift from clade D to C types. In contrast, the proportional relationship between the lipid fraction ratio and depth for P. speciosa, which exhibited high specificity for Symbiodinium C3 like across the depth gradient, was indicative of greater amounts of storage lipids contained in the deep colonies. CONCLUSIONS/SIGNIFICANCE: This study has demonstrated that Symbiodinium exert significant controls over the quality of coral energy reserves over a large-scale depth gradient. We conclude that the competitive advantages and metabolic costs that arise from flexible associations with divergent symbiont types are offset by energetic trade-offs for the coral host.

  10. Control of intracellular heme levels: Heme transporters and Heme oxygenases

    Science.gov (United States)

    Khan, Anwar A.; Quigley, John G.

    2011-01-01

    Heme serves as a co-factor in proteins involved in fundamental biological processes including oxidative metabolism, oxygen storage and transport, signal transduction and drug metabolism. In addition, heme is important for systemic iron homeostasis in mammals. Heme has important regulatory roles in cell biology, yet excessive levels of intracellular heme are toxic; thus, mechanisms have evolved to control the acquisition, synthesis, catabolism and expulsion of cellular heme. Recently, a number of transporters of heme and heme synthesis intermediates have been described. Here we review aspects of heme metabolism and discuss our current understanding of heme transporters, with emphasis on the function of the cell-surface heme exporter, FLVCR. Knockdown of Flvcr in mice leads to both defective erythropoiesis and disturbed systemic iron homeostasis, underscoring the critical role of heme transporters in mammalian physiology. PMID:21238504

  11. 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.

  12. Effects of self-carbon dioxide-generation material for active packaging on pH, water-holding capacity, meat color, lipid oxidation and microbial growth in beef during cold storage.

    Science.gov (United States)

    Lee, Seung-Jae; Lee, Seung Yun; Kim, Gap-Don; Kim, Geun-Bae; Jin, Sang Keun; Hur, Sun Jin

    2017-08-01

    Active packaging refers to the mixing of additive agents into packaging materials with the purpose of maintaining or extending food product quality and shelf life. The aim of this study was to develop an easy and cheap active packaging for beef. Beef loin samples were divided into three packaging groups (C, ziplock bag packaging; T1, vacuum packaging; T2, active packaging) and stored at 4 °C for 21 days. The water-holding capacity was significantly (P packaging using self-CO 2 -generation materials can extend the shelf life similarly to that observed with vacuum packaging, and that the active packaging method can improve the quality characteristics of beef during cold storage. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  13. Dietary effects of oregano (Origanum vulgaris L. plant or sweet chestnut (Castanea sativa Mill. wood extracts on microbiological, chemical-physical characteristics and lipid oxidation of cooked ham during storage

    Directory of Open Access Journals (Sweden)

    David Ranucci

    2015-12-01

    Full Text Available The aim of this study was to evaluate the dietary effect of feeding pigs with diets enriched with sweet chestnut wood (Castanea sativa Mill. or oregano (Origanum vulgaris L. extract on the microbiological and chemical characteristics of cooked pork ham. Three groups of 10 pigs were fed with a control diet (CTRL, with the CTRL diet enriched with 0.2% of oregano extract (OR and with the CTRL diet enriched with 0.2% of sweet chestnut wood extract (SCW, respectively. Six cooked hams per group were produced, sliced and packaged under a modified atmosphere (N2:CO2=80:20 and stored at refrigeration temperature (4±1°C. Three packages per cooked ham were sampled for analyses at three different storage times (0, 10 and 20 days. At day 0 time, antioxidant capacity of the products (ORACFL assay and chemical composition were performed. At each sampling time, from all the samples the following analyses were performed: Total Microbial Count (TMC, Lactic Acid Bacteria count (LAB, Enterobacteriaceae count, Listeria monocytogenes, pH value, colour coordinates (L*, a*, b*, total basic volatile nitrogen (TBVN and thio-barbituric reactive substances (TBARs determinations. No differences in TMC, LAB and Enterobacteriaceae count, pH, TBVN, chemical composition and L* values were registered between the three groups at all the sampling times considered. No Listeria monocytogenes was detected in the samples tested. Significant differences were registered for ORACFL at 0 days, a* and b* values and TBARs value at 10 and 20 days of storage, with higher values for ORACFL, a* and b* values and lower values for TBARs in SCW and OR than CTRL. No antimicrobial effect could be recorded for OR and SCW but a higher oxidative stability, also highlighted by the colour maintenance, was observed in both OR and SCW.

  14. Dietary Effects of Oregano (Origanum Vulgaris L.) Plant or Sweet Chestnut (Castanea Sativa Mill.) Wood Extracts on Microbiological, Chemico-Physical Characteristics and Lipid Oxidation of Cooked ham During Storage.

    Science.gov (United States)

    Ranucci, David; Miraglia, Dino; Trabalza-Marinucci, Massimo; Acuti, Gabriele; Codini, Michela; Ceccarini, Maria Rachele; Forte, Claudio; Branciari, Raffaella

    2015-11-02

    The aim of this study was to evaluate the dietary effect of feeding pigs with diets enriched with sweet chestnut wood ( Castanea sativa Mill.) or oregano ( Origanum vulgaris L.) extract on the microbiological and chemical characteristics of cooked pork ham. Three groups of 10 pigs were fed with a control diet (CTRL), with the CTRL diet enriched with 0.2% of oregano extract (OR) and with the CTRL diet enriched with 0.2% of sweet chestnut wood extract (SCW), respectively. Six cooked hams per group were produced, sliced and packaged under a modified atmosphere (N2:CO2=80:20) and stored at refrigeration temperature (4±1°C). Three packages per cooked ham were sampled for analyses at three different storage times (0, 10 and 20 days). At day 0 time, antioxidant capacity of the products (ORAC FL assay) and chemical composition were performed. At each sampling time, from all the samples the following analyses were performed: total microbial count (TMC), lactic acid bacteria count (LAB), Enterobacteriaceae count, Listeria monocytogenes , pH value, colour coordinates (L*, a*, b*), total basic volatile nitrogen (TBVN) and thiobarbituric reactive substances (TBARs) determinations. No differences in TMC, LAB and Enterobacteriaceae count, pH, TBVN, chemical composition and L* values were registered between the three groups at all the sampling times considered. No Listeria monocytogenes was detected in the samples tested. Significant differences were registered for ORAC FL at 0 days, a* and b* values and TBARs value at 10 and 20 days of storage, with higher values for ORAC FL , a* and b* values and lower values for TBARs in SCW and OR than CTRL. No antimicrobial effect could be recorded for OR and SCW but a higher oxidative stability, also highlighted by the colour maintenance, was observed in both OR and SCW.

  15. Role of Diatoms in the Spatial-Temporal Distribution of Intracellular Nitrate in Intertidal Sediment

    DEFF Research Database (Denmark)

    Stief, P.; Kamp, A.; de Beer, D.

    2013-01-01

    Intracellular nitrate storage allows microorganisms to survive fluctuating nutrient availability and anoxic conditions in aquatic ecosystems. Here we show that diatoms, ubiquitous and highly abundant microalgae, represent major cellular reservoirs of nitrate in an intertidal flat of the German...... Wadden Sea and are potentially involved in anaerobic nitrate respiration. Intracellular nitrate (ICNO3) was present year-round in the sediment and was spatially and temporally correlated with fucoxanthin, the marker photopigment of diatoms. Pyrosequencing of SSU rRNA genes of all domains of life...... confirmed that ICNO3 storage was most likely due to diatoms rather than other known nitrate-storing microorganisms (i.e., large sulfur bacteria and the eukaryotic foraminifers and gromiids). Sedimentary ICNO3 concentrations reached up to 22.3 mu mol dm(-3) at the sediment surface and decreased with sediment...

  16. Type of dietary lipids and storing time on egg stability

    Directory of Open Access Journals (Sweden)

    Ana Lúcia Fernandes Pereira

    2011-12-01

    Full Text Available The objective of this work was to evaluate the influence of diets containing different lipid sources on eggs quality during refrigerated storage, on yolk fatty acid composition, and on cholesterol in the yolk. Four diets were used containing Soy Oil (SO, Sunflower Seed (SS, and Meat and Bone Meal + Soy Oil (MBM + SO or Meat and Bone Meal + Tallow (MBM + TA. The experiment followed a factorial design 4 × 3 with four dietary treatments and three storage times. The eggs were stored at 4 °C for 0, 30, and 60 days. The collected eggs were analyzed for egg weight loss, Haugh units, yolk moisture, yolk lipid oxidation, and cooked yolk firmness. Refrigerated storage reduced Haugh units, and increased yolk moisture. Sixty days of storage time reduced the firmness of hard-cooked yolk. There was an interaction between dietary treatment and storage time for egg weight loss and lipid oxidation. With regard to yolk fatty acid profile, MBM + TA diet increased the contents of palmitic and palmitoleic acids. The levels of oleic and arachidonic acids were higher in yolks from birds fed with SS diet. Linoleic acid level was higher in the yolk from treatment with SO diet. Diets containing MBM + SO induced higher levels of docosahexaenoic acid. Yolk cholesterol content was reduced with the inclusion of SS in the diet. Therefore, the type of lipid present in the diet and refrigerated storage for 60 days at 4 °C can affect the egg quality.

  17. The decompensated detrusor I: the effects of bladder outlet obstruction on the use of intracellular calcium stores.

    Science.gov (United States)

    Rohrmann, D; Levin, R M; Duckett, J W; Zderic, S A

    1996-08-01

    As in other smooth muscle groups, extracellular calcium influx as well as the release of calcium from intracellular storage sites or sarcoplasmic reticulum occur in response to receptor stimulation. The relative participation of extracellular influx versus intracellular release has recently been shown to be influenced by developmental stage and obstruction. Partial bladder outlet obstruction results in marked hypertrophy of the bladder and produces alterations in contractile function. To understand better how this contractile dysfunction after outlet obstruction is influenced by intracellular calcium handling we tested the effects of 2 drugs with known effects on the sarcoplasmic reticulum. We evaluated ryanodine, which blocks the release of calcium from the sarcoplasmic reticulum, and thapsigargin, which blocks the ability of the sarcoplasmic reticulum to pump cytosolic calcium back into the storage sites. Rabbit bladders were obstructed for different periods, after which detrusor muscle strips were harvested and contractile performance was evaluated in the absence and presence of ryanodine and thapsigargin. In the early phases of outlet obstruction the release of intracellular calcium increased significantly. With prolonged obstruction and detrusor decompensation the intracellular storage sites lost the ability to contribute to the generation of contractile force. Alterations in the calcium handling ability of the smooth muscle cell appear to have an important role in the process of decompensation of bladder function in infravesical obstruction.

  18. Energy storage

    International Nuclear Information System (INIS)

    Hermans, J.H.W.E.

    1998-01-01

    A brief overview is given of the research activities of the Dutch association for energy distribution companies EnergieNed in the field of energy storage techniques, carried out within the framework of the long-range programme Study and Research (MSO, abbreviated in Dutch)

  19. Dry storage

    International Nuclear Information System (INIS)

    Arnott, Don.

    1985-01-01

    The environmental movement has consistently argued against disposal of nuclear waste. Reasons include its irretrievability in the event of leakage, the implication that reprocessing will continue and the legitimacy attached to an expanding nuclear programme. But there is an alternative. The author here sets out the background and a possible future direction of a campaign based on a call for dry storage. (author)

  20. 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. Sociedad Argentina de Pediatría.

  1. 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...

  2. Insuficiências respiratória e renal desencadeadas por miopatia metabólica por acúmulo de lipídios: relato de caso Respiratory and renal dysfunctions due to lipid storage metabolic myopathy: case report

    Directory of Open Access Journals (Sweden)

    Walther de Oliveira Campos Filho

    2002-09-01

    Full Text Available Relatamos o caso de um paciente de 26 anos que apresentou quadro clínico de rabdomiólise e mioglobinúria associadas a insuficiência renal e respiratória, três dias após o início de infecção de vias aéreas superiores. Os dados clínicos e laboratoriais, eletroneuromiografia e biópsia muscular conduziram ao diagnóstico de miopatia metabólica por deficiência enzimática relacionada ao metabolismo dos ácidos graxos. O paciente evoluiu favoravelmente com a instituição de suporte avançado de vida, incluindo assistência ventilatória e terapia dialítica, adequação dietética e reposição de L-carnitina. Discorremos sobre as diversas miopatias metabólicas, o diagnóstico, o diagnóstico diferencial e o tratamento.We report a case of a 26-years old male patient with rhabdomyolisis with myoglobinuria associated with acute renal and respiratory failure, that occurred three days after upper airway infection. In the clinical and laboratory investigation of the patient, including electromyography and muscular biopsy, the diagnostic lead to a metabolic myopathy due to an enzymatic deficiency related to a disorder of lipid metabolism. The patient improved successfully with institution of advanced life support, including ventilatory assistence, dialysis, dietary adjust and L-carnitine reposition.

  3. A Role of Lipid Metabolism during Cumulus-Oocyte Complex Maturation: Impact of Lipid Modulators to Improve Embryo Production

    Directory of Open Access Journals (Sweden)

    E. G. Prates

    2014-01-01

    Full Text Available Oocyte intracellular lipids are mainly stored in lipid droplets (LD providing energy for proper growth and development. Lipids are also important signalling molecules involved in the regulatory mechanisms of maturation and hence in oocyte competence acquisition. Recent studies show that LD are highly dynamic organelles. They change their shape, volume, and location within the ooplasm as well as their interaction with other organelles during the maturation process. The droplets high lipid content has been correlated with impaired oocyte developmental competence and low cryosurvival. Yet the underlying mechanisms are not fully understood. In particular, the lipid-rich pig oocyte might be an excellent model to understand the role of lipids and fatty acid metabolism during the mammalian oocyte maturation and their implications on subsequent monospermic fertilization and preimplantation embryo development. The possibility of using chemical molecules to modulate the lipid content of oocytes and embryos to improve cryopreservation as well as its biological effects during development is here described. Furthermore, these principles of lipid content modulation may be applied not only to germ cells and embryo cryopreservation in livestock production but also to biomedical fundamental research.

  4. Micro- and nanotechnologies for intracellular delivery.

    Science.gov (United States)

    Yan, Li; Zhang, Jinfeng; Lee, Chun-Sing; Chen, Xianfeng

    2014-11-01

    The majority of drugs and biomolecules need to be delivered into cells to be effective. However, the cell membranes, a biological barrier, strictly resist drugs or biomolecules entering cells, resulting in significantly reduced intracellular delivery efficiency. To overcome this barrier, a variety of intracellular delivery approaches including chemical and physical ways have been developed in recent years. In this review, the focus is on summarizing the nanomaterial routes involved in making use of a collection of receptors for the targeted delivery of drugs and biomolecules and the physical ways of applying micro- and nanotechnologies for high-throughput intracellular delivery. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Fluorescent nanothermometers for intracellular thermal sensing.

    Science.gov (United States)

    Jaque, Daniel; Rosal, Blanca Del; Rodríguez, Emma Martín; Maestro, Laura Martínez; Haro-González, Patricia; Solé, José García

    2014-05-01

    The importance of high-resolution intracellular thermal sensing and imaging in the field of modern biomedicine has boosted the development of novel nanosized fluorescent systems (fluorescent nanothermometers) as the next generation of probes for intracellular thermal sensing and imaging. This thermal mapping requires fluorescent nanothermometers with good biocompatibility and high thermal sensitivity in order to obtain submicrometric and subdegree spatial and thermal resolutions, respectively. This review describes the different nanosized systems used up to now for intracellular thermal sensing and imaging. We also include the later advances in molecular systems based on fluorescent proteins for thermal mapping. A critical overview of the state of the art and the future perspective is also included.

  6. Underground Storage Tanks - Storage Tank Locations

    Data.gov (United States)

    NSGIC Education | GIS Inventory — A Storage Tank Location is a DEP primary facility type, and its sole sub-facility is the storage tank itself. Storage tanks are aboveground or underground, and are...

  7. Effect of training on muscle triacylglycerol and structural lipids

    DEFF Research Database (Denmark)

    Helge, Jørn W; Dela, Flemming

    2003-01-01

    We studied whether endurance training impacts insulin sensitivity by affecting the structural and storage lipids in humans. Eight male subjects participated (age 25 +/- 1 years, height 178 +/- 3 cm, weight 76 +/- 4 kg [mean +/- SE]). Single-leg training was performed for 30 min/day for 4 weeks...... polyunsaturates, which may indicate that membrane lipids may have a role in the training-induced increase in insulin sensitivity....

  8. Macrophage defense mechanisms against intracellular bacteria.

    Science.gov (United States)

    Weiss, Günter; Schaible, Ulrich E

    2015-03-01

    Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics. © 2015 The Authors

  9. Macrophage defense mechanisms against intracellular bacteria

    Science.gov (United States)

    Weiss, Günter; Schaible, Ulrich E

    2015-01-01

    Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics. PMID:25703560

  10. The non-peptidic part determines the internalization mechanism and intracellular trafficking of peptide amphiphiles.

    Science.gov (United States)

    Missirlis, Dimitris; Teesalu, Tambet; Black, Matthew; Tirrell, Matthew

    2013-01-01

    Peptide amphiphiles (PAs) are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications. PAs of a novel, cell- and tissue-penetrating peptide were synthesized possessing two different lipophilic tail architectures and their interactions with prostate cancer cells were studied in vitro. Cell uptake of peptides was greatly enhanced post-modification. Internalization occurred via lipid-raft mediated endocytosis and was common for the two analogs studied. On the contrary, we identified the non-peptidic part as the determining factor of differences between intracellular trafficking and retention of PAs. PAs composed of di-stearyl lipid tails linked through poly(ethylene glycol) to the peptide exhibited higher exocytosis rates and employed different recycling pathways compared to ones consisting of di-palmitic-coupled peptides. As a result, cell association of the former PAs decreased with time. Control over peptide intracellular localization and retention is possible by appropriate modification with synthetic hydrophobic tails. We propose this as a strategy to design improved peptide-based delivery systems.

  11. The non-peptidic part determines the internalization mechanism and intracellular trafficking of peptide amphiphiles.

    Directory of Open Access Journals (Sweden)

    Dimitris Missirlis

    Full Text Available BACKGROUND: Peptide amphiphiles (PAs are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications. METHODOLOGY/PRINCIPAL FINDINGS: PAs of a novel, cell- and tissue-penetrating peptide were synthesized possessing two different lipophilic tail architectures and their interactions with prostate cancer cells were studied in vitro. Cell uptake of peptides was greatly enhanced post-modification. Internalization occurred via lipid-raft mediated endocytosis and was common for the two analogs studied. On the contrary, we identified the non-peptidic part as the determining factor of differences between intracellular trafficking and retention of PAs. PAs composed of di-stearyl lipid tails linked through poly(ethylene glycol to the peptide exhibited higher exocytosis rates and employed different recycling pathways compared to ones consisting of di-palmitic-coupled peptides. As a result, cell association of the former PAs decreased with time. CONCLUSIONS/SIGNIFICANCE: Control over peptide intracellular localization and retention is possible by appropriate modification with synthetic hydrophobic tails. We propose this as a strategy to design improved peptide-based delivery systems.

  12. Role of intracellular infections in premature childbirth.

    Science.gov (United States)

    Zurabishvili, S; Mamamtavrishvili, I; Apridonidze, K; Shanidze, L

    2005-09-01

    Vaginal Smear taken by sterile Folkman spoon from 15 women with premature birth was studied. The study was performed by the direct immune fluorescence method with the luminescence microscope. We aimed to study the effect of intracellular infections: ureaplasma urealitikum, mycoplasma hominis, Chlamydia trachomatis, herpes simplex virus of I and II type and cytomegalovirus. Intracellular infections were detected in at about 82% of cases, which included mono infections with cytomegalovirus and in 9 cases in the form of bi-component associations. The obtained results may be interesting from the etiologic point of view of premature births in Georgian population.

  13. Epigenetic Modulation of the Biophysical Properties of Drug-Resistant Cell Lipids to Restore Drug Transport and Endocytic Functions

    OpenAIRE

    Vijayaraghavalu, Sivakumar; Peetla, Chiranjeevi; Lu, Shan; Labhasetwar, Vinod

    2012-01-01

    In our recent studies exploring the biophysical characteristics of resistant cell lipids, and the role they play in drug transport, we demonstrated the difference of drug-resistant breast cancer cells from drug-sensitive cells in lipid composition and biophysical properties, suggesting that cancer cells acquire a drug-resistant phenotype through the alteration of lipid synthesis to inhibit intracellular drug transport to protect from cytotoxic effect. In cancer cells, epigenetic changes (e.g....

  14. The Oleaginous Yeast Meyerozyma guilliermondii BI281A as a New Potential Biodiesel Feedstock: Selection and Lipid Production Optimization

    OpenAIRE

    Mauricio Ramírez-Castrillón; Mauricio Ramírez-Castrillón; Mauricio Ramírez-Castrillón; Victoria P. Jaramillo-Garcia; Priscila D. Rosa; Melissa F. Landell; Duong Vu; Mariana F. Fabricio; Marco A. Z. Ayub; Vincent Robert; João A. P. Henriques; Patricia Valente

    2017-01-01

    A high throughput screening (HTS) methodology for evaluation of cellular lipid content based on Nile red fluorescence reads using black background 96-wells test plates and a plate reader equipment allowed the rapid intracellular lipid estimation of strains from a Brazilian phylloplane yeast collection. A new oleaginous yeast, Meyerozyma guilliermondii BI281A, was selected, for which the gravimetric determination of total lipids relative to dry weight was 52.38% for glucose or 34.97% for pure ...

  15. siRNA delivery with lipid-based systems

    DEFF Research Database (Denmark)

    Foged, Camilla

    2012-01-01

    in vivo, toxicity and non-specific stimulation of the immune system. To optimally design and tailor the lipidic systems for siRNA delivery, better insight is needed into the mechanisms of cell delivery. More specifically, further clarification is need regarding the nature of cell surface interactions......, routes of internalization, passage of intracellular membranes, and mechanisms of immune activation. This review provides an overview of the main constituents currently employed in lipid-based siRNA carriers, and recent research into improvements of cell delivery. In addition, pitfalls related to immune...

  16. Recovery of Fuel-Precursor Lipids from Oleaginous Yeast

    Energy Technology Data Exchange (ETDEWEB)

    Kruger, Jacob S. [National Bioenergy Center, National Renewable Energy Laboratory, 15013 Denver West Parkway, Golden, Colorado 80401, United States; Cleveland, Nicholas S. [National Bioenergy Center, National Renewable Energy Laboratory, 15013 Denver West Parkway, Golden, Colorado 80401, United States; Yeap, Rou Yi [National Bioenergy Center, National Renewable Energy Laboratory, 15013 Denver West Parkway, Golden, Colorado 80401, United States; Dong, Tao [National Bioenergy Center, National Renewable Energy Laboratory, 15013 Denver West Parkway, Golden, Colorado 80401, United States; Ramirez, Kelsey J. [National Bioenergy Center, National Renewable Energy Laboratory, 15013 Denver West Parkway, Golden, Colorado 80401, United States; Nagle, Nicholas J. [National Bioenergy Center, National Renewable Energy Laboratory, 15013 Denver West Parkway, Golden, Colorado 80401, United States; Lowell, Andrew C. [National Bioenergy Center, National Renewable Energy Laboratory, 15013 Denver West Parkway, Golden, Colorado 80401, United States; Beckham, Gregg T. [National Bioenergy Center, National Renewable Energy Laboratory, 15013 Denver West Parkway, Golden, Colorado 80401, United States; McMillan, James D. [National Bioenergy Center, National Renewable Energy Laboratory, 15013 Denver West Parkway, Golden, Colorado 80401, United States; Biddy, Mary J. [National Bioenergy Center, National Renewable Energy Laboratory, 15013 Denver West Parkway, Golden, Colorado 80401, United States

    2018-01-24

    Bio-derived lipids offer a potentially promising intermediate to displace petroleum-derived diesel. One of the key challenges for the production of lipids via microbial cell mass is that these products are stored intracellularly and must be extracted and recovered efficiently and economically. Thus, improved methods of cell lysis and lipid extraction are needed. In this study, we examine lipid extraction from wet oleaginous yeast in combination with seven different cell lysis approaches encompassing both physical and chemical techniques (high-pressure homogenization, microwave and conventional thermal treatments, bead beating, acid, base, and enzymatic treatments) to facilitate lipid extraction from a model oleaginous yeast strain, Lipomyces starkeyi. Of the seven techniques investigated, acid treatment led to the highest lipid recovery yields. Further exploration of acid treatment and integration with an economic model revealed that treatment at 170 degrees C for 60 min at 1 wt% H2SO4 and 8 wt% yeast solids represents a viable option for both lipid recovery yield and process economics, enabling experimental lipid recovery yields of 88.5-93.0% to be achieved at a corresponding estimated minimum fuel selling price (MFSP) of $5.13-$5.61/gallon of gasoline equivalent (GGE). The same acid treatment conditions applied to two other strains of oleaginous yeast (Cutaneotrichosporon curvatus and Rhodotorula toruloides) resulted in similar lipid recovery yields. In pretreatment experiments scaled up to 300 mL, slightly lower temperatures or shorter pretreatment times, along with higher yeast solids loading, resulted in higher lipid yields than the conditions identified from the small-scale runs. Two replicate runs carried out at 170 degrees C for 30 min using 1 wt% H2SO4 and 19 wt% yeast solids achieved an average lipid recovery of 96.1% at a corresponding estimated MFSP of $4.89/GGE. In all cases, the lipids are primarily triglycerides and free fatty acids comprised mainly

  17. Intracellular role of exchangeable apolipoproteins in energy homeostasis, obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Wu, Chen-Lu; Zhao, Shui-Ping; Yu, Bi-Lian

    2015-05-01

    Exchangeable apolipoproteins play an important role in systemic lipid metabolism, especially for lipoproteins with which they are associated. Recently, emerging evidence has suggested that exchangeable apolipoproteins, such as apolipoprotein A4 (apoA4), apolipoprotein A5 (apoA5), apolipoprotein C3 (apoC3) and apolipoprotein E (apoE), also exert important effects on intracellular lipid homeostasis. There is a close link between lipid metabolism in adipose tissue and liver because the latter behaves as the metabolic sensor of dysfunctional adipose tissue and is a main target of lipotoxicity. Given that the energy balance between these two major lipogenic organs is intimately involved in the pathogenesis of obesity and non-alcoholic fatty liver disease (NAFLD), we here review recent findings concerning the intracellular function of exchangeable apolipoproteins in triglyceride metabolism in adipocytes and hepatocytes. These apolipoproteins may act as mediators of crosstalk between adipose tissue and liver, thus influencing development of obesity and hepatosteatosis. This review provides new insights into the physiological role of exchangeable apolipoproteins and identifies latent targets for therapeutic intervention of obesity and its related disorders. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

  18. 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 com......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...... 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...

  19. LDL Receptors as Gateways for Intracellular Porphyrin Uptake

    International Nuclear Information System (INIS)

    Novick, S.; Laster, B.; Quastel, M.

    2004-01-01

    Boronated compounds are currently being studied for possible use in Boron Neutron Capture Therapy (BNCT). We found that one of these agents, BOPP (tetrakis-carborane-carboxylate, esters of 2,4-bis (a,b- dihydroxyethyl) deuteroporphyrin IX), could also be labeled with indium (In-BOPP) and, therefore, could also be used potentially to transport high Z atoms into tumor cell DNA for AET (Auger Electron Therapy). In order to assess the uptake of these agents into cells, the role of the LDL receptor in the intracellular accumulation of BOPP and In-BOPP was investigated. Pre-incubation of V-79 Chinese hamster cells in medium containing delipidized fetal bovine serum (FBS) markedly increased the subsequent uptake of intracellular boron transported by both BOPP and In-BOPP when compared with cells that had been pre-incubated with medium containing 10% normal FBS (lipidized). The increased uptake was characterized by elevated levels of receptor, and greater affinity was shown for both BOPP and In-BOPP, although less marked with the latter. Positive cooperativity was demonstrated by sigmoid saturation curves, Scatchard analysis and Hill plots. Increasing the amount of LDL in the incubation medium had a relatively small effect on the total accumulation of either indium or boron atoms inside the cell. Furthermore, chemical acetylation of LDL did not decrease the intracellular uptake of either boron or indium transported by BOPP or In-BOPP. It is thus concluded that BOPP and In-BOPP preferentially enter the cells directly by way of the LDL receptor and that only a small fraction of these molecules are transported into the cells indirectly using serum LDLs as their carriers. These data suggest a novel way of bringing greater amounts of boron and indium (and perhaps other agents) into tissues. Porphyrins can be used to transport different agents into tumor cells because they are tumor affinic molecules. Tumors express a higher number of LDL receptors than do most normal tissues

  20. Gravimetric enrichment of high lipid and starch accumulating microalgae.

    Science.gov (United States)

    Hassanpour, Morteza; Abbasabadi, Mahsa; Ebrahimi, Sirous; Hosseini, Maryam; Sheikhbaglou, Ahmad

    2015-11-01

    This study presents gravimetric enrichment of mixed culture to screen starch and lipid producing species separately in a sequencing batch reactor. In the enriched starch-producing mixed culture photobioreactor, the starch content at the end of steady state batch became 3.42 times the beginning of depletion. Whereas in the enriched lipid-producing photobioreactor, the lipid content at the end of steady state batch became 3 times the beginning of famine phase. The obtained results revealed that the gravimetric enrichment is a suitable screening method for specific production of storage compounds in none-sterile large-scaled condition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Hepatitis C virus intracellular host interactions

    NARCIS (Netherlands)

    Liefhebber, Johanna Maaike Pieternella

    2010-01-01

    Hepatitis C virus (HCV) infects about 170 million people worldwide causing a major healthcare problem. The virus lifecycle is greatly dependent on the host-cell for effective replication. In this thesis, the intracellular interactions of the non-structural HCV proteins with the host-cell were

  2. Enhanced production of intracellular dextran dextrinase from ...

    African Journals Online (AJOL)

    Enhanced production of intracellular dextran dextrinase from Gluconobacter oxydans using statistical experimental methods. ... the Plackett-Burman screening. A four-factor five-level central composite design (CCD) was chosen to explain the combined effects of the four medium constituents. The optimum medium consisted ...

  3. Biological synthesis and characterization of intracellular gold ...

    Indian Academy of Sciences (India)

    ... nontoxic, safe, biocompatible and environmentally acceptable. In the present study, Aspergillus fumigatus was used for the intracellular synthesis of gold nanoparticles. Stable nanoparticles were produced when an aqueous solution of chloroauric acid (HAuCl4) was reduced by A. fumigatus biomass as the reducing agent ...

  4. Efficient intracellular delivery of native proteins

    NARCIS (Netherlands)

    D'Astolfo, Diego S; Pagliero, Romina J; Pras, Anita; Karthaus, Wouter R; Clevers, Hans; Prasad, Vikram; Lebbink, Robert Jan; Rehmann, Holger; Geijsen, Niels

    2015-01-01

    Modulation of protein function is used to intervene in cellular processes but is often done indirectly by means of introducing DNA or mRNA encoding the effector protein. Thus far, direct intracellular delivery of proteins has remained challenging. We developed a method termed iTOP, for induced

  5. Temporal protein expression pattern in intracellular signalling ...

    Indian Academy of Sciences (India)

    2015-09-28

    Sep 28, 2015 ... [Ganguli P, Chowdhury S, Bhowmick R and Sarkar RR 2015 Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: A ... cells and tissues by studying different signalling pathways, such as Hedgehog ...... Murray JD 2003 On the mechanochemical theory of biological.

  6. Influence of frozen storage on the fatty acid composition of ostrich ...

    African Journals Online (AJOL)

    2015-05-16

    May 16, 2015 ... frozen storage (−20 ºC) on the fatty acid composition of meat from ostriches supplemented with linseed and rapeseed. ... Thus, the benefit of this composition requires storage conditions that ensure limited lipid oxidation during storage ... Thus, the aim of this study was to determine the changes in fatty acid ...

  7. Intracellular vesicles as reproduction elements in cell wall-deficient L-form bacteria.

    Directory of Open Access Journals (Sweden)

    Yves Briers

    Full Text Available Cell wall-deficient bacteria, or L-forms, represent an extreme example of bacterial plasticity. Stable L-forms can multiply and propagate indefinitely in the absence of a cell wall. Data presented here are consistent with the model that intracellular vesicles in Listeria monocytogenes L-form cells represent the actual viable reproductive elements. First, small intracellular vesicles are formed along the mother cell cytoplasmic membrane, originating from local phospholipid accumulation. During growth, daughter vesicles incorporate a small volume of the cellular cytoplasm, and accumulate within volume-expanding mother cells. Confocal Raman microspectroscopy demonstrated the presence of nucleic acids and proteins in all intracellular vesicles, but only a fraction of which reveals metabolic activity. Following collapse of the mother cell and release of the daughter vesicles, they can establish their own membrane potential required for respiratory and metabolic processes. Premature depolarization of the surrounding membrane promotes activation of daughter cell metabolism prior to release. Based on genome resequencing of L-forms and comparison to the parental strain, we found no evidence for predisposing mutations that might be required for L-form transition. Further investigations revealed that propagation by intracellular budding not only occurs in Listeria species, but also in L-form cells generated from different Enterococcus species. From a more general viewpoint, this type of multiplication mechanism seems reminiscent of the physicochemical self-reproducing properties of abiotic lipid vesicles used to study the primordial reproduction pathways of putative prokaryotic precursor cells.

  8. Optimizing Nanoelectrode Arrays for Scalable Intracellular Electrophysiology.

    Science.gov (United States)

    Abbott, Jeffrey; Ye, Tianyang; Ham, Donhee; Park, Hongkun

    2018-03-20

    Electrode technology for electrophysiology has a long history of innovation, with some decisive steps including the development of the voltage-clamp measurement technique by Hodgkin and Huxley in the 1940s and the invention of the patch clamp electrode by Neher and Sakmann in the 1970s. The high-precision intracellular recording enabled by the patch clamp electrode has since been a gold standard in studying the fundamental cellular processes underlying the electrical activities of neurons and other excitable cells. One logical next step would then be to parallelize these intracellular electrodes, since simultaneous intracellular recording from a large number of cells will benefit the study of complex neuronal networks and will increase the throughput of electrophysiological screening from basic neurobiology laboratories to the pharmaceutical industry. Patch clamp electrodes, however, are not built for parallelization; as for now, only ∼10 patch measurements in parallel are possible. It has long been envisioned that nanoscale electrodes may help meet this challenge. First, nanoscale electrodes were shown to enable intracellular access. Second, because their size scale is within the normal reach of the standard top-down fabrication, the nanoelectrodes can be scaled into a large array for parallelization. Third, such a nanoelectrode array can be monolithically integrated with complementary metal-oxide semiconductor (CMOS) electronics to facilitate the large array operation and the recording of the signals from a massive number of cells. These are some of the central ideas that have motivated the research activity into nanoelectrode electrophysiology, and these past years have seen fruitful developments. This Account aims to synthesize these findings so as to provide a useful reference. Summing up from the recent studies, we will first elucidate the morphology and associated electrical properties of the interface between a nanoelectrode and a cellular membrane

  9. Fuel storage

    International Nuclear Information System (INIS)

    Palacios, C.; Alvarez-Miranda, A.

    2009-01-01

    ENSA is a well known manufacturer of multi-system primary components for the nuclear industry and is totally prepared to satisfy future market requirements in this industry. At the same time that ENSA has been gaining a reputation world wider for the supply of primary components, has been strengthening its commitment and experience in supplying spent fuel components, either pool racks or storage and transportation casks, and offers not only fabrication but also design capabilities for its products. ENSA has supplied Spent Fuel Pool Racks, in spain, Finland, Taiwan, Korea, China, and currently it is in the process of licensing its own rack design in the United States of America for the ESBWR along with Ge-Hitachi. ENSA has supplied racks for 20 pools and 22 different reactors and it has also manufactured racks under all available technologies and developed a design known as Interlock Cell Matrix whose main features are outlined in this article. Another ENSA achievement in rack technology is the use of remote control for re-racking activities instead of using divers, which improves the ALARA requirements. Regarding casks for storage and transportation, ENSA also has al leading worldwide position, with exports prevailing over the Spanish market where ENSA has supplied 16 storage and transportation casks to the Spanish nuclear power Trillo. In some cases, ENSA acts as subcontractor for other clients. Foreign markets are still a major challenge for ENSA. ENSA-is well known for its manufacturing capabilities in the nuclear industry, but has been always involved in design activities through its engineering division, which carries out different tasks: components Design; Tooling Design; Engineering and Documentation; Project Engineering; Calculations, Design and Development Engineering. (Author)

  10. Therapeutic Antibodies against Intracellular Tumor Antigens

    Directory of Open Access Journals (Sweden)

    Iva Trenevska

    2017-08-01

    Full Text Available Monoclonal antibodies are among the most clinically effective drugs used to treat cancer. However, their target repertoire is limited as there are relatively few tumor-specific or tumor-associated cell surface or soluble antigens. Intracellular molecules represent nearly half of the human proteome and provide an untapped reservoir of potential therapeutic targets. Antibodies have been developed to target externalized antigens, have also been engineered to enter into cells or may be expressed intracellularly with the aim of binding intracellular antigens. Furthermore, intracellular proteins can be degraded by the proteasome into short, commonly 8–10 amino acid long, peptides that are presented on the cell surface in the context of major histocompatibility complex class I (MHC-I molecules. These tumor-associated peptide–MHC-I complexes can then be targeted by antibodies known as T-cell receptor mimic (TCRm or T-cell receptor (TCR-like antibodies, which recognize epitopes comprising both the peptide and the MHC-I molecule, similar to the recognition of such complexes by the TCR on T cells. Advances in the production of TCRm antibodies have enabled the generation of multiple TCRm antibodies, which have been tested in vitro and in vivo, expanding our understanding of their mechanisms of action and the importance of target epitope selection and expression. This review will summarize multiple approaches to targeting intracellular antigens with therapeutic antibodies, in particular describing the production and characterization of TCRm antibodies, the factors influencing their target identification, their advantages and disadvantages in the context of TCR therapies, and the potential to advance TCRm-based therapies into the clinic.

  11. Storage pond

    International Nuclear Information System (INIS)

    Hunter, E.; Watson, E.

    1983-01-01

    A pond is described for the storage of hazardous materials, such as irradiated nuclear fuel elements, under water. Upper and lower impervious membranes extend without interruption beneath the floor of the pond and the edges of the membranes lead into a trench surrounding the pond. Any leakage through the floor is directed normally by the upper membrane into the trench. The lower membrane provides an additional impervious barrier in the event of a leak in the upper membrane and again directs the leakage into the trench thereby avoiding contamination of the ground beneath the pond. (author)

  12. Energy Storage

    CSIR Research Space (South Africa)

    Bladergroen, B

    2015-10-01

    Full Text Available will be an important tool in the toolbox of system designers – together with primary energy providers solar PV, wind, biogas and potentially backup through diesel-based generators. Outside the electricity sector, eMobility will largely drive the demand for battery...-to-Fuel is, together with eMobility, the connector between the historically separated electricity and transport sector. Challenge Questions  What will drive the future battery market?  Is energy storage a necessary condition for a large uptake...

  13. A REVIEW ON CORRELATION BETWEEN LIPID PROFILE AND DEPRESSION

    Directory of Open Access Journals (Sweden)

    Lalitha Devi Dhulipala

    2016-07-01

    Full Text Available Epidemiological and clinical intervention data indicate that low levels of circulating lipids and cholesterol are the risk factors for depressive symptoms. Olie et al 2011 (1 showed an association of low cholesterol and self-harm in their study. In the present scenario, depression and anxiety disorders have high prevalence rates and are frequently related. Understanding the subject and concepts/mechanisms related to neurobiological basis for these disorders is very important and the available techniques or methods are ineffective. Lipids generally play an important role in neural function in the brain. The composition of lipid of the brain influences perception, mood and behaviour. Lipids are responsible to regulate the membrane's function which acts as a barrier between the intracellular and extracellular spaces. It is found that membrane lipids determine the local behaviour and characterisation and function of proteins within the membrane. It is found from the literature that lipids can influence both exo-and endocytic processes and work within the membrane as second messengers. This paper discusses some important case studies related to the correlation between lipid profile and the depression.

  14. Phenotypic screening with oleaginous microalgae reveals modulators of lipid productivity.

    Science.gov (United States)

    Franz, Annaliese K; Danielewicz, Megan A; Wong, Diana M; Anderson, Lisa A; Boothe, Jordan R

    2013-05-17

    Here we describe the first phenotypic screening with microalgae to study lipid metabolism and to discover organic small molecules as chemical triggers that increase growth and lipid production. A microplate assay has been developed for analysis of intracellular lipids using Nile Red fluorescence in order to screen a collection of diverse bioactive organic molecules (e.g., kinase inhibitors) with four strains of oleaginous microalgae (Nannochloropsis salina, Nannochloropsis oculata, Nannochloris sp., and Phaeodactylum tricornutum). Several small molecules identified in microplate screening increased lipid productivity >200% without decreasing growth and biomass production. Selected compounds were further investigated in the context of larger batch culture experiments (e.g., 500 mL) and demonstrated to increase lipid levels (up to 84%) while maintaining or increasing the specific growth rate. Bioactive molecules such as forskolin and quinacrine were identified as promising probes of microalgae lipid pathways. We have also determined that common antioxidants such as epigallocatechin gallate and butylated hydroxyanisole (BHA) increase lipid productivity and may represent new probes of oxidative signaling pathways for photooxidative protection.

  15. Light-induced dynamic structural color by intracellular 3D photonic crystals in brown algae.

    Science.gov (United States)

    Lopez-Garcia, Martin; Masters, Nathan; O'Brien, Heath E; Lennon, Joseph; Atkinson, George; Cryan, Martin J; Oulton, Ruth; Whitney, Heather M

    2018-04-01

    Natural photonic crystals are responsible for strong reflectance at selective wavelengths in different natural systems. We demonstrate that intracellular opal-like photonic crystals formed from lipids within photosynthetic cells produce vivid structural color in the alga Cystoseira tamariscifolia . The reflectance of the opaline vesicles is dynamically responsive to environmental illumination. The structural color is present in low light-adapted samples, whereas higher light levels produce a slow disappearance of the structural color such that it eventually vanishes completely. Once returned to low-light conditions, the color re-emerges. Our results suggest that these complex intracellular natural photonic crystals are responsive to environmental conditions, changing their packing structure reversibly, and have the potential to manipulate light for roles beyond visual signaling.

  16. Relation between dietary lipid level and voluntary feed intake, growth, nutrient gain, lipid deposition and hepatic lipogenesis in rainbow trout.

    Science.gov (United States)

    Gélineau, A; Corraze, G; Boujard, T; Larroquet, L; Kaushik, S

    2001-01-01

    Four diets with differing lipid contents (15, 20, 25 or 30% DM) were tested on small (initial body weight: 27 g) and larger (IBW: 93 g) rainbow trout (Oncorhynchus mykiss) fed on demand or by hand, respectively. In both trials, voluntary feed intake was inversely related to dietary lipid levels. Protein efficiency increased when dietary fat content increased. Final whole-body lipid content was positively related to dietary lipid levels. The main sites of lipid storage were visceral adipose tissue and to a lesser extent muscle. Increased fat deposition in the visceral cavity of young trout was due to both hyperplasic and hypertrophic responses and in larger trout mostly due to a hypertrophic response. Liver activities of glucose-6-phosphate dehydrogenase and fatty acid synthetase were negatively correlated with fat intake and positively with starch intake, whereas malic enzyme was little affected by dietary treatments.

  17. Effects of silicon deficiency on lipid and carbohydrate metabolism in the diatom Cyclotella cryptica

    International Nuclear Information System (INIS)

    Roessler, P.G.

    1987-01-01

    Previous studies have shown that silicon deficiency induces lipid accumulation in certain diatom species. The nature of the lipids produced under these conditions was not investigated, however, and the biochemical mechanisms which underlie this phenomenon were not determined. Research was carried out in order to increase our knowledge concerning the aspects of lipid accumulation in diatoms. The first phase of this project indicated that the diatoms C. cryptica, Cylindrotheca fusiformis, and Thalassiosira pseudonana accumulated storage lipids when grown under silicon-limiting conditions. The ratio of saturated and monounsaturated fatty acids to polyunsaturated fatty acids in C. cryptica cells increased markedly after 24 hours of silicon deficiency. Tracer experiments with [ 14 C]bicarbonate suggested that lipid accumulation in silicon-limited C. cryptica cells was due to two distinct processes: (1) an increase in the amount of newly photoassimilated carbon partitioned into lipids, and (2) a slow conversion of non-lipid compounds (carbohydrates and presumably proteins) into lipids

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    Microscopy of lipids in living cells is currently hampered by a lack of adequate fluorescent tags. The most frequently used tags, NBD and BODIPY, strongly influence the properties of lipids, yielding analogs with quite different characteristics. Here, we introduce polyene-lipids containing five...... 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. The evolution of lipids

    Science.gov (United States)

    Itoh, Y. H.; Sugai, A.; Uda, I.; Itoh, T.

    2001-01-01

    Living organisms on the Earth which are divided into three major domains - Archaea, Bacteria, and Eucarya, probably came from a common ancestral cell. Because there are many thermophilic microorganisms near the root of the universal phylogenetic tree, the common ancestral cell should be considered to be a thermophilic microorganism. The existence of a cell is necessary for the living organisms; the cell membrane is the essential structural component of a cell, so its amphiphilic property is vital for the molecule of lipids for cell membranes. Tetraether type glycerophospholipids with C 40 isoprenoid chains are major membrane lipids widely distributed in archaeal cells. Cyclization number of C 40 isoprenoid chains in thermophilic archaea influences the fluidity of lipids whereas the number of carbons and degree of unsaturation in fatty acids do so in bacteria and eucarya. In addition to the cyclization of the tetraether lipids, covalent bonding of two C 40 isoprenoid chains was found in hyperthermophiles. These characteristic structures of the lipids seem to contribute to their fundamental physiological roles in hyperthermophiles. Stereochemical differences between G-1-P archaeal lipids and G-3-P bacterial and eucaryal lipids might have occured by the function of some proteins long after the first cell was developed by the reactions of small organic molecules. We propose that the structure of lipids of the common ancestral cell may have been similar to those of hyperthermophilic archaea.

  20. Crystal structures of the TRIC trimeric intracellular cation channel orthologues.

    Science.gov (United States)

    Kasuya, Go; Hiraizumi, Masahiro; Maturana, Andrés D; Kumazaki, Kaoru; Fujiwara, Yuichiro; Liu, Keihong; Nakada-Nakura, Yoshiko; Iwata, So; Tsukada, Keisuke; Komori, Tomotaka; Uemura, Sotaro; Goto, Yuhei; Nakane, Takanori; Takemoto, Mizuki; Kato, Hideaki E; Yamashita, Keitaro; Wada, Miki; Ito, Koichi; Ishitani, Ryuichiro; Hattori, Motoyuki; Nureki, Osamu

    2016-12-01

    Ca 2+ release from the sarcoplasmic reticulum (SR) and endoplasmic reticulum (ER) is crucial for muscle contraction, cell growth, apoptosis, learning and memory. The trimeric intracellular cation (TRIC) channels were recently identified as cation channels balancing the SR and ER membrane potentials, and are implicated in Ca 2+ signaling and homeostasis. Here we present the crystal structures of prokaryotic TRIC channels in the closed state and structure-based functional analyses of prokaryotic and eukaryotic TRIC channels. Each trimer subunit consists of seven transmembrane (TM) helices with two inverted repeated regions. The electrophysiological, biochemical and biophysical analyses revealed that TRIC channels possess an ion-conducting pore within each subunit, and that the trimer formation contributes to the stability of the protein. The symmetrically related TM2 and TM5 helices are kinked at the conserved glycine clusters, and these kinks are important for the channel activity. Furthermore, the kinks of the TM2 and TM5 helices generate lateral fenestrations at each subunit interface. Unexpectedly, these lateral fenestrations are occupied with lipid molecules. This study provides the structural and functional framework for the molecular mechanism of this ion channel superfamily.

  1. A simple guide to biochemical approaches for analyzing protein–lipid interactions

    Science.gov (United States)

    Zhao, Hongxia; Lappalainen, Pekka

    2012-01-01

    Eukaryotic cells contain many different membrane compartments with characteristic shapes, lipid compositions, and dynamics. A large fraction of cytoplasmic proteins associate with these membrane compartments. Such protein–lipid interactions, which regulate the subcellular localizations and activities of peripheral membrane proteins, are fundamentally important for a variety of cell biological processes ranging from cytoskeletal dynamics and membrane trafficking to intracellular signaling. Reciprocally, many membrane-associated proteins can modulate the shape, lipid composition, and dynamics of cellular membranes. Determining the exact mechanisms by which these proteins interact with membranes will be essential to understanding their biological functions. In this Technical Perspective, we provide a brief introduction to selected biochemical methods that can be applied to study protein–lipid interactions. We also discuss how important it is to choose proper lipid composition, type of model membrane, and biochemical assay to obtain reliable and informative data from the lipid-interaction mechanism of a protein of interest. PMID:22848065

  2. A simple guide to biochemical approaches for analyzing protein-lipid interactions.

    Science.gov (United States)

    Zhao, Hongxia; Lappalainen, Pekka

    2012-08-01

    Eukaryotic cells contain many different membrane compartments with characteristic shapes, lipid compositions, and dynamics. A large fraction of cytoplasmic proteins associate with these membrane compartments. Such protein-lipid interactions, which regulate the subcellular localizations and activities of peripheral membrane proteins, are fundamentally important for a variety of cell biological processes ranging from cytoskeletal dynamics and membrane trafficking to intracellular signaling. Reciprocally, many membrane-associated proteins can modulate the shape, lipid composition, and dynamics of cellular membranes. Determining the exact mechanisms by which these proteins interact with membranes will be essential to understanding their biological functions. In this Technical Perspective, we provide a brief introduction to selected biochemical methods that can be applied to study protein-lipid interactions. We also discuss how important it is to choose proper lipid composition, type of model membrane, and biochemical assay to obtain reliable and informative data from the lipid-interaction mechanism of a protein of interest.

  3. Monosodium glutamate inhibits the lymphatic transport of lipids in the rat.

    Science.gov (United States)

    Kohan, Alison B; Yang, Qing; Xu, Min; Lee, Dana; Tso, Patrick

    2016-10-01

    It is not well understood how monosodium glutamate (MSG) affects gastrointestinal physiology, especially regarding the absorption and the subsequent transport of dietary lipids into lymph. Thus far, there is little information about how the ingestion of MSG affects the lipid lipolysis, uptake, intracellular esterification, and formation and secretion of chylomicrons. Using lymph fistula rats treated with the infusion of a 2% MSG solution before a continuous infusion of triglyceride, we show that MSG causes a significant decrease in both triglyceride and cholesterol secretion into lymph. Intriguingly, the diminished lymphatic transport of triglyceride and cholesterol was not caused by an accumulation of these labeled lipids in the intestinal lumen or in the intestinal mucosa. Rather, it is a result of increased portal transport in the animals fed acutely the lipid plus 2% MSG in the lipid emulsion. This is a first demonstration of MSG on intestinal lymphatic transport of lipids. Copyright © 2016 the American Physiological Society.

  4. Fast intracellular dissolution and persistent cellular uptake of silver nanoparticles in CHO-K1 cells: implication for cytotoxicity

    DEFF Research Database (Denmark)

    Jiang, Xiumei; Miclaus, Teodora; Wang, Liming

    2015-01-01

    Toxicity of silver nanoparticles (Ag NPs) has been reported both in vitro and in vivo. However, the intracellular stability and chemical state of Ag NPs are still not very well studied. In this work, we systematically investigated the cellular uptake pathways, intracellular dissolution and chemic...... is related to the intracellular release of silver ions, followed by their binding to SH-groups, presumably coming from amino acids or proteins, and affecting protein functions and the antioxidant defense system of cells....... lipid-raft-mediated endocytosis and energy-independent diffusion. The degradation study shows that Ag NPs taken up into cells dissolved quickly and XANES results directly indicated that the internalized Ag was oxidized to Ag−O− species and then stabilized in silver−sulfur (Ag−S−) bonds within the cells...

  5. Lipid oxidation promotes acrylamide formation in fat-rich model systems

    NARCIS (Netherlands)

    Capuano, E.; Oliviero, T.; Açar, Ö.; Gökmen, V.; Fogliano, V.

    2010-01-01

    Lipid oxidation is one of the major chemical reactions occurring during food processing or storage and may have a strong impact on the final quality of foods. A significant role of carbonyl compounds derived from lipid oxidation in acrylamide formation has been recently proposed. In this work, the

  6. Lipid recovery from a vegetable oil emulsion using microbial enrichment cultures

    NARCIS (Netherlands)

    Tamis, J.; Sorokin, D.Y.; Jiang, Y.; Van Loosdrecht, M.C.M.; Kleerebezem, R.

    2015-01-01

    Background Many waste streams have a relatively high vegetable oil content, which is a potential resource that should be recovered. Microbial storage compound production for the recovery of lipids from lipid-water emulsions with open (unsterilized) microbial cultures was investigated in a sequencing

  7. Oxidative stability of milk drinks containing structured lipids produced from sunflower oil and caprylic acid

    DEFF Research Database (Denmark)

    Timm Heinrich, Maike; Xu, Xuebing; Nielsen, Nina Skall

    2003-01-01

    Milk drinks containing 5% traditional sunflower oil (SO), randomized lipid (RL) or specific structured lipid (SL) (both produced from SO and tricaprylin/caprylic acid) were compared with respect to their particle size, viscosity and oxidative stability during storage. Furthermore, the effect...

  8. Red Blood Cell Storage Lesion

    Directory of Open Access Journals (Sweden)

    Daryl J. Kor

    2009-10-01

    Full Text Available The past two decades have witnessed increased scrutiny regarding efficacy and risk of the once unquestioned therapy of red blood cell (RBC transfusion. Simultaneously, a variety of changes have been identified within the RBC and storage media during RBC preservation that are correlated with reduced tissue oxygenation and transfusion-associated adverse effects. These alterations are collectively termed the storage lesion and include extensive biochemical, biomechanical, and immunologic changes involving cells of diverse origin. Time-dependent falls is 2,3-diphosphoglycerate, intracellular RBC adenosine triphosphate, and nitric oxide have been shown to impact RBC deformability and delivery of oxygen to the end-organ. The accumulation of biologic response modifiers such as soluble CD40 ligand (sCD40L, lysophosphatidylcholine (lyso-PC, and Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES have been associated with altered recipient immune function as well. This review will address the alterations occurring within the RBC and storage media during RBC preservation and will address the potential clinical consequence thereof.

  9. Reduction of intracellular glutathione content and radiosensitivity

    International Nuclear Information System (INIS)

    Vos, O.; Schans, G.P. van der; Roos-Verheij, W.S.D.

    1986-01-01

    The intracellular glutathione (GSH) content of HeLa, CHO and V79 cells was reduced by incubating the cells in growth medium containing buthionine sulphoximine or diethyl maleate (DEM). Clonogenicity, single-strand DNA breaks (ssb) and double-strand DNA breaks (dsb) were used as criteria for radiation-induced damage after X- or γ-irradiation. In survival experiments, DEM gave a slightly larger sensitization although it gave a smaller reduction of the intracellular GSH. In general, sensitization was larger for dsb than for ssb, also the reduction of the o.e.r. was generally larger for dsb than for ssb. This may be due to the higher dose rate in case of dsb experiments resulting in a higher rate of radiochemical oxygen consumption. In general, no effect was found on post-irradiation repair of ssb and dsb. (author)

  10. Intracellular mechanisms of solar water disinfection

    Science.gov (United States)

    Castro-Alférez, María; Polo-López, María Inmaculada; Fernández-Ibáñez, Pilar

    2016-12-01

    Solar water disinfection (SODIS) is a zero-cost intervention measure to disinfect drinking water in areas of poor access to improved water sources, used by more than 6 million people in the world. The bactericidal action of solar radiation in water has been widely proven, nevertheless the causes for this remain still unclear. Scientific literature points out that generation of reactive oxygen species (ROS) inside microorganisms promoted by solar light absorption is the main reason. For the first time, this work reports on the experimental measurement of accumulated intracellular ROS in E. coli during solar irradiation. For this experimental achievement, a modified protocol based on the fluorescent probe dichlorodihydrofluorescein diacetate (DCFH-DA), widely used for oxidative stress in eukaryotic cells, has been tested and validated for E. coli. Our results demonstrate that ROS and their accumulated oxidative damages at intracellular level are key in solar water disinfection.

  11. Reduction of intracellular glutathione content and radiosensitivity

    International Nuclear Information System (INIS)

    Vos, O.; Schans, G.P. van der; Roos-Verheij, W.S.D.

    1986-05-01

    The intracellular glutathione (GSH) content in HeLa, CHO and V79 cells was reduced by incubating the cells in growth medium containing buthionine sulfoximine (BSO) or diethyl maleate (DEM). Clonogenicity, single strand DNA breaks (ssb) and double strand DNA breaks (dsb) were used as criteria for radiation induced damage after X- or γ irradiation. In survival experiments DEM gave a slightly larger sensitization although it gave a smaller reduction of the intracellular GSH. In general, sensitization was larger for dsb than for ssb, also the reduction of the OER was generally larger for dsb than for ssb. This may be due to the higher dose rate in case of dsb experiments resulting in a higher rate of radiochemical oxygen consumption. In general, no effect was found on post-irradiation repair of ssb and dsb. (Auth.)

  12. Glycogen storage in tissue-engineered cartilage.

    Science.gov (United States)

    Suits, Jocelyne M T; Khan, Aasma A; Waldman, Stephen D

    2008-08-01

    Recent focus in cartilage tissue engineering has been to develop functional tissue that can survive after implantation. One such determinant is the ability of the engineered tissue to be able to sustain its metabolic activity post-implantation. In vivo, chondrocytes contain stores of intracellular glycogen to support metabolism and it is unknown whether these cells can store glycogen during tissue growth in vitro. Thus, the purpose of this study was to determine the appropriate nutrient conditions to elicit glycogen storage in tissue-engineered cartilage. Isolated bovine articular chondrocytes were seeded in scaffold-free, 3D culture and grown under different nutrient conditions (glucose concentrations and media volumes) for 4 weeks. Intracellular glycogen storage, glucose utilization and extracellular matrix (ECM) accumulation of the engineered tissues were then evaluated. Glucose concentration (5-10 mM) and media volume (1-4 ml) had no apparent effect on cartilaginous tissue formation. However, glucose consumption by the cells increased in proportion to the volume of medium provided. Lactate production was similarly affected but in direct proportion to the glucose consumed, indicating a change in glucose utilization. Similarly, under elevated medium volume, engineered tissues stained positive for intracellular glycogen, which was also confirmed biochemically (1 ml, 1 +/- 2; 2 ml, 13 +/- 4; 4 ml, 13 +/- 3 microg/construct). The storage of intracellular glycogen in engineered cartilage can be elicited by culturing the constructs in elevated volumes of medium (>or=1 ml medium/million cells), which might help to ensure appropriate metabolic function after implantation. (c) 2008 John Wiley & Sons, Ltd.

  13. Glucocorticoid Antagonism Reduces Insulin Resistance and Associated Lipid Abnormalities in High-Fructose-Fed Mice.

    Science.gov (United States)

    Priyadarshini, Emayavaramban; Anuradha, Carani Venkatraman

    2017-02-01

    High intake of dietary fructose causes perturbation in lipid metabolism and provokes lipid-induced insulin resistance. A rise in glucocorticoids (GCs) has recently been suggested to be involved in fructose-induced insulin resistance. The objective of the study was to investigate the effect of GC blockade on lipid abnormalities in insulin-resistant mice. Insulin resistance was induced in mice by administering a high-fructose diet (HFrD) for 60 days. Mifepristone (RU486), a GC antagonist, was administered to HFrD-fed mice for the last 18 days, and the intracellular and extracellular GC levels, the glucocorticoid receptor (GR) activation and the expression of GC-regulated genes involved in lipid metabolism were examined. HFrD elevated the intracellular GC content in both liver and adipose tissue and enhanced the GR nuclear translocation. The plasma GC level remained unchanged. The levels of free fatty acids and triglycerides in plasma were elevated, accompanied by increased plasma insulin and glucose levels and decreased hepatic glycogen content. Treatment with RU486 reduced plasma lipid levels, tissue GC levels and the expression of GC-targeted genes involved in lipid accumulation, and it improved insulin sensitivity. This study demonstrated that HFrD-induced lipid accumulation and insulin resistance are mediated by enhanced GC in liver and adipose tissue and that GC antagonism might reduce fructose-induced lipid abnormalities and insulin resistance. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  14. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ian Smyth

    2008-09-01

    Full Text Available Harlequin Ichthyosis (HI is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.

  15. [Characteristics of lipid metabolism and the cardiovascular system in glycogenosis types I and III].

    Science.gov (United States)

    Polenova, N V; Strokova, T V; Starodubova, A V

    Glycogen storage disease (GSD) is an inherited metabolic disorder characterized by early childhood lipid metabolic disturbances with potentially proatherogenic effects. The review outlines the characteristics of impaired lipid composition and other changes in the cardiovascular system in GSD types I and III. It analyzes the factors enabling and inhibiting the development of atherosclerosis in patients with GSD. The review describes the paradox of vascular resistance to the development of early atherosclerosis despite the proatherogenic composition of lipids in the patients of this group.

  16. Chemical Profiles of Microalgae with Emphasis on Lipids: A Subcontract Report

    Energy Technology Data Exchange (ETDEWEB)

    Tornabene, T. G.; Hubbard, J. S.

    1984-09-01

    Well balanced cultivated cells that are healthy and unstressed produce the optimum cellular yield. All stress studies for lipids production should be conducted with the established cell mass and not be administered during active cultivation. Cells cultivated continually in suboptimum conditions produce lower cellular yields and continuous cultivation in suboptimum media and environmental conditions produce lower than normal lipid levels. Lipid triggers are preceded by a burst of carbohydrate synthesis and storage.

  17. Intracellular Protein Delivery for Treating Breast Cancer

    Science.gov (United States)

    2014-08-01

    Intracellular delivery of such proteins, including human tumor suppressors (such as p53) (Brown et al., 2009) and exogenous tumor-killing proteins...vivo systems. Nature materials 11, 1038-1043. Chorny, M., Hood, E., Levy, R.J., and Muzykantov, V.R. (2010). Endothelial delivery of antioxidant ...for the ntracellular delivery of such proteins, including human umor suppressors [7] and exogenous tumor-killing proteins 8—10]), is attractive as a

  18. Fluorescent nanoparticles for intracellular sensing: A review

    International Nuclear Information System (INIS)

    Ruedas-Rama, Maria J.; Walters, Jamie D.; Orte, Angel; Hall, Elizabeth A.H.

    2012-01-01

    Highlights: ► Analytical applications of fluorescent nanoparticles (NPs) in intracellular sensing. ► Critical review on performance of QDots, metal NPs, silica NPs, and polymer NPs. ► Highlighted potential of fluorescence lifetime imaging microscopy (FLIM). - Abstract: Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy.

  19. Fluorescent nanoparticles for intracellular sensing: A review

    Energy Technology Data Exchange (ETDEWEB)

    Ruedas-Rama, Maria J., E-mail: mjruedas@ugr.esmailto [Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, Campus Cartuja, 18071, Granada (Spain); Walters, Jamie D. [Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, UK CB2 1QT (United Kingdom); Orte, Angel [Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, Campus Cartuja, 18071, Granada (Spain); Hall, Elizabeth A.H., E-mail: lisa.hall@biotech.cam.ac.uk [Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QT (United Kingdom)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer Analytical applications of fluorescent nanoparticles (NPs) in intracellular sensing. Black-Right-Pointing-Pointer Critical review on performance of QDots, metal NPs, silica NPs, and polymer NPs. Black-Right-Pointing-Pointer Highlighted potential of fluorescence lifetime imaging microscopy (FLIM). - Abstract: Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy.

  20. 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. Copyright © 2014. Published by Elsevier B.V.

  1. Weekly Treatment of 2-Hydroxypropyl-β-cyclodextrin Improves Intracellular Cholesterol Levels in LDL Receptor Knockout Mice

    Directory of Open Access Journals (Sweden)

    Sofie M. A. Walenbergh

    2015-09-01

    Full Text Available Recently, the importance of lysosomes in the context of the metabolic syndrome has received increased attention. Increased lysosomal cholesterol storage and cholesterol crystallization inside macrophages have been linked to several metabolic diseases, such as atherosclerosis and non-alcoholic fatty liver disease (NAFLD. Two-hydroxypropyl-β-cyclodextrin (HP-B-CD is able to redirect lysosomal cholesterol to the cytoplasm in Niemann-Pick type C1 disease, a lysosomal storage disorder. We hypothesize that HP-B-CD ameliorates liver cholesterol and intracellular cholesterol levels inside Kupffer cells (KCs. Hyperlipidemic low-density lipoprotein receptor knockout (Ldlr−/− mice were given weekly, subcutaneous injections with HP-B-CD or control PBS. In contrast to control injections, hyperlipidemic mice treated with HP-B-CD demonstrated a shift in intracellular cholesterol distribution towards cytoplasmic cholesteryl ester (CE storage and a decrease in cholesterol crystallization inside KCs. Compared to untreated hyperlipidemic mice, the foamy KC appearance and liver cholesterol remained similar upon HP-B-CD administration, while hepatic campesterol and 7α-hydroxycholesterol levels were back increased. Thus, HP-B-CD could be a useful tool to improve intracellular cholesterol levels in the context of the metabolic syndrome, possibly through modulation of phyto- and oxysterols, and should be tested in the future. Additionally, these data underline the existence of a shared etiology between lysosomal storage diseases and NAFLD.

  2. An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER

    Directory of Open Access Journals (Sweden)

    Daniel F. Markgraf

    2014-01-01

    Full Text Available 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 domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG degradation and synthesis, promoting the rapid relocalization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption.

  3. High Lipid Induction in Microalgae for Biodiesel Production

    Directory of Open Access Journals (Sweden)

    Peer M. Schenk

    2012-05-01

    Full Text Available Oil-accumulating microalgae have the potential to enable large-scale biodiesel production without competing for arable land or biodiverse natural landscapes. High lipid productivity of dominant, fast-growing algae is a major prerequisite for commercial production of microalgal oil-derived biodiesel. However, under optimal growth conditions, large amounts of algal biomass are produced, but with relatively low lipid contents, while species with high lipid contents are typically slow growing. Major advances in this area can be made through the induction of lipid biosynthesis, e.g., by environmental stresses. Lipids, in the form of triacylglycerides typically provide a storage function in the cell that enables microalgae to endure adverse environmental conditions. Essentially algal biomass and triacylglycerides compete for photosynthetic assimilate and a reprogramming of physiological pathways is required to stimulate lipid biosynthesis. There has been a wide range of studies carried out to identify and develop efficient lipid induction techniques in microalgae such as nutrients stress (e.g., nitrogen and/or phosphorus starvation, osmotic stress, radiation, pH, temperature, heavy metals and other chemicals. In addition, several genetic strategies for increased triacylglycerides production and inducibility are currently being developed. In this review, we discuss the potential of lipid induction techniques in microalgae and also their application at commercial scale for the production of biodiesel.

  4. Zigzag lipid tubules.

    Science.gov (United States)

    Zhao, Yue; Fang, Jiyu

    2008-09-04

    We report a method based on poly(dimethylsiloxane) (PDMS) stamp-assisted moving contact line to bend lipid tubules into zigzags on glass substrates. Atomic force microscopy (AFM) reveals that the zigzag lipid tubules buckle at the bent sites. The measurements of buckling heights as a function of bending angles suggest a gradual buckling mode. By imaging the zigzag tubules with AFM under different loading forces, we study the correlation between the loading force and the tubule compression. The reduced stiffness at the buckling sites of zigzag tubules suggests that lipid molecules are reorganized during the gradual buckling.

  5. Oxidative alterations during human platelet storage

    OpenAIRE

    Göker, Bahar; Özsavcı, Derya; Şener, Azize; Aksoy, Halil; Bağışgil, Vedat; Yanıkkaya Demirel, Gülderen; Uras, Fikriye

    2014-01-01

    SUMMARY: During storage of platelet obtained by apheresis several changes occur. The aimof this study was to investigate the effect of storage on activation, apoptosis, protein pattern,lipid peroxidation, and the levels of nitric oxide (NO) and glutathione (GSH) of platelets. In thisstudy, platelets obtained from healty donors (n=7) by apheresis were kept in an agitator fornine days at 20-24°C. The samples were taken on the 1st, 3 rd, 5 th and 9 th days and plateletswere precipitated. Platele...

  6. Use of magnetic nanobeads to study intracellular antigen processing

    Energy Technology Data Exchange (ETDEWEB)

    Perrin-Cocon, Laure A.; Chesne, Serge; Pignot-Paintrand, Isabelle; Marche, Patrice N.; Villiers, Christian L. E-mail: christian.villiers@cea.fr

    2001-07-01

    Magnetic nanobeads were covalently linked to antigens and used as a tool to simultaneously follow their intracellular transport into the cells and specifically purify the intracellular compartments implicated in antigen processing. The protein content of these vesicles was analysed by 2D-electrophoresis. Furthermore, nanobeads allowed intracellular localisation of the antigen in electron and fluorescence microscopy.

  7. Use of magnetic nanobeads to study intracellular antigen processing

    International Nuclear Information System (INIS)

    Perrin-Cocon, Laure A.; Chesne, Serge; Pignot-Paintrand, Isabelle; Marche, Patrice N.; Villiers, Christian L.

    2001-01-01

    Magnetic nanobeads were covalently linked to antigens and used as a tool to simultaneously follow their intracellular transport into the cells and specifically purify the intracellular compartments implicated in antigen processing. The protein content of these vesicles was analysed by 2D-electrophoresis. Furthermore, nanobeads allowed intracellular localisation of the antigen in electron and fluorescence microscopy

  8. Seasonal thermal energy storage

    Energy Technology Data Exchange (ETDEWEB)

    Allen, R.D.; Kannberg, L.D.; Raymond, J.R.

    1984-05-01

    This report describes the following: (1) the US Department of Energy Seasonal Thermal Energy Storage Program, (2) aquifer thermal energy storage technology, (3) alternative STES technology, (4) foreign studies in seasonal thermal energy storage, and (5) economic assessment.

  9. The role of lipids in psoriasis

    Directory of Open Access Journals (Sweden)

    Anna Baran

    2017-12-01

    Full Text Available Psoriasis, affecting 2–4% of the world’s population, is a chronic recurrent inflammatory skin disease. Its multifactorial aetiopathogenesis consists of, for example, abnormal epidermal proliferation, immune disturbances, and genetic, psychosomatic, environmental and hormonal factors. Psoriasis is also considered to be a systemic disorder closely associated with cardiovascular diseases, atherosclerosis, diabetes mellitus, obesity or metabolic syndrome. Lipids have a variety of biological functions. They participate not only in energy storage and expenditure or the formation of cell membranes, but also in inflammatory and metabolic signalling pathways. Disturbances in their homeostasis lead to the development of immunometabolic disorders, including psoriasis. Based on the available literature, this article presents selected molecular and clinical aspects involved in the multidirectional effect of lipids on psoriasis.

  10. Biomarker for Glycogen Storage Diseases

    Science.gov (United States)

    2017-07-03

    Fructose Metabolism, Inborn Errors; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VI; Glycogen Storage Disease Type VII; Glycogen Storage Disease Type VIII

  11. 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.

  12. 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)

  13. Cinnamon extract regulates intestinal lipid metabolism related gene expression in primary enterocytes of rats

    Science.gov (United States)

    Emerging evidence suggests that the small intestine is not a passive organ, but is actively involved in the regulation of lipid absorption, intracellular transport, and metabolism, and is closely linked to systemic lipoprotein metabolism. We have reported previously that the water-soluble components...

  14. Lipids in preventive dentistry.

    Science.gov (United States)

    Kensche, A; Reich, M; Kümmerer, K; Hannig, M; Hannig, C

    2013-04-01

    There is still a great demand for the improvement of oral prophylaxis methods. One repeatedly described approach is rinsing with edible oils. The aim of the present review paper was to analyze the role of lipids in bioadhesion and preventive dentistry. Despite limited sound scientific data, extensive literature search was performed to illustrate possible effects of lipids in the oral cavity. It is to be assumed that lipophilic components modulate the process of bioadhesion to the oral hard tissues as well as the composition and ultrastructure of the initial oral biofilm or the pellicle, respectively. Thereby, lipids could add hydrophobic characteristics to the tooth surface hampering bacterial colonization and eventually decreasing caries susceptibility. Also, a lipid-enriched pellicle might be more resistant in case of acid exposure and could therefore reduce the erosive mineral loss. Furthermore, anti-inflammatory effects on the oral soft tissues were described. However, there is only limited evidence for these beneficial impacts. Neither the lipid composition of saliva and pellicle nor the interactions of lipids with the initial oral biofilm and the pellicle layer have been investigated adequately until now. Edible oils might qualify as mild supplements to conventional strategies for the prevention of caries, erosion, and periodontal diseases but further research is necessary. Against the background of current scientific and empirical knowledge, edible oils might be used as oral hygiene supplements but a decisive benefit for the oral health status is questionable.

  15. 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.

  16. The Making and Taking of Lipids: The Role of Bacterial Lipid Synthesis and the Harnessing of Host Lipids in Bacterial Pathogenesis.

    Science.gov (United States)

    Fozo, E M; Rucks, E A

    2016-01-01

    In order to survive environmental stressors, including those induced by growth in the human host, bacterial pathogens will adjust their membrane physiology accordingly. These physiological changes also include the use of host-derived lipids to alter their own membranes and feed central metabolic pathways. Within the host, the pathogen is exposed to many stressful stimuli. A resulting adaptation is for pathogens to scavenge the host environment for readily available lipid sources. The pathogen takes advantage of these host-derived lipids to increase or decrease the rigidity of their own membranes, to provide themselves with valuable precursors to feed central metabolic pathways, or to impact host signalling and processes. Within, we review the diverse mechanisms that both extracellular and intracellular pathogens employ to alter their own membranes as well as their use of host-derived lipids in membrane synthesis and modification, in order to increase survival and perpetuate disease within the human host. Furthermore, we discuss how pathogen employed mechanistic utilization of host-derived lipids allows for their persistence, survival and potentiation of disease. A more thorough understanding of all of these mechanisms will have direct consequences for the development of new therapeutics, and specifically, therapeutics that target pathogens, while preserving normal flora. © 2016 Elsevier Ltd All rights reserved.

  17. Mapping Condition-Dependent Regulation of Lipid Metabolism in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Jewett, Michael Christopher; Workman, Christopher; Nookaew, Intawat

    2013-01-01

    Lipids play a central role in cellular function as constituents of membranes, as signaling molecules, and as storage materials. Although much is known about the role of lipids in regulating specific steps of metabolism, comprehensive studies integrating genome-wide expression data, metabolite...... levels, and lipid levels are currently lacking. Here, we map condition-dependent regulation controlling lipid metabolism in Saccharomyces cerevisiae by measuring 5636 mRNAs, 50 metabolites, 97 lipids, and 57 13C-reaction fluxes in yeast using a three-factor full-factorial design. Correlation analysis...... across eight environmental conditions revealed 2279 gene expression level-metabolite/lipid relationships that characterize the extent of transcriptional regulation in lipid metabolism relative to major metabolic hubs within the cell. To query this network, we developed integrative methods for correlation...

  18. Changes in dark chocolate volatiles during storage.

    Science.gov (United States)

    Nightingale, Lia M; Cadwallader, Keith R; Engeseth, Nicki J

    2012-05-09

    Chocolate storage is critical to the quality of the final product. Inadequate storage, especially with temperature fluctuations, may lead to a change in crystal structure, which may eventually cause fat bloom. Bloom is the main cause of quality loss in the chocolate industry. The impact of various storage conditions on the flavor quality of dark chocolate was determined. Dark chocolate was stored in different conditions leading to either fat or sugar bloom and analyzed at 0, 4, and 8 weeks of storage. Changes in chocolate flavor were determined by volatile analysis and descriptive sensory evaluation. Results were analyzed by analysis of variance (ANOVA), cluster analysis, principal component analysis (PCA), and linear partial least-squares regression analysis (PLS). Volatile concentration and loss were significantly affected by storage conditions. Chocolates stored at high temperature were the most visually and texturally compromised, but volatile concentrations were affected the least, whereas samples stored at ambient, frozen, and high relative humidity conditions had significant volatile loss during storage. It was determined that high-temperature storage caused a change in crystal state due to the polymorphic shift to form VI, leading to an increase in sample hardness. Decreased solid fat content (SFC) during high-temperature storage increased instrumentally determined volatile retention, although no difference was detected in chocolate flavor during sensory analysis, possibly due to instrumental and sensory sampling techniques. When all instrumental and sensory data had been taken into account, the storage condition that had the least impact on texture, surface roughness, grain size, lipid polymorphism, fat bloom formation, volatile concentrations, and sensory attributes was storage at constant temperature and 75% relative humidity.

  19. Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein.

    Science.gov (United States)

    Chung, Stacey; Ghelfi, Mikel; Atkinson, Jeffrey; Parker, Robert; Qian, Jinghui; Carlin, Cathleen; Manor, Danny

    2016-08-12

    α-Tocopherol (vitamin E) is an essential nutrient for all vertebrates. From the eight naturally occurring members of the vitamin E family, α-tocopherol is the most biologically active species and is selectively retained in tissues. The hepatic α-tocopherol transfer protein (TTP) preferentially selects dietary α-tocopherol and facilitates its transport through the hepatocyte and its secretion to the circulation. In doing so, TTP regulates body-wide levels of α-tocopherol. The mechanisms by which TTP facilitates α-tocopherol trafficking in hepatocytes are poorly understood. We found that the intracellular localization of TTP in hepatocytes is dynamic and responds to the presence of α-tocopherol. In the absence of the vitamin, TTP is localized to perinuclear vesicles that harbor CD71, transferrin, and Rab8, markers of the recycling endosomes. Upon treatment with α-tocopherol, TTP- and α-tocopherol-containing vesicles translocate to the plasma membrane, prior to secretion of the vitamin to the exterior of the cells. The change in TTP localization is specific to α-tocopherol and is time- and dose-dependent. The aberrant intracellular localization patterns of lipid binding-defective TTP mutants highlight the importance of protein-lipid interaction in the transport of α-tocopherol. These findings provide the basis for a proposed mechanistic model that describes TTP-facilitated trafficking of α-tocopherol through hepatocytes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts

    NARCIS (Netherlands)

    Van den Bossche, Lindsay; Schoonenberg, Vivien A C; Burgener, Iwan A; Penning, Louis C; Schrall, Ingrid M; Kruitwagen, Hedwig S; van Wolferen, Monique E; Grinwis, Guy C M; Kummeling, Anne; Rothuizen, Jan; van Velzen, Jeroen F.; Stathonikos, Nikolas; Molenaar, Martijn R; Helms, Bernd J; Brouwers, Jos F H M; Spee, Bart; van Steenbeek, Frank G

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a poorly understood multifactorial pandemic disorder. One of the hallmarks of NAFLD, hepatic steatosis, is a common feature in canine congenital portosystemic shunts. The aim of this study was to gain detailed insight into the pathogenesis of steatosis in

  1. Investigations in enzyme replacement therapy in lipid storage diseases.

    Science.gov (United States)

    Brady, R O; Pentchev, P G; Gal, A G

    1975-04-01

    Enzyme replacement appears to offer much promise as specific therapeutic procedures for patients with Fabry's disease and Gaucher's disease. However, enzyme replacement in patients with Tay-Sachs disease and other heritable metabolic disorders where the central nervous system is affected will require first the development of effective methods for the delivery of exogenous enzymes to the brain; such methods are not yet available.

  2. Adiponectin levels correlate with the severity of hypertriglyceridaemia in glycogen storage disease Ia

    NARCIS (Netherlands)

    Bandsma, R. H. J.; Smit, G. P. A.; Reijngoud, D. -J.; Kuipers, F.

    2009-01-01

    Glycogen storage disease type Ia (GSD Ia) is characterized by severe hypercholesterolaemia and hypertriglyceridaemia. Little is known about the aetiology of the hyperlipidaemia in GSD Ia. Adipokines play an important regulatory role in lipid metabolism. We investigated whether adipokine

  3. Direct and sustained intracellular delivery of exogenous molecules using acoustic-transfection with high frequency ultrasound

    Science.gov (United States)

    Yoon, Sangpil; Kim, Min Gon; Chiu, Chi Tat; Hwang, Jae Youn; Kim, Hyung Ham; Wang, Yingxiao; Shung, K. Kirk

    2016-02-01

    Controlling cell functions for research and therapeutic purposes may open new strategies for the treatment of many diseases. An efficient and safe introduction of membrane impermeable molecules into target cells will provide versatile means to modulate cell fate. We introduce a new transfection technique that utilizes high frequency ultrasound without any contrast agents such as microbubbles, bringing a single-cell level targeting and size-dependent intracellular delivery of macromolecules. The transfection apparatus consists of an ultrasonic transducer with the center frequency of over 150 MHz and an epi-fluorescence microscope, entitled acoustic-transfection system. Acoustic pulses, emitted from an ultrasonic transducer, perturb the lipid bilayer of the cell membrane of a targeted single-cell to induce intracellular delivery of exogenous molecules. Simultaneous live cell imaging using HeLa cells to investigate the intracellular concentration of Ca2+ and propidium iodide (PI) and the delivery of 3 kDa dextran labeled with Alexa 488 were demonstrated. Cytosolic delivery of 3 kDa dextran induced via acoustic-transfection was manifested by diffused fluorescence throughout whole cells. Short-term (6 hr) cell viability test and long-term (40 hr) cell tracking confirmed that the proposed approach has low cell cytotoxicity.

  4. Quality changes of Antarctic krill powder during long term storage

    DEFF Research Database (Denmark)

    Nielsen, Nina Skall; Lu, Henna Fung Sieng; Bruheim, Inge

    2017-01-01

    of packaging in vacuum was observed. The stability was assessed by changes in concentrations of lipid classes, antioxidants, pyrroles and lipid, and Strecker-derived volatiles. Some degradation occurred during storage at room temperature. Thus, a minor increase in volatiles, an increase in free fatty acids...... and a concomitant decrease in antioxidants, tocopherol, and astaxanthin was observed. In addition, there was a minor decrease in phospholipids and n-3 fatty acids; however, storage at vacuum improved the oxidative stability of krill powder. Practical applications: For the use of krill powder in human nutrition......, it is important, that the quality and stability is sufficiently high to retain the nutritional value during storage. This study contributes with information about the stability during storage up to 12 months at room temperature and the effect of packaging the powder in vacuum. Antarctic krill (Euphausia superba...

  5. Comparative genomics and functional study of lipid metabolic genes in Caenorhabditis elegans

    Science.gov (United States)

    2013-01-01

    Background Animal models are indispensable to understand the lipid metabolism and lipid metabolic diseases. Over the last decade, the nematode Caenorhabditis elegans has become a popular animal model for exploring the regulation of lipid metabolism, obesity, and obese-related diseases. However, the genomic and functional conservation of lipid metabolism from C. elegans to humans remains unknown. In the present study, we systematically analyzed genes involved in lipid metabolism in the C. elegans genome using comparative genomics. Results We built a database containing 471 lipid genes from the C. elegans genome, and then assigned most of lipid genes into 16 different lipid metabolic pathways that were integrated into a network. Over 70% of C. elegans lipid genes have human orthologs, with 237 of 471 C. elegans lipid genes being conserved in humans, mice, rats, and Drosophila, of which 71 genes are specifically related to human metabolic diseases. Moreover, RNA-mediated interference (RNAi) was used to disrupt the expression of 356 of 471 lipid genes with available RNAi clones. We found that 21 genes strongly affect fat storage, development, reproduction, and other visible phenotypes, 6 of which have not previously been implicated in the regulation of fat metabolism and other phenotypes. Conclusions This study provides the first systematic genomic insight into lipid metabolism in C. elegans, supporting the use of C. elegans as an increasingly prominent model in the study of metabolic diseases. PMID:23496871

  6. Treatment of Rats with a Self-Selected Hyperlipidic Diet, Increases the Lipid Content of the Main Adipose Tissue Sites in a Proportion Similar to That of the Lipids in the Rest of Organs and Tissues

    Science.gov (United States)

    Romero, María del Mar; Roy, Stéphanie; Pouillot, Karl; Feito, Marisol; Esteve, Montserrat; Grasa, María del Mar; Fernández-López, José-Antonio; Alemany, Marià; Remesar, Xavier

    2014-01-01

    Adipose tissue (AT) is distributed as large differentiated masses, and smaller depots covering vessels, and organs, as well as interspersed within them. The differences between types and size of cells makes AT one of the most disperse and complex organs. Lipid storage is partly shared by other tissues such as muscle and liver. We intended to obtain an approximate estimation of the size of lipid reserves stored outside the main fat depots. Both male and female rats were made overweight by 4-weeks feeding of a cafeteria diet. Total lipid content was analyzed in brain, liver, gastrocnemius muscle, four white AT sites: subcutaneous, perigonadal, retroperitoneal and mesenteric, two brown AT sites (interscapular and perirenal) and in a pool of the rest of organs and tissues (after discarding gut contents). Organ lipid content was estimated and tabulated for each individual rat. Food intake was measured daily. There was a surprisingly high proportion of lipid not accounted for by the main macroscopic AT sites, even when brain, liver and BAT main sites were discounted. Muscle contained about 8% of body lipids, liver 1–1.4%, four white AT sites lipid 28–63% of body lipid, and the rest of the body (including muscle) 38–44%. There was a good correlation between AT lipid and body lipid, but lipid in “other organs” was highly correlated too with body lipid. Brain lipid was not. Irrespective of dietary intake, accumulation of body fat was uniform both for the main lipid storage and handling organs: large masses of AT (but also liver, muscle), as well as in the ”rest” of tissues. These storage sites, in specialized (adipose) or not-specialized (liver, muscle) tissues reacted in parallel against a hyperlipidic diet challenge. We postulate that body lipid stores are handled and regulated coordinately, with a more centralized and overall mechanisms than usually assumed. PMID:24603584

  7. Treatment of rats with a self-selected hyperlipidic diet, increases the lipid content of the main adipose tissue sites in a proportion similar to that of the lipids in the rest of organs and tissues.

    Directory of Open Access Journals (Sweden)

    María Del Mar Romero

    Full Text Available Adipose tissue (AT is distributed as large differentiated masses, and smaller depots covering vessels, and organs, as well as interspersed within them. The differences between types and size of cells makes AT one of the most disperse and complex organs. Lipid storage is partly shared by other tissues such as muscle and liver. We intended to obtain an approximate estimation of the size of lipid reserves stored outside the main fat depots. Both male and female rats were made overweight by 4-weeks feeding of a cafeteria diet. Total lipid content was analyzed in brain, liver, gastrocnemius muscle, four white AT sites: subcutaneous, perigonadal, retroperitoneal and mesenteric, two brown AT sites (interscapular and perirenal and in a pool of the rest of organs and tissues (after discarding gut contents. Organ lipid content was estimated and tabulated for each individual rat. Food intake was measured daily. There was a surprisingly high proportion of lipid not accounted for by the main macroscopic AT sites, even when brain, liver and BAT main sites were discounted. Muscle contained about 8% of body lipids, liver 1-1.4%, four white AT sites lipid 28-63% of body lipid, and the rest of the body (including muscle 38-44%. There was a good correlation between AT lipid and body lipid, but lipid in "other organs" was highly correlated too with body lipid. Brain lipid was not. Irrespective of dietary intake, accumulation of body fat was uniform both for the main lipid storage and handling organs: large masses of AT (but also liver, muscle, as well as in the "rest" of tissues. These storage sites, in specialized (adipose or not-specialized (liver, muscle tissues reacted in parallel against a hyperlipidic diet challenge. We postulate that body lipid stores are handled and regulated coordinately, with a more centralized and overall mechanisms than usually assumed.

  8. Cytoskeletal Network Morphology Regulates Intracellular Transport Dynamics

    Science.gov (United States)

    Ando, David; Korabel, Nickolay; Huang, Kerwyn Casey; Gopinathan, Ajay

    2015-01-01

    Intracellular transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable timescales, the topological features of the cytoskeletal network that regulate transport efficiency and robustness have not been established. Using a continuum diffusion model, we observed that the time required for cellular transport was minimized when the network was localized near the nucleus. In simulations that explicitly incorporated network spatial architectures, total filament mass was the primary driver of network transit times. However, filament traps that redirect cargo back to the nucleus caused large variations in network transport. Filament polarity was more important than filament orientation in reducing average transit times, and transport properties were optimized in networks with intermediate motor on and off rates. Our results provide important insights into the functional constraints on intracellular transport under which cells have evolved cytoskeletal structures, and have potential applications for enhancing reactions in biomimetic systems through rational transport network design. PMID:26488648

  9. Intracellular bacteria: the origin of dinoflagellate toxicity.

    Science.gov (United States)

    Silva, E S

    1990-01-01

    Dinoflagellate blooms of the same species have been registered either as toxic or nontoxic and, in the latter case, toxicity may be of different types. A hypothesis has been formulated according to which the bacteria having in some way taken part in the toxin formation are either inside the dinoflagellate cell or in the nutritive liquid. The presence of intracellular bacteria in those microorganisms has been studied mainly in material from cultures, a few from the sea, and several strains were isolated from different species. Experiments with crossed inoculations have shown that the bacterial strain from Gonyaulax tamarensis caused the cells of some other species to become toxic. From nontoxic clonal cultures of Prorocentrum balticum, Glenodinium foliaceum, and Gyrodinium instriatum, after inoculation of that bacterial strain, cultures were obtained whose cell extracts showed the same kind of toxicity as G. tamarensis. No toxic action could be found in the extracts of the bacterial cells form the assayed strains. The interference of intracellular bacteria in the metabolism of dinoflagellates must be the main cause of their toxicity.

  10. Cytoskeletal Network Morphology Regulates Intracellular Transport Dynamics.

    Science.gov (United States)

    Ando, David; Korabel, Nickolay; Huang, Kerwyn Casey; Gopinathan, Ajay

    2015-10-20

    Intracellular transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable timescales, the topological features of the cytoskeletal network that regulate transport efficiency and robustness have not been established. Using a continuum diffusion model, we observed that the time required for cellular transport was minimized when the network was localized near the nucleus. In simulations that explicitly incorporated network spatial architectures, total filament mass was the primary driver of network transit times. However, filament traps that redirect cargo back to the nucleus caused large variations in network transport. Filament polarity was more important than filament orientation in reducing average transit times, and transport properties were optimized in networks with intermediate motor on and off rates. Our results provide important insights into the functional constraints on intracellular transport under which cells have evolved cytoskeletal structures, and have potential applications for enhancing reactions in biomimetic systems through rational transport network design. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Intracellular accumulation of norfloxacin in Mycobacterium smegmatis.

    Science.gov (United States)

    Corti, S; Chevalier, J; Cremieux, A

    1995-01-01

    To evaluate the intracellular accumulation of norfloxacin in mycobacteria, two methods were used with Mycobacterium smegmatis. A radiometric method (K. V. Cundy, C. E. Fasching, K. E. Willard, and L. R. Peterson, J. Antimicrob. Chemother. 28:491-497, 1991) was used without great modification, but the fluorometric method (P. G. S. Mortimer and L. J. V. Piddock, J. Antimicrob. Chemother. 28:639-653, 1991) was changed considerably. Indeed, adsorption of the quinolone to the bacterial surface was characterized by measuring the level of accumulation of 0 degree C. Taking into account the adsorption, the pH of the washing buffer was increased from 7.0 to 9.0 to improve the desorption of norfloxacin from the cell surface. Both the fluorometric method, with the technical improvement, and the radiometric method could be used to estimate the intracellular accumulation of norfloxacin, which resulted from the difference between the whole uptake measured at 37 degrees C and the adsorption measured at 0 degrees C. A total of 35 ng of norfloxacin per mg of cells (dry weight) penetrated into the M. smegmatis cell, and the steady state was achieved in 5 min. Use of inhibitors of the proton motive force revealed that transport of norfloxacin was energy independent. Thus, the same mechanisms of quinolone accumulation that occur in eubacteria seem to occur in mycobacteria, at least in M. smegmatis. PMID:8585727

  12. Fluorescent nanoparticles for intracellular sensing: a review.

    Science.gov (United States)

    Ruedas-Rama, Maria J; Walters, Jamie D; Orte, Angel; Hall, Elizabeth A H

    2012-11-02

    Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. [Intracellular signaling mechanisms in thyroid cancer].

    Science.gov (United States)

    Mondragón-Terán, Paul; López-Hernández, Luz Berenice; Gutiérrez-Salinas, José; Suárez-Cuenca, Juan Antonio; Luna-Ceballos, Rosa Isela; Erazo Valle-Solís, Aura

    2016-01-01

    Thyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated» (MAPK) which consist of «modules» of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis. To review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer. Molecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  14. Stochastic models of intracellular calcium signals

    Energy Technology Data Exchange (ETDEWEB)

    Rüdiger, Sten, E-mail: sten.ruediger@physik.hu-berlin.de

    2014-01-10

    Cellular signaling operates in a noisy environment shaped by low molecular concentrations and cellular heterogeneity. For calcium release through intracellular channels–one of the most important cellular signaling mechanisms–feedback by liberated calcium endows fluctuations with critical functions in signal generation and formation. In this review it is first described, under which general conditions the environment makes stochasticity relevant, and which conditions allow approximating or deterministic equations. This analysis provides a framework, in which one can deduce an efficient hybrid description combining stochastic and deterministic evolution laws. Within the hybrid approach, Markov chains model gating of channels, while the concentrations of calcium and calcium binding molecules (buffers) are described by reaction–diffusion equations. The article further focuses on the spatial representation of subcellular calcium domains related to intracellular calcium channels. It presents analysis for single channels and clusters of channels and reviews the effects of buffers on the calcium release. For clustered channels, we discuss the application and validity of coarse-graining as well as approaches based on continuous gating variables (Fokker–Planck and chemical Langevin equations). Comparison with recent experiments substantiates the stochastic and spatial approach, identifies minimal requirements for a realistic modeling, and facilitates an understanding of collective channel behavior. At the end of the review, implications of stochastic and local modeling for the generation and properties of cell-wide release and the integration of calcium dynamics into cellular signaling models are discussed.

  15. Detection of Lipid-Rich Prostate Circulating Tumour Cells with Coherent Anti-Stokes Raman Scattering Microscopy

    International Nuclear Information System (INIS)

    Mitra, Ranjana; Chao, Olivia; Urasaki, Yasuyo; Goodman, Oscar B; Le, Thuc T

    2012-01-01

    Circulating tumour cells (CTC) are an important indicator of metastasis and associated with a poor prognosis. Detection sensitivity and specificity of CTC in the peripheral blood of metastatic cancer patient remain a technical challenge. Coherent anti-Stokes Raman scattering (CARS) microscopy was employed to examine the lipid content of CTC isolated from the peripheral blood of metastatic prostate cancer patients. CARS microscopy was also employed to evaluate lipid uptake and mobilization kinetics of a metastatic human prostate cancer cell line. One hundred CTC from eight metastatic prostate cancer patients exhibited strong CARS signal which arose from intracellular lipid. In contrast, leukocytes exhibited weak CARS signal which arose mostly from cellular membrane. On average, CARS signal intensity of prostate CTC was 7-fold higher than that of leukocytes (P<0.0000001). When incubated with human plasma, C4-2 metastatic human prostate cancer cells exhibited rapid lipid uptake kinetics and slow lipid mobilization kinetics. Higher expression of lipid transport proteins in C4-2 cells compared to non-transformed RWPE-1 and non-malignant BPH-1 prostate epithelial cells further indicated strong affinity for lipid of metastatic prostate cancer cells. Intracellular lipid could serve as a biomarker for prostate CTC which could be sensitively detected with CARS microscopy in a label-free manner. Strong affinity for lipid by metastatic prostate cancer cells could be used to improve detection sensitivity and therapeutic targeting of prostate CTC

  16. Membrane contact sites, ancient and central hubs of cellular lipid logistics.

    Science.gov (United States)

    Jain, Amrita; Holthuis, Joost C M

    2017-09-01

    Membrane contact sites (MCSs) are regions where two organelles are closely apposed to facilitate molecular communication and promote a functional integration of compartmentalized cellular processes. There is growing evidence that MCSs play key roles in controlling intracellular lipid flows and distributions. Strikingly, even organelles connected by vesicular trafficking exchange lipids en bulk via lipid transfer proteins that operate at MCSs. Herein, we describe how MCSs developed into central hubs of lipid logistics during the evolution of eukaryotic cells. We then focus on how modern eukaryotes exploit MCSs to help solve a major logistical problem, namely to preserve the unique lipid mixtures of their early and late secretory organelles in the face of extensive vesicular trafficking. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann. Copyright © 2017. Published by Elsevier B.V.

  17. How can lipid nanocarriers improve transdermal delivery of olanzapine?

    Science.gov (United States)

    Iqbal, Nimra; Vitorino, Carla; Taylor, Kevin M G

    2017-06-01

    The development of a transdermal nanocarrier drug delivery system with potential for the treatment of psychiatric disorders, such as schizophrenia and bipolar disorder, is described. Lipid nanocarriers (LN), encompassing various solid:liquid lipid compositions were formulated and assessed as potential nanosystems for transdermal delivery of olanzapine. A previously optimized method of hot high pressure homogenization (HPH) was adopted for the production of the LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Precirol  ® was selected as the solid lipid for progression of studies. SLN exhibited the best performance for transdermal delivery of olanzapine, based on in vitro release and permeation studies, coupled with results from physicochemical characterization of several solid:liquid lipid formulations. Stability tests, performed to give an indication of long-term storage behavior of the formulations, were in good agreement with previous studies for the best choice of solid:liquid lipid ratio. Overall, these findings highlight the SLN-based formulation as promising for the further inclusion in and production of transdermal patches, representing an innovative therapeutic approach.

  18. Intracellular signaling by diffusion: can waves of hydrogen peroxide transmit intracellular information in plant cells?

    DEFF Research Database (Denmark)

    Vestergaard, Christian L.; Flyvbjerg, Henrik; Møller, Ian Max

    2012-01-01

    Amplitude- and frequency-modulated waves of Ca(2+) ions transmit information inside cells. Reactive Oxygen Species (ROS), specifically hydrogen peroxide, have been proposed to have a similar role in plant cells. We consider the feasibility of such an intracellular communication system in view...

  19. Interfacial Tension and Surface Pressure of High Density Lipoprotein, Low Density Lipoprotein, and Related Lipid Droplets

    DEFF Research Database (Denmark)

    Ollila, O. H. S.; Lamberg, A.; Lehtivaara, M.

    2012-01-01

    Lipid droplets play a central role in energy storage and metabolism on a cellular scale. Their core is comprised of hydrophobic lipids covered by a surface region consisting of amphiphilic lipids and proteins. For example, high and low density lipoproteins (HDL and LDL, respectively....... Here we use coarse-grained molecular-dynamics simulations to consider a number of related issues by calculating the interfacial tension in protein-free lipid droplets, and in HDL and LDL particles mimicking physiological conditions. First, our results suggest that the curvature dependence...

  20. Lipids, lipid bilayers and vesicles as seen by neutrons

    International Nuclear Information System (INIS)

    Seto, Hideki

    2011-01-01

    Lipid molecules self-assemble into bilayers in water with their hydrocarbon chains facing inward due to their amphiphilic nature. The structural and dynamical properties of lipids and lipid bilayers have been studied by neutron scattering intensively. In this article, 3 topics are shown as typical examples. 1) a time-resolved small-angle neutron scattering on uni-lamellar vesicles composed of deuterated and protonated lipids to determine lipid kinetics, 2) small-angle neutron scattering to investigate spontaneous formation of nanopores on uni-lamellar vesicles, and 3) neutron spin echo study to determine bending modulus of lipid bilayers. (author)

  1. 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

  2. The effects of feed composition on the sensory quality of organic rainbow trout during ice storage

    DEFF Research Database (Denmark)

    Green-Pedersen, Ditte; Hyldig, Grethe; Jacobsen, Charlotte

    fishmeal and a mixture of protein from organic vegetable, while the lipid sources were fish oil and organic oil from linseed, sunflower, rapeseed and grape seed. Sensory analysis was performed after 3, 5, 7 and 14 days of storage in ice. The results showed that both protein and lipid source in the feed can...

  3. Liquid Cloud Storage

    OpenAIRE

    Luby, Michael G.; Padovani, Roberto; Richardson, Thomas J.; Minder, Lorenz; Aggarwal, Pooja

    2017-01-01

    A liquid system provides durable object storage based on spreading redundantly generated data across a network of hundreds to thousands of potentially unreliable storage nodes. A liquid system uses a combination of a large code, lazy repair, and a flow storage organization. We show that a liquid system can be operated to enable flexible and essentially optimal combinations of storage durability, storage overhead, repair bandwidth usage, and access performance.

  4. Age-associated intracellular superoxide dismutase deficiency potentiates dermal fibroblast dysfunction during wound healing.

    Science.gov (United States)

    Fujiwara, Toshihiro; Dohi, Teruyuki; Maan, Zeshaan N; Rustad, Kristine C; Kwon, Sun Hyung; Padmanabhan, Jagannath; Whittam, Alexander J; Suga, Hirotaka; Duscher, Dominik; Rodrigues, Melanie; Gurtner, Geoffrey C

    2017-07-04

    Reactive oxygen species (ROS) impair wound healing through destructive oxidation of intracellular proteins, lipids and nucleic acids. Intracellular superoxide dismutase (SOD1) regulates ROS levels and plays a critical role in tissue homoeostasis. Recent evidence suggests that age-associated wound healing impairments may partially result from decreased SOD1 expression. We investigated the mechanistic basis by which increased oxidative stress links to age-associated impaired wound healing. Fibroblasts were isolated from unwounded skin of young and aged mice, and myofibroblast differentiation was assessed by measuring α-smooth muscle actin and collagen gel contraction. Excisional wounds were created on young and aged mice to study the healing rate, ROS levels and SOD1 expression. A mechanistic link between oxidative stress and fibroblast function was explored by assessing the TGF-β1 signalling pathway components in young and aged mice. Age-related wounds displayed reduced myofibroblast differentiation and delayed wound healing, consistent with a decrease in the in vitro capacity for fibroblast-myofibroblast transition following oxidative stress. Young fibroblasts with normal SOD1 expression exhibited increased phosphorylation of ERK in response to elevated ROS. In contrast, aged fibroblasts with reduced SOD1 expression displayed a reduced capacity to modulate intracellular ROS. Collectively, age-associated wound healing impairments are associated with fibroblast dysfunction that is likely the result of decreased SOD1 expression and subsequent dysregulation of intracellular ROS. Strategies targeting these mechanisms may suggest a new therapeutic approach in the treatment of chronic non-healing wounds in the aged population. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. 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. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Intracellular pH in sperm physiology.

    Science.gov (United States)

    Nishigaki, Takuya; José, Omar; González-Cota, Ana Laura; Romero, Francisco; Treviño, Claudia L; Darszon, Alberto

    2014-08-01

    Intracellular pH (pHi) regulation is essential for cell function. Notably, several unique sperm ion transporters and enzymes whose elimination causes infertility are either pHi dependent or somehow related to pHi regulation. Amongst them are: CatSper, a Ca(2+) channel; Slo3, a K(+) channel; the sperm-specific Na(+)/H(+) exchanger and the soluble adenylyl cyclase. It is thus clear that pHi regulation is of the utmost importance for sperm physiology. This review briefly summarizes the key components involved in pHi regulation, their characteristics and participation in fundamental sperm functions such as motility, maturation and the acrosome reaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Drosophila VAMP7 regulates Wingless intracellular trafficking.

    Science.gov (United States)

    Gao, Han; He, Fang; Lin, Xinhua; Wu, Yihui

    2017-01-01

    Drosophila Wingless (Wg) is a morphogen that determines cell fate during development. Previous studies have shown that endocytic pathways regulate Wg trafficking and signaling. Here, we showed that loss of vamp7, a gene required for vesicle fusion, dramatically increased Wg levels and decreased Wg signaling. Interestingly, we found that levels of Dally-like (Dlp), a glypican that can interact with Wg to suppress Wg signaling at the dorsoventral boundary of the Drosophila wing, were also increased in vamp7 mutant cells. Moreover, Wg puncta in Rab4-dependent recycling endosomes were Dlp positive. We hypothesize that VAMP7 is required for Wg intracellular trafficking and the accumulation of Wg in Rab4-dependent recycling endosomes might affect Wg signaling.

  8. Intracellular Signalling by C-Peptide

    Directory of Open Access Journals (Sweden)

    Claire E. Hills

    2008-01-01

    Full Text Available C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na+/K+ ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes.

  9. Intracellular Na⁺ and cardiac metabolism.

    Science.gov (United States)

    Bay, Johannes; Kohlhaas, Michael; Maack, Christoph

    2013-08-01

    In heart failure, alterations of excitation-contraction underlie contractile dysfunction. One important defect is an elevation of the intracellular Na(+) concentration in cardiac myocytes ([Na(+)]i), which has an important impact on cytosolic and mitochondrial Ca(2+) homeostasis. While elevated [Na(+)]i is thought to compensate for decreased Ca(2+) load of the sarcoplasmic reticulum (SR), it yet negatively affects energy supply-and-demand matching and can even induce mitochondrial oxidative stress. Here, we review the mechanisms underlying these pathophysiological changes. The chain of events may constitute a vicious cycle of ion dysregulation, oxidative stress and energetic deficit, resembling characteristic cellular deficits that are considered key hallmarks of the failing heart. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes". Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. An intracellular anion channel critical for pigmentation.

    Science.gov (United States)

    Bellono, Nicholas W; Escobar, Iliana E; Lefkovith, Ariel J; Marks, Michael S; Oancea, Elena

    2014-12-16

    Intracellular ion channels are essential regulators of organellar and cellular function, yet the molecular identity and physiological role of many of these channels remains elusive. In particular, no ion channel has been characterized in melanosomes, organelles that produce and store the major mammalian pigment melanin. Defects in melanosome function cause albinism, characterized by vision and pigmentation deficits, impaired retinal development, and increased susceptibility to skin and eye cancers. The most common form of albinism is caused by mutations in oculocutaneous albinism II (OCA2), a melanosome-specific transmembrane protein with unknown function. Here we used direct patch-clamp of skin and eye melanosomes to identify a novel chloride-selective anion conductance mediated by OCA2 and required for melanin production. Expression of OCA2 increases organelle pH, suggesting that the chloride channel might regulate melanin synthesis by modulating melanosome pH. Thus, a melanosomal anion channel that requires OCA2 is essential for skin and eye pigmentation.

  11. Nanobodies: Chemical Functionalization Strategies and Intracellular Applications

    Science.gov (United States)

    Schumacher, Dominik; Helma, Jonas; Schneider, Anselm F. L.; Leonhardt, Heinrich

    2018-01-01

    Abstract Nanobodies can be seen as next‐generation tools for the recognition and modulation of antigens that are inaccessible to conventional antibodies. Due to their compact structure and high stability, nanobodies see frequent usage in basic research, and their chemical functionalization opens the way towards promising diagnostic and therapeutic applications. In this Review, central aspects of nanobody functionalization are presented, together with selected applications. While early conjugation strategies relied on the random modification of natural amino acids, more recent studies have focused on the site‐specific attachment of functional moieties. Such techniques include chemoenzymatic approaches, expressed protein ligation, and amber suppression in combination with bioorthogonal modification strategies. Recent applications range from sophisticated imaging and mass spectrometry to the delivery of nanobodies into living cells for the visualization and manipulation of intracellular antigens. PMID:28913971

  12. Lipid peroxidation in bovine semen.

    Science.gov (United States)

    Dawra, R K; Sharma, O P; Makkar, H P

    1983-01-01

    Bovine whole semen, spermatozoa, and seminal plasma did not undergo lipid peroxidation when aerobically incubated. However, lipid peroxidation was induced in washed spermatozoa in the presence of iron or iron plus sodium ascorbate, whereas heating, sonication, or treatment with proteolytic enzymes did not have any effect. The time required for formation of optimum concentration of lipid peroxides in washed spermatozoa is very short as compared to other systems. Lipid peroxides are entirely contributed by the lipid fraction of spermatozoa. Formation of lipid peroxides is completely inhibited by the presence of seminal plasma in incubation mixture.

  13. Progestin modulates the lipid profile and sensitivity of breast cancer cells to docetaxel

    Science.gov (United States)

    Schlaepfer, Isabel R.; Hitz, Carolyn A.; Gijón, Miguel A.; Bergman, Bryan C.; Eckel, Robert H.; Jacobsen, Britta M.

    2015-01-01

    Progestins induce lipid accumulation in progesterone receptor (PR)-positive breast cancer cells. We speculated that progestin-induced alterations in lipid biology confer resistance to chemotherapy. To examine the biology of lipid loaded breast cancer cells, we used a model of progestin-induced lipid synthesis. T47D (PR-positive) and MDA-MB-231(PR-negative) cell lines were used to study progestin response. Oil red O staining of T47D cells treated with progestin showed lipid droplet formation was PR dependent, glucose dependent and reduced sensitivity to docetaxel. This protection was not observed in PR-negative MDA-MB-231 cells. Progestin treatment induced stearoyl CoA desaturase-1 (SCD-1) enzyme expression and chemical inhibition of SCD-1 diminished lipid droplets and cell viability, suggesting the importance of lipid stores in cancer cell survival. Gas chromatography/mass spectroscopy analysis of phospholipids from progestin-treated T47D cells revealed an increase in unsaturated fatty acids, with oleic acid as most abundant. Cells surviving docetaxel treatment also contained more oleic acid in phospholipids, suggesting altered membrane fluidity as a potential mechanism of chemoresistance mediated in part by SCD-1. Lastly, intact docetaxel molecules were present within progestin induced lipid droplets, suggesting a protective quenching effect of intracellular lipid droplets. Our studies suggest the metabolic adaptations produced by progestin provide novel metabolic targets for future combinatorial therapies for progestin-responsive breast cancers. PMID:22922095

  14. Synthesis, activity, and structure--activity relationship studies of novel cationic lipids for DNA transfer.

    Science.gov (United States)

    Byk, G; Dubertret, C; Escriou, V; Frederic, M; Jaslin, G; Rangara, R; Pitard, B; Crouzet, J; Wils, P; Schwartz, B; Scherman, D

    1998-01-15

    We have designed and synthesized original cationic lipids for gene delivery. A synthetic method on solid support allowed easy access to unsymmetrically monofunctionalized polyamine building blocks of variable geometries. These polyamine building blocks were introduced into cationic lipids. To optimize the transfection efficiency in the novel series, we have carried out structure-activity relationship studies by introduction of variable-length lipids, of variable-length linkers between lipid and cationic moiety, and of substituted linkers. We introduce the concept of using the linkers within cationic lipids molecules as carriers of side groups harboring various functionalities (side chain entity), as assessed by the introduction of a library composed of cationic entities, additional lipid chains, targeting groups, and finally the molecular probes rhodamine and biotin for cellular traffic studies. The transfection activity of the products was assayed in vitro on Hela carcinoma, on NIH3T3, and on CV1 fibroblasts and in vivo on the Lewis Lung carcinoma model. Products from the series displayed high transfection activities. Results indicated that the introduction of a targeting side chain moiety into the cationic lipid is permitted. A primary physicochemical characterization of the DNA/lipid complexes was demonstrated with this leading compound. Selected products from the series are currently being developed for preclinical studies, and the labeled lipopolyamines can be used to study the intracellular traffic of DNA/cationic lipid complexes.

  15. Detection and imaging of lipids ofScenedesmus obliquusbased on confocal Raman microspectroscopy.

    Science.gov (United States)

    Shao, Yongni; Fang, Hui; Zhou, Hong; Wang, Qi; Zhu, Yiming; He, Yong

    2017-01-01

    In this study, confocal Raman microspectroscopy was used to detect lipids in microalgae rapidly and non-destructively. Microalgae cells were cultured under nitrogen deficiency. The accumulation of lipids in Scenedesmus obliquus was observed by Nile red staining, and the total amount of lipids accumulated in the cells was measured by gravimetric method. The signals from different microalgae cells were collected by confocal Raman microspectroscopy to establish a prediction model of intracellular lipid content, and surface scanning signals for drawing pseudo color images of lipids distribution. The images can show the location of pyrenoid and lipid accumulation in cells. Analyze Raman spectrum data and build PCA-LDA model using four different bands (full bands, pigments, lipids, and mixed features). Models of full bands or pigment characteristic bands were capable of identifying S. obliquus cells under different nitrogen stress culture time. The prediction accuracy of model of lipid characteristic bands is relatively low. The correlation between the fatty acid content measured by the gravimetric method and the integral Raman intensity of the oil characteristic peak (1445 cm -1 ) measured by Raman spectroscopy was analyzed. There was significant correlation ( R 2  = 0.83), which means that Raman spectroscopy is applicable to semi-quantitative detection of microalgal lipid content.

  16. Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis

    International Nuclear Information System (INIS)

    Le, Thuc T; Huff, Terry B; Cheng, Ji-Xin

    2009-01-01

    Lipid-rich tumours have been associated with increased cancer metastasis and aggressive clinical behaviours. Nonetheless, pathologists cannot classify lipid-rich tumours as a clinically distinctive form of carcinoma due to a lack of mechanistic understanding on the roles of lipids in cancer development. Coherent anti-Stokes Raman scattering (CARS) microscopy is employed to study cancer cell behaviours in excess lipid environments in vivo and in vitro. The impacts of a high fat diet on cancer development are evaluated in a Balb/c mice cancer model. Intravital flow cytometry and histology are employed to enumerate cancer cell escape to the bloodstream and metastasis to lung tissues, respectively. Cancer cell motility and tissue invasion capability are also evaluated in excess lipid environments. CARS imaging reveals intracellular lipid accumulation is induced by excess free fatty acids (FFAs). Excess FFAs incorporation onto cancer cell membrane induces membrane phase separation, reduces cell-cell contact, increases surface adhesion, and promotes tissue invasion. Increased plasma FFAs level and visceral adiposity are associated with early rise in circulating tumour cells and increased lung metastasis. Furthermore, CARS imaging reveals FFAs-induced lipid accumulation in primary, circulating, and metastasized cancer cells. Lipid-rich tumours are linked to cancer metastasis through FFAs-induced physical perturbations on cancer cell membrane. Most importantly, the revelation of lipid-rich circulating tumour cells suggests possible development of CARS intravital flow cytometry for label-free detection of early-stage cancer metastasis

  17. 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

  18. Niemann-Pick type C mutations cause lipid traffic jam.

    Science.gov (United States)

    Liscum, L

    2000-03-01

    The Niemann-Pick C protein (NPC1) is required for cholesterol transport from late endosomes and lysosomes to other cellular membranes. Mutations in NPC1 cause lysosomal lipid storage and progressive neurological degeneration. Cloning of the NPC1 gene has given us tools with which to investigate the function of this putative cholesterol transporter. Here, we discuss recent studies indicating that NPC1 is not a cholesterol-specific transport molecule. Instead, NPC1 appears to be required for the vesicular shuttling of both lipids and fluid-phase constituents from multivesicular late endosomes to destinations such as the trans-Golgi network.

  19. Preparation and characterization of solid lipid nanoparticles containing silibinin.

    Science.gov (United States)

    Zhang, J Q; Liu, J; Li, X L; Jasti, B R

    2007-08-01

    The study describes the development of stealth solid lipid nanoparticles (SLNs) as colloidal carriers for silibinin, a drug with very low solubility. Stealth SLNs were constituted mainly of bioacceptable and biodegradable lipids, such as stearic acid and surfactant Brij 78 (polyoxyethylene 20 stearyl ether) and can incorporate amounts of silibinin up to 7.55%. Stealth-loaded SLNs were in the nanometer size range. Thermal analysis (differential scanning calorimetry) showed that silibinin was dispersed in the stealth SLNs at an amorphous state. Release of silibinin from stealth SLNs was very slow. Stealth SLNs were stable without precipitation of silibinin on storage conditions and can be proposed for their parenteral administration.

  20. Investigation of Intracellular Free Ca2+ Concentration Dynamics with Fluorescence Methods

    Directory of Open Access Journals (Sweden)

    Figen Cicek

    2016-09-01

    Full Text Available Most of the extracellular stimulus arrive to the cell membrane result with the increase in cytoplasmic free Ca2+ concentration [Ca2+]i. Because of the huge Ca2+ concentration differences between the cytoplasm ( and #8776;10-7 M and extracellular fluid and endoplasmic reticulum (ER - which is the major Ca2+ storage organelle in especially non electrically excitable cells ( and #8776;10-3 M, a large electro-chemical gradient repel Ca2+ to the plasma or ER. Therefore a signal which temporarily opens Ca2+ channels, induce a fast influx of Ca2+ through the cytosol and increase the its concentration about 10-20 fold. At this organization free Ca2+ functions as a intracellular signalling molecule and a second messenger. In this way many intracellular signalling proteins activated and cellular functions like gene expression, secretion, cell proliferation and division, apoptosis, and also myocyte contraction, endocrine cell degranulation and neuronal transmission are regulated. Thus, the key role of Ca2+ in many intracellular process, makes the dynamic measurements necessary for an understanding of the signalling mechanisms. Fluorescence imaging techniques make possible of monitoring the spatiotemporal Ca2+ response patterns in cytoplasm. In the last decades, especially their ease of loading, and minimum manipulations to the cell homeostasis, make these techniques unique with respect to the other methods. [Archives Medical Review Journal 2016; 25(3.000: 319-334

  1. Synthesis of deuterium-labeled analogs of the lipid hydroperoxide-derived bifunctional electrophile 4-oxo-2(E)-nonenal

    OpenAIRE

    Arora, Jasbir S.; Oe, Tomoyuki; Blair, Ian A.

    2011-01-01

    Lipid hydroperoxides undergo homolytic decomposition into the bifunctional 4-hydroxy-2(E)-nonenal and 4-oxo-2(E)-nonenal (ONE). These bifunctional electrophiles are highly reactive and can readily modify intracellular molecules including glutathione (GSH), deoxyribonucleic acid (DNA) and proteins. Lipid hydroperoxide-derived bifunctional electrophiles are thought to contribute to the pathogenesis of a number of diseases. ONE is an α,β-unsaturated aldehyde that can react in multiple ways and w...

  2. The Oleaginous Yeast Meyerozyma guilliermondii BI281A as a New Potential Biodiesel Feedstock: Selection and Lipid Production Optimization

    Directory of Open Access Journals (Sweden)

    Mauricio Ramírez-Castrillón

    2017-09-01

    Full Text Available A high throughput screening (HTS methodology for evaluation of cellular lipid content based on Nile red fluorescence reads using black background 96-wells test plates and a plate reader equipment allowed the rapid intracellular lipid estimation of strains from a Brazilian phylloplane yeast collection. A new oleaginous yeast, Meyerozyma guilliermondii BI281A, was selected, for which the gravimetric determination of total lipids relative to dry weight was 52.38% for glucose or 34.97% for pure glycerol. The lipid production was optimized obtaining 108 mg/L of neutral lipids using pure glycerol as carbon source, and the strain proved capable of accumulating oil using raw glycerol from a biodiesel refinery. The lipid profile showed monounsaturated fatty acids (MUFA varying between 56 or 74% in pure or raw glycerol, respectively. M. guilliermondii BI281A bears potential as a new biodiesel feedstock.

  3. The Oleaginous Yeast Meyerozyma guilliermondii BI281A as a New Potential Biodiesel Feedstock: Selection and Lipid Production Optimization.

    Science.gov (United States)

    Ramírez-Castrillón, Mauricio; Jaramillo-Garcia, Victoria P; Rosa, Priscila D; Landell, Melissa F; Vu, Duong; Fabricio, Mariana F; Ayub, Marco A Z; Robert, Vincent; Henriques, João A P; Valente, Patricia

    2017-01-01

    A high throughput screening (HTS) methodology for evaluation of cellular lipid content based on Nile red fluorescence reads using black background 96-wells test plates and a plate reader equipment allowed the rapid intracellular lipid estimation of strains from a Brazilian phylloplane yeast collection. A new oleaginous yeast, Meyerozyma guilliermondii BI281A, was selected, for which the gravimetric determination of total lipids relative to dry weight was 52.38% for glucose or 34.97% for pure glycerol. The lipid production was optimized obtaining 108 mg/L of neutral lipids using pure glycerol as carbon source, and the strain proved capable of accumulating oil using raw glycerol from a biodiesel refinery. The lipid profile showed monounsaturated fatty acids (MUFA) varying between 56 or 74% in pure or raw glycerol, respectively. M. guilliermondii BI281A bears potential as a new biodiesel feedstock.

  4. Strategies of Intracellular Pathogens for Obtaining Iron from the Environment

    Directory of Open Access Journals (Sweden)

    Nidia Leon-Sicairos

    2015-01-01

    Full Text Available Most microorganisms are destroyed by the host tissues through processes that usually involve phagocytosis and lysosomal disruption. However, some organisms, called intracellular pathogens, are capable of avoiding destruction by growing inside macrophages or other cells. During infection with intracellular pathogenic microorganisms, the element iron is required by both the host cell and the pathogen that inhabits the host cell. This minireview focuses on how intracellular pathogens use multiple strategies to obtain nutritional iron from the intracellular environment in order to use this element for replication. Additionally, the implications of these mechanisms for iron acquisition in the pathogen-host relationship are discussed.

  5. Cell-based lipid flippase assay employing fluorescent lipid derivatives

    DEFF Research Database (Denmark)

    Jensen, Maria Stumph; Costa, Sara; Günther-Pomorski, Thomas

    2016-01-01

    , studies of individual P4-ATPase family members from fungi, plants, and animals show that P4-ATPases differ in their substrate specificities and mediate transport of a broader range of lipid substrates. Here, we describe an assay based on fluorescent lipid derivatives to monitor and characterize lipid...

  6. Lipids in airway secretions

    International Nuclear Information System (INIS)

    Bhaskar, K.R.; DeFeudis O'Sullivan, D.; Opaskar-Hincman, H.; Reid, L.M.

    1987-01-01

    Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO 2 , (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors 14 C acetate and 14 C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway. (author)

  7. DISTURBANCES OF LIPID METABOLISM

    Directory of Open Access Journals (Sweden)

    P. F. Litvitskii

    2012-01-01

    Full Text Available The article contains modern data on etiology, pathogenesis, manifestations and mechanisms of development of the most common forms of lipid metabolism disturbances in humans, such as obesity, emaciation, lipodystrophy, lipidosis, dyslipoproteinemia and atherosclerosis. The authors give the informative materials for self-testing and correction of the knowledge level.

  8. Exogenous lipid pneumonia

    International Nuclear Information System (INIS)

    Bernasconi, A.; Gavelli, G.; Zompatori, M.; Galleri, C.; Zanasi, A.; Fabbri, M.; Bazzocchi, F.

    1988-01-01

    Exogenous lipid pneumonia (ELP) is caused by the aspiration of animal, vegetal or, more often, mineral oils. Even though it may also be acute, ELP is most frequently a chronic disease, affecting people with predisposing factors, such as neuromuscular disorders, structural abnormalities and so on; very often exogenous lipid pneumonia is found in tracheotomized patients. The pathology of lipid pneumonia is a chronic inflammatory process evolving in foreign-body-like reaction, and eventually in ''end-stage lung'' condition. Clinically, most patients are asymptomatic; few cases only present with cough, dyspnea and chest pain. Eight cases of ELP, studied over the past 3 years, are described in this paper. All the patients were examined by chest radiographs and standard tomograms; 3 patients underwent CT. X-ray features were mono/bilateral consolidation of the lower zones, with air bronchogram and variable reduction in volume. CT density was not specific for fat tissue. In all cases the diagnosis was confirmed at biopsy. In 5 patients, followed for at least one year, clinical-radiological features showed no change. Thus, complications of ELP (especially malignant evolution) could be excluded. The authors conclude that lipid pneumonia must be considered in differential diagnosis of patients with history of usage of oils and compatible X-ray findings. The usefulness of an accurate follow-up is stressed

  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

    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

  11. 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

  12. 443 Review Lipids

    African Journals Online (AJOL)

    Marinda

    2009-07-20

    Jul 20, 2009 ... mitochondrial long-chain fatty acid transport occurred in isolated ... be related to cardiac preference for lipid compared to the brain's preference for carbohydrates as fuel sources.32 It may also explain ... only short- and medium-chain fatty acids (length) can enter mitochondria by passive diffusion. STEP 1.

  13. Salivary lipids: A review.

    Science.gov (United States)

    Matczuk, Jan; Żendzian-Piotrowska, Małgorzata; Maciejczyk, Mateusz; Kurek, Krzysztof

    2017-09-01

    Saliva is produced by both large and small salivary glands and may be considered one of the most important factors influencing the behavior of oral cavity homeostasis. Secretion of saliva plays an important role in numerous significant biological processes. Saliva facilitates chewing and bolus formation as well as performs protective functions and determines the buffering and antibacterial prosperities of the oral environment. Salivary lipids appear to be a very important component of saliva, as their qualitative and quantitative composition can be changed in various pathological states and human diseases. It has been shown that disturbances in salivary lipid homeostasis are involved in periodontal diseases as well as various systemic disorders (e.g. cystic fibrosis, diabetes and Sjögren's syndrome). However, little is known about the role and composition of salivary lipids and their interaction with other important ingredients of human saliva, including proteins, glycoproteins and salivary mucins. The purpose of this review paper is to present the latest knowledge on salivary lipids in healthy conditions and in oral and systemic diseases.

  14. Lysosomal Storage Disorders and Malignancy

    Directory of Open Access Journals (Sweden)

    Gregory M. Pastores

    2017-02-01

    Full Text Available Lysosomal storage disorders (LSDs are infrequent to rare conditions caused by mutations that lead to a disruption in the usual sequential degradation of macromolecules or their transit within the cell. Gaucher disease (GD, a lipidosis, is among the most common LSD, with an estimated incidence of 1 in 40,000 among the Caucasian, non-Jewish population. Studies have indicated an increased frequency of polyclonal and monoclonal gammopathy among patients with GD. It has been shown that two major sphingolipids that accumulate in GD, namely, β-glucosylceramide 22:0 (βGL1-22 and glucosylsphingosine (LGL1, can be recognized by a distinct subset of CD1d-restricted human and murine type II natural killer T (NKT cells. Investigations undertaken in an affected mouse model revealed βGL1-22- and LGL1-specific NKT cells were present and constitutively promoted the expression of a T-follicular helper (TFH phenotype; injection of these lipids led to downstream induction of germinal center B cells, hypergammaglobulinemia, and the production of antilipid antibodies. Subsequent studies have found clonal immunoglobulin in 33% of sporadic human monoclonal gammopathies is also specific for the lysolipids LGL1 and lysophosphatidylcholine (LPC. Furthermore, substrate reduction ameliorated GD-associated gammopathy in mice. It had been hypothesized that chronic antigenic stimulation by the abnormal lipid storage and associated immune dysregulation may be the underlying mechanism for the increased incidence of monoclonal and polyclonal gammopathies, as well as an increased incidence of multiple myeloma in patients with GD. Current observations support this proposition and illustrate the value of investigations into rare diseases, which as ‘experiments of nature’ may provide insights into conditions found in the general population that continue to remain incompletely understood.

  15. Rosemary and oxygen scavenger in active packaging for prevention of high-pressure induced lipid oxidation in pork patties

    DEFF Research Database (Denmark)

    Bolumar Garcia, Jose Tomas; Lapena Gomez, David; Skibsted, Leif Horsfelt

    2016-01-01

    Three different packaging systems: vacuum packaging, rosemary active packaging, and oxygen scavenger packaging were compared for their ability to counteract lipid oxidation in pork patties upon storage at 5 °C for 60 days following high pressure processing (HPP) (700 MPa, 10 min, 5 °C). Lipid oxi...

  16. 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 ... respond or are unable to tolerate conventional amphotericin B therapy. Amphotericin B lipid complex injection is in ...

  17. An Enhanced Platform for Bioelectrochemical Systems: A Novel Approach to Characterize Lipid Structure on Graphene

    Science.gov (United States)

    Farell, Megan; Wetherington, Maxwell; Robinson, Joshua; Kumar, Manish

    Graphene is a two-dimensional material composed of a single carbon layer that offers several appealing properties including high conductivity, large surface area, and flexibility. Its unique properties make graphene an ideal substrate for several applications, including energy storage, optical electronics, and medical devices. Functionalizing graphene with a lipid bilayer both increases its biocompatibility and provides a platform for diverse bioelectrochemical systems. However, characterization of lipids on graphene is challenging since traditional fluorescent methods for characterization of supported lipid structures are ineffective on graphene due to its highly quenching nature. Furthermore, there are multiple conflicting models published for the structure of lipids on graphene. We demonstrate that a novel technique using Raman spectroscopy and photoluminescence (PL) allows for characterization of lipids on graphene while providing additional benefits over conventional setups. We use Raman-PL in conjunction with liquid-AFM and QCM-D to determine the structure, fluidity, and homogeneity of lipids on graphene. MRI-PSIEE Grant.

  18. Small scale production and storage quality of drymilled degermed ...

    African Journals Online (AJOL)

    ... hard grains, which can be stored up to 6 months without significant deterioration. In parallel, physicochemical and rheological haracterizations showed that the main reaction occurring during storage is lipid degradation, which slightly increased fat acidity, hence decreasing taste and elasticity acceptability of the paste.

  19. Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage

    Directory of Open Access Journals (Sweden)

    Arunima Ghosh

    2012-01-01

    Full Text Available von Willebrand disease (VWD is the most common inherited human bleeding disorder and is caused by quantitative or qualitative defects in von Willebrand factor (VWF. VWF is a secreted glycoprotein that circulates as large multimers. While reduced VWF is associated with bleeding, elevations in overall level or multimer size are implicated in thrombosis. The zebrafish is a powerful genetic model in which the hemostatic system is well conserved with mammals. The ability of this organism to generate thousands of offspring and its optical transparency make it unique and complementary to mammalian models of hemostasis. Previously, partial clones of zebrafish vwf have been identified, and some functional conservation has been demonstrated. In this paper we clone the complete zebrafish vwf cDNA and show that there is conservation of domain structure. Recombinant zebrafish Vwf forms large multimers and pseudo-Weibel-Palade bodies (WPBs in cell culture. Larval expression is in the pharyngeal arches, yolk sac, and intestinal epithelium. These results provide a foundation for continued study of zebrafish Vwf that may further our understanding of the mechanisms of VWD.

  20. Caveolin-2 associates with intracellular chlamydial inclusions independently of caveolin-1

    Directory of Open Access Journals (Sweden)

    Norkin Leonard C

    2004-07-01

    Full Text Available Abstract Background Lipid raft domains form in plasma membranes of eukaryotic cells by the tight packing of glycosphingolipids and cholesterol. Caveolae are invaginated structures that form in lipid raft domains when the protein caveolin-1 is expressed. The Chlamydiaceae are obligate intracellular bacterial pathogens that replicate entirely within inclusions that develop from the phagocytic vacuoles in which they enter. We recently found that host cell caveolin-1 is associated with the intracellular vacuoles and inclusions of some chlamydial strains and species, and that entry of those strains depends on intact lipid raft domains. Caveolin-2 is another member of the caveolin family of proteins that is present in caveolae, but of unknown function. Methods We utilized a caveolin-1 negative/caveolin-2 positive FRT cell line and laser confocal immunofluorescence techniques to visualize the colocalization of caveolin-2 with the chlamydial inclusions. Results We show here that in infected HeLa cells, caveolin-2, as well as caveolin-1, colocalizes with inclusions of C. pneumoniae (Cp, C. caviae (GPIC, and C. trachomatis serovars E, F and K. In addition, caveolin-2 also associates with C. trachomatis serovars A, B and C, although caveolin-1 did not colocalize with these organisms. Moreover, caveolin-2 appears to be specifically, or indirectly, associated with the pathogens at the inclusion membranes. Using caveolin-1 deficient FRT cells, we show that although caveolin-2 normally is not transported out of the Golgi in the absence of caveolin-1, it nevertheless colocalizes with chlamydial inclusions in these cells. However, our results also show that caveolin-2 did not colocalize with UV-irradiated Chlamydia in FRT cells, suggesting that in these caveolin-1 negative cells, pathogen viability and very likely pathogen gene expression are necessary for the acquisition of caveolin-2 from the Golgi. Conclusion Caveolin-2 associates with the chlamydial

  1. Lipid classification, structures and tools☆

    OpenAIRE

    Fahy, Eoin; Cotter, Dawn; Sud, Manish; Subramaniam, Shankar

    2011-01-01

    The study of lipids has developed into a research field of increasing importance as their multiple biological roles in cell biology, physiology and pathology are becoming better understood. The Lipid Metabolites and Pathways Strategy (LIPID MAPS) consortium is actively involved in an integrated approach for the detection, quantitation and pathway reconstruction of lipids and related genes and proteins at a systems-biology level. A key component of this approach is a bioinformatics infrastruct...

  2. Motility parameters and intracellular ATP content of rabbit spermatozoa stored for 3 days at 15 degrees C.

    Science.gov (United States)

    Gogol, Piotr

    2013-01-01

    The effect of semen storage duration on motility parameters and ATP content of rabbit spermatozoa were investigated. Ejaculates were collected from 9 New Zealand White male rabbits and diluted with a commercial rabbit semen extender Galap. Semen was stored at 15 degrees C for 3 days. On each day of storage sperm motility and intracellular ATP content were evaluated. Sperm motility parameters were assessed using the computer-assisted sperm analysis (CASA) system and ATP content using the bioluminescence method. The time of storage had a significant effect on sperm motility parameters (except straight-line velocity) and ATP content. A significant correlation was observed between motility parameters and sperm ATP content. The motility parameters most strongly correlated with ATP content were total motile spermatozoa (r = 0.6364), progressively motile spermatozoa (r = 0.529), amplitude of lateral head displacement (r = 0.4178), curvilinear velocity (r = 0.4111) and average path velocity (r = 0.3743). Results show that motility parameters determined using the CASA system and intracellular ATP content are sensitive indicators of sperm quality during in vitro storage and may be useful for estimation of in vivo fertilizing ability of rabbit semen.

  3. Effect of zinc binding residues in growth hormone (GH) and altered intracellular zinc content on regulated GH secretion.

    Science.gov (United States)

    Petkovic, Vibor; Miletta, Maria Consolata; Eblé, Andrée; Iliev, Daniel I; Binder, Gerhard; Flück, Christa E; Mullis, Primus E

    2013-11-01

    Endocrine cells store hormones in concentrated forms (aggregates) in dense-core secretory granules that are released upon appropriate stimulation. Zn(2+) binding to GH through amino acid residues His18, His21, and Glu174 are essential for GH dimerization and might mediate its aggregation and storage in secretory granules. To investigate whether GH-1 gene mutations at these positions interfere with this process, GH secretion and intracellular production were analyzed in GC cells (rat pituitary cell line) transiently expressing wt-GH and/or GH Zn mutant (GH-H18A-H21A-E174A) in forskolin-stimulated vs nonstimulated conditions. Reduced secretion of the mutant variant (alone or coexpressed with wt-GH) compared with wt-GH after forskolin stimulation was observed, whereas an increased intracellular accumulation of GH Zn mutant vs wt-GH correlates with its altered extracellular secretion. Depleting Zn(2+) from culture medium using N,N,N',N'-tetrakis(2-pyridylemethyl)ethylenediamine, a high-affinity Zn(2+) chelator, led to a significant reduction of the stimulated wt-GH secretion. Furthermore, externally added Zn(2+) to culture medium increased intracellular free Zn(2+) levels and recovered wt-GH secretion, suggesting its direct dependence on free Zn(2+) levels after forskolin stimulation. Confocal microscopy analysis of the intracellular secretory pathway of wt-GH and GH Zn mutant indicated that both variants pass through the regulated secretory pathway in a similar manner. Taken together, our data support the hypothesis that loss of affinity of GH to Zn(2+) as well as altering intracellular free Zn(2+) content may interfere with normal GH dimerization (aggregation) and storage of the mutant variant (alone or with wt-GH), which could possibly explain impaired GH secretion.

  4. Optimization of input parameters of acoustic-transfection for the intracellular delivery of macromolecules using FRET-based biosensors

    Science.gov (United States)

    Yoon, Sangpil; Wang, Yingxiao; Shung, K. K.

    2016-03-01

    Acoustic-transfection technique has been developed for the first time. We have developed acoustic-transfection by integrating a high frequency ultrasonic transducer and a fluorescence microscope. High frequency ultrasound with the center frequency over 150 MHz can focus acoustic sound field into a confined area with the diameter of 10 μm or less. This focusing capability was used to perturb lipid bilayer of cell membrane to induce intracellular delivery of macromolecules. Single cell level imaging was performed to investigate the behavior of a targeted single-cell after acoustic-transfection. FRET-based Ca2+ biosensor was used to monitor intracellular concentration of Ca2+ after acoustic-transfection and the fluorescence intensity of propidium iodide (PI) was used to observe influx of PI molecules. We changed peak-to-peak voltages and pulse duration to optimize the input parameters of an acoustic pulse. Input parameters that can induce strong perturbations on cell membrane were found and size dependent intracellular delivery of macromolecules was explored. To increase the amount of delivered molecules by acoustic-transfection, we applied several acoustic pulses and the intensity of PI fluorescence increased step wise. Finally, optimized input parameters of acoustic-transfection system were used to deliver pMax-E2F1 plasmid and GFP expression 24 hours after the intracellular delivery was confirmed using HeLa cells.

  5. LMSD: LIPID MAPS structure database

    Science.gov (United States)

    Sud, Manish; Fahy, Eoin; Cotter, Dawn; Brown, Alex; Dennis, Edward A.; Glass, Christopher K.; Merrill, Alfred H.; Murphy, Robert C.; Raetz, Christian R. H.; Russell, David W.; Subramaniam, Shankar

    2007-01-01

    The LIPID MAPS Structure Database (LMSD) is a relational database encompassing structures and annotations of biologically relevant lipids. Structures of lipids in the database come from four sources: (i) LIPID MAPS Consortium's core laboratories and partners; (ii) lipids identified by LIPID MAPS experiments; (iii) computationally generated structures for appropriate lipid classes; (iv) biologically relevant lipids manually curated from LIPID BANK, LIPIDAT and other public sources. All the lipid structures in LMSD are drawn in a consistent fashion. In addition to a classification-based retrieval of lipids, users can search LMSD using either text-based or structure-based search options. The text-based search implementation supports data retrieval by any combination of these data fields: LIPID MAPS ID, systematic or common name, mass, formula, category, main class, and subclass data fields. The structure-based search, in conjunction with optional data fields, provides the capability to perform a substructure search or exact match for the structure drawn by the user. Search results, in addition to structure and annotations, also include relevant links to external databases. The LMSD is publicly available at PMID:17098933

  6. Intracellular Shuttle: The Lactate Aerobic Metabolism

    Directory of Open Access Journals (Sweden)

    Rogério Santos de Oliveira Cruz

    2012-01-01

    Full Text Available Lactate is a highly dynamic metabolite that can be used as a fuel by several cells of the human body, particularly during physical exercise. Traditionally, it has been believed that the first step of lactate oxidation occurs in cytosol; however, this idea was recently challenged. A new hypothesis has been presented based on the fact that lactate-to-pyruvate conversion cannot occur in cytosol, because the LDH enzyme characteristics and cytosolic environment do not allow the reaction in this way. Instead, the Intracellular Lactate Shuttle hypothesis states that lactate first enters in mitochondria and only then is metabolized. In several tissues of the human body this idea is well accepted but is quite resistant in skeletal muscle. In this paper, we will present not only the studies which are protagonists in this discussion, but the potential mechanism by which this oxidation occurs and also a link between lactate and mitochondrial proliferation. This new perspective brings some implications and comes to change our understanding of the interaction between the energy systems, because the product of one serves as a substrate for the other.

  7. An intracellular anion channel critical for pigmentation

    Science.gov (United States)

    Bellono, Nicholas W; Escobar, Iliana E; Lefkovith, Ariel J; Marks, Michael S; Oancea, Elena

    2014-01-01

    Intracellular ion channels are essential regulators of organellar and cellular function, yet the molecular identity and physiological role of many of these channels remains elusive. In particular, no ion channel has been characterized in melanosomes, organelles that produce and store the major mammalian pigment melanin. Defects in melanosome function cause albinism, characterized by vision and pigmentation deficits, impaired retinal development, and increased susceptibility to skin and eye cancers. The most common form of albinism is caused by mutations in oculocutaneous albinism II (OCA2), a melanosome-specific transmembrane protein with unknown function. Here we used direct patch-clamp of skin and eye melanosomes to identify a novel chloride-selective anion conductance mediated by OCA2 and required for melanin production. Expression of OCA2 increases organelle pH, suggesting that the chloride channel might regulate melanin synthesis by modulating melanosome pH. Thus, a melanosomal anion channel that requires OCA2 is essential for skin and eye pigmentation. DOI: http://dx.doi.org/10.7554/eLife.04543.001 PMID:25513726

  8. Intracellular recording from a spider vibration receptor.

    Science.gov (United States)

    Gingl, Ewald; Burger, Anna-M; Barth, Friedrich G

    2006-05-01

    The present study introduces a new preparation of a spider vibration receptor that allows intracellular recording of responses to natural mechanical or electrical stimulation of the associated mechanoreceptor cells. The spider vibration receptor is a lyriform slit sense organ made up of 21 cuticular slits located on the distal end of the metatarsus of each walking leg. The organ is stimulated when the tarsus receives substrate vibrations, which it transmits to the organ's cuticular structures, reducing the displacement to about one tenth due to geometrical reasons. Current clamp recording was used to record action potentials generated by electrical or mechanical stimuli. Square pulse stimulation identified two groups of sensory cells, the first being single-spike cells which generated only one or two action potentials and the second being multi-spike cells which produced bursts of action potentials. When the more natural mechanical sinusoidal stimulation was applied, differences in adaptation rate between the two cell types remained. In agreement with prior extracellular recordings, both cell types showed a decrease in the threshold tarsus deflection with increasing stimulus frequency. Off-responses to mechanical stimuli have also been seen in the metatarsal organ for the first time.

  9. On the Computing Potential of Intracellular Vesicles.

    Science.gov (United States)

    Mayne, Richard; Adamatzky, Andrew

    2015-01-01

    Collision-based computing (CBC) is a form of unconventional computing in which travelling localisations represent data and conditional routing of signals determines the output state; collisions between localisations represent logical operations. We investigated patterns of Ca2+-containing vesicle distribution within a live organism, slime mould Physarum polycephalum, with confocal microscopy and observed them colliding regularly. Vesicles travel down cytoskeletal 'circuitry' and their collisions may result in reflection, fusion or annihilation. We demonstrate through experimental observations that naturally-occurring vesicle dynamics may be characterised as a computationally-universal set of Boolean logical operations and present a 'vesicle modification' of the archetypal CBC 'billiard ball model' of computation. We proceed to discuss the viability of intracellular vesicles as an unconventional computing substrate in which we delineate practical considerations for reliable vesicle 'programming' in both in vivo and in vitro vesicle computing architectures and present optimised designs for both single logical gates and combinatorial logic circuits based on cytoskeletal network conformations. The results presented here demonstrate the first characterisation of intracelluar phenomena as collision-based computing and hence the viability of biological substrates for computing.

  10. The effects of gamma radiation on fish lipids

    International Nuclear Information System (INIS)

    Sofyan, Rochestri

    1982-01-01

    Investigations on the changes of free fatty acid (FFA) value and thiobarbituric acid (TBA) value of fish muscle lipids during chilled storage were carried out. Experimental results showed significant increases in FFA and TBA values during storage. The FFA and TBA values of unirradiated fish were also determined. It was observed that radiation treatments at doses of 2.5 and 5.0 kGy gave no significant effects on FFA values. On the other hand the TBA values of irradiated samples were significantly higher than those of unirradiated samples, indicating that oxidative changes have occured due to radiation. TLC investigations on muscle nonpolar-, phospho- and glycolipids of control and fish samples, irradiated at doses up to 10 kGy revealed that the lipid components or irradiated fish were identical with those of control. (author)

  11. Storage in Europe

    International Nuclear Information System (INIS)

    Cabanes, J.M.; Rottenberg, J.; Abiad, A.; Caudron, S.; Girault, Ph.

    2007-01-01

    Storage represents one of the key elements among the different modulation tools. How the problem of storage is put forward in Europe in front of the increasing uncertainty of the gas demand and prices? What are the policies implemented by storage facility operators? To what extend storage can amortize gas prices volatility or allow the market actors to take the best profit of this volatility? These are the questions debated at this workshop by four specialists of this domain. (J.S.)

  12. Abstract Storage Devices

    OpenAIRE

    Koenig, Robert; Maurer, Ueli; Tessaro, Stefano

    2007-01-01

    A quantum storage device differs radically from a conventional physical storage device. Its state can be set to any value in a certain (infinite) state space, but in general every possible read operation yields only partial information about the stored state. The purpose of this paper is to initiate the study of a combinatorial abstraction, called abstract storage device (ASD), which models deterministic storage devices with the property that only partial information about the state can be re...

  13. Heat transport and storage

    International Nuclear Information System (INIS)

    Despois, J.

    1977-01-01

    Recalling the close connections existing between heat transport and storage, some general considerations on the problem of heat distribution and transport are presented 'in order to set out the problem' of storage in concrete form. This problem is considered in its overall plane, then studied under the angle of the different technical choices it involves. The two alternatives currently in consideration are described i.e.: storage in a mined cavity and underground storage as captive sheet [fr

  14. Fuel assembly storage pool

    International Nuclear Information System (INIS)

    Hiranuma, Hiroshi.

    1976-01-01

    Object: To remove limitation of the number of storage of fuel assemblies to increase the number of storage thereof so as to relatively reduce the water depth required for shielding radioactive rays. Structure: Fuel assembly storage rack containers for receiving a plurality of spent fuel assembly racks are stacked in multi-layer fashion within a storage pool filled with water for shielding radioactive rays and removing heat. (Furukawa, Y.)

  15. Fuel storage systems

    Energy Technology Data Exchange (ETDEWEB)

    Donakowski, T.D.; Tison, R.R.

    1979-08-01

    Storage technologies are characterized for solid, liquid, and gaseous fuels. Emphasis is placed on storage methods applicable to Integrated Community Energy Systems based on coal. Items discussed here include standard practice, materials and energy losses, environmental effects, operating requirements, maintenance and reliability, and cost considerations. All storage systems were found to be well-developed and to represent mature technologies; an exception may exist for low-Btu gas storage, which could have materials incompatability.

  16. Modeling HIV-1 intracellular replication: two simulation approaches

    NARCIS (Netherlands)

    Zarrabi, N.; Mancini, E.; Tay, J.; Shahand, S.; Sloot, P.M.A.

    2010-01-01

    Many mathematical and computational models have been developed to investigate the complexity of HIV dynamics, immune response and drug therapy. However, there are not many models which consider the dynamics of virus intracellular replication at a single level. We propose a model of HIV intracellular

  17. Pico gauges for minimally invasive intracellular hydrostatic pressure measurements

    DEFF Research Database (Denmark)

    Knoblauch, Jan; Mullendore, Daniel L.; Jensen, Kaare Hartvig

    2014-01-01

    Intracellular pressure has a multitude of functions in cells surrounded by a cell wall or similar matrix in all kingdoms of life. The functions include cell growth, nastic movements, and penetration of tissue by parasites. The precise measurement of intracellular pressure in the majority of cells...

  18. Intracellular angiotensin II inhibits heterologous receptor stimulated Ca2+ entry

    NARCIS (Netherlands)

    Filipeanu, CM; Brailoiu, E; Henning, RH; Deelman, LE; de Zeeuw, D; Nelemans, SA

    2001-01-01

    Recent studies show that angiotensin II (AngII) can act from within the cell, possibly via intracellular receptors pharmacologically different from typical plasma membrane AngII receptors. The role of this intracellular AngII (AngII(i)) is unclear. Besides direct effects of AngII(i) on cellular

  19. Development of bacterial cell-based system for intracellular ...

    African Journals Online (AJOL)

    Development of bacterial cell-based system for intracellular antioxidant activity screening assay using green fluorescence protein (GFP) reporter. ... Both strains demonstrated that quercetin and α- tocopherol exhibited the most potent and significant antioxidant activity with more than 60% reduction of intracellular superoxide ...

  20. Wrinkled1 accelerates flowering and regulates lipid homeostasis between oil accumulation and membrane lipid anabolism in Brassica napus

    Directory of Open Access Journals (Sweden)

    Qing eLi

    2015-11-01

    Full Text Available Wrinkled1 (WRI1 belongs to the APETALA2 transcription factor family; it is unique to plants and is a central regulator of oil synthesis in Arabidopsis. The effects of WRI1 on comprehensive lipid metabolism and plant development were unknown, especially in crop plants. This study found that BnWRI1 in Brassica napus accelerated flowering and enhanced oil accumulation in both seeds and leaves without leading to a visible growth inhibition. BnWRI1 decreased storage carbohydrates and increased soluble sugars to facilitate the carbon flux to lipid anabolism. BnWRI1 is localized to the nucleus and directly binds to the AW-box at proximal upstream regions of genes involved in fatty acid synthesis and lipid assembly. The overexpression (OE of BnWRI1 resulted in the up-regulation of genes involved in glycolysis, fatty acid synthesis, lipid assembly, and flowering. Lipid profiling revealed increased galactolipid monogalactosyldiacylglycerol (MGDG, digalactosyldiacylglycerol (DGDG, and phosphatidylcholine (PC in the leaves of OE plants, whereas it exhibited a reduced level of the galactolipids DGDG and MGDG and increased levels of PC, phosphatidylethanolamide (PE, and oil (triacylglycerol, TAG in the siliques of OE plants during the early seed development stage. These results suggest that BnWRI1 is important for homeostasis among TAG, membrane lipids and sugars, and thus facilitates flowering and oil accumulation in B. napus.