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Lipid transport

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https://www.readbyqxmd.com/read/28433003/the-plastid-outer-membrane-localized-lptd1-is-important-for-glycerolipid-remodeling-under-phosphate-starvation
#1
Yi-Ching Hsueh, Christian Ehmann, Nadine Flinner, Roman Ladig, Enrico Schleiff
Glycerolipid synthesis in plants is coordinated between plastids and the endoplasmic reticulum (ER). A central step within the glycerolipid synthesis is the transport of phosphatidic acid from ER to chloroplasts. The chloroplast outer envelope protein TGD4 belongs to the LptD family conserved in bacteria and plants and selectively binds and may transports phosphatidic acid. We describe a second LptD-family protein in A. thaliana (atLPTD1; At2g44640) characterized by a barrel domain with an amino acid signature typical for cyanobacterial LptDs...
April 22, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28432921/gates-for-soluble-and-membrane-proteins-and-two-trafficking-systems-ift-and-lift-establish-a-dynamic-ciliary-signaling-compartment
#2
REVIEW
Victor L Jensen, Michel R Leroux
Primary cilia are microtubule-based organelles found on most mammalian cell surfaces. They possess a soluble matrix and membrane contiguous with the cell body cytosol and plasma membrane, and yet, have distinct compositions that can be modulated to enable dynamic signal transduction. Here, we discuss how specialized ciliary compartments are established using a coordinated network of gating, trafficking and targeting activities. Cilium homeostasis is maintained by a size-selective molecular mesh that limits soluble protein entry, and by a membrane diffusion barrier localized at the transition zone...
April 19, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28432465/ppar%C3%AE-activation-regulates-lipid-droplet-formation-and-lactate-production-in-rat-sertoli-cells
#3
A Gorga, G M Rindone, M Regueira, E H Pellizzari, M C Camberos, S B Cigorraga, M F Riera, M N Galardo, S B Meroni
Sertoli cells provide the structural and nutritional support for germ cell development; they actively metabolize glucose and convert it to lactate, which is an important source of energy for germ cells. Furthermore, Sertoli cells can oxidize fatty acids, a metabolic process that is assumed to fulfill their own energy requirements. Fatty acids are stored as triacylglycerides within lipid droplets. The regulation of fatty acid storage in conjunction with the regulation of lactate production may thus be relevant to seminiferous tubule physiology...
April 21, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28432377/emerging-roles-of-calpain-proteolytic-systems-in-macrophage-cholesterol-handling
#4
REVIEW
Takuro Miyazaki, Akira Miyazaki
Calpains are Ca(2+)-dependent intracellular proteases that play central roles in the post-translational processing of functional proteins. In mammals, calpain proteolytic systems comprise the endogenous inhibitor calpastatin as well as 15 homologues of the catalytic subunits and two homologues of the regulatory subunits. Recent pharmacological and gene targeting studies in experimental animal models have revealed the contribution of conventional calpains, which consist of the calpain-1 and -2 isozymes, to atherosclerotic diseases...
April 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28432031/membrane-lipid-replacement-for-chronic-illnesses-aging-and-cancer-using-oral-glycerolphospholipid-formulations-with-fructooligosaccharides-to-restore-phospholipid-function-in-cellular-membranes-organelles-cells-and-tissues
#5
REVIEW
Garth L Nicolson, Michael E Ash
Membrane Lipid Replacement is the use of functional, oral supplements containing mixtures of cell membrane glycerolphospholipids, plus fructooligosaccharides (for protection against oxidative, bile acid and enzymatic damage) and antioxidants, in order to safely replace damaged, oxidized, membrane phospholipids and restore membrane, organelle, cellular and organ function. Defects in cellular and intracellular membranes are characteristic of all chronic medical conditions, including cancer, and normal processes, such as aging...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28431663/effects-of-torcetrapib-and-statin-treatment-on-apoc-iii-and-apoprotein-defined-lipoprotein-subclasses-from-the-illuminate-trial
#6
John Bagdade, Philip Barter, Carmen Quiroga, Pierre Alaupovic
In the ILLUMINATE Trial, treatment with the cholesteryl ester transfer protein inhibitor torcetrapib resulted in a significant increase in both atherosclerotic cardiovascular disease events and total mortality which was not explained by changes in the routinely measured plasma lipids. To determine whether alterations in lipoproteins defined by their apoprotein content that are not estimated with conventional laboratory methods contributed to these unexpected events, we measured the apoB- and apoA-containing subclasses in a subgroup of ILLUMINATE participants...
March 18, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28430192/a-monodisperse-transmembrane-%C3%AE-helical-peptide-barrel
#7
Kozhinjampara R Mahendran, Ai Niitsu, Lingbing Kong, Andrew R Thomson, Richard B Sessions, Derek N Woolfson, Hagan Bayley
The fabrication of monodisperse transmembrane barrels formed from short synthetic peptides has not been demonstrated previously. This is in part because of the complexity of the interactions between peptides and lipids within the hydrophobic environment of a membrane. Here we report the formation of a transmembrane pore through the self-assembly of 35 amino acid α-helical peptides. The design of the peptides is based on the C-terminal D4 domain of the Escherichia coli polysaccharide transporter Wza. By using single-channel current recording, we define discrete assembly intermediates and show that the pore is most probably a helix barrel that contains eight D4 peptides arranged in parallel...
May 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28429758/intracellular-lipid-binding-protein-family-diversity-from-oyster-crassostrea-gigas-genomic-and-structural-features-of-invertebrate-lipid-transporters
#8
Guilherme de Toledo-Silva, Guilherme Razzera, Flavia Lucena Zacchi, Nestor Cubas Wendt, Jacó Joaquim Mattos, Afonso Celso Dias Bainy
Intracellular lipid binding proteins (iLBPs) play a role in the transport and cellular uptake of fatty acids and gene expression regulation. The aim of this work was to characterize the iLBP gene family of the Pacific oyster Crassostrea gigas, one of the most cultivated marine bivalves in the world, using bioinformatics and molecular biology approaches. A total of 26 different iLBPs transcripts were identified in the Pacific oyster genome, including alternative splicing and gene duplication events. The oyster iLBP gene family seems to be more expanded than in other invertebrates...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428821/genome-wide-search-for-candidate-genes-for-yeast-robustness-improvement-against-formic-acid-reveals-novel-susceptibility-trk1-and-positive-regulators-and-resistance-haa1-regulon-determinants
#9
Sílvia F Henriques, Nuno P Mira, Isabel Sá-Correia
BACKGROUND: Formic acid is an inhibitory compound present in lignocellulosic hydrolysates. Understanding the complex molecular mechanisms underlying Saccharomyces cerevisiae tolerance to this weak acid at the system level is instrumental to guide synthetic pathway engineering for robustness improvement of industrial strains envisaging their use in lignocellulosic biorefineries. RESULTS: This study was performed to identify, at a genome-wide scale, genes whose expression confers protection or susceptibility to formic acid, based on the screening of a haploid deletion mutant collection to search for these phenotypes in the presence of 60, 70 and 80 mM of this acid, at pH 4...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28428350/targeted-inactivation-of-copper-transporter-atp7b-in-hepatocytes-causes-liver-steatosis-and-obesity-in-mice
#10
Abigael Muchenditsi, Haojun Yang, James P Hamilton, Lahari Koganti, Franck Housseau, Lisa Aronov, Hongni Fan, Hannah Pierson, Ashima Bhattacharjee, Robert C Murphy, Cynthia L Sears, James J Potter, Clavia Ruth Wooton-Kee, Svetlana Lutsenko
The copper transporter ATP7B is essential for mammalian copper homeostasis. Mutations in ATP7B result in copper accumulation, especially in the liver, and cause Wilson disease (WD). The major role of hepatocytes in WD pathology is firmly established. It is less certain whether the excess Cu in hepatocytes is solely responsible for development of WD. To address this issue, we generated a mouse strain for Cre-mediated deletion of Atp7b and inactivated Atp7b selectively in hepatocytes. Atp7bΔ(Hep) mice accumulate copper in the liver, have elevated urinary copper, lack holo-ceruloplasmin, but show no liver disease for up to 30 weeks...
April 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28428331/a-personalized-model-of-coq2-nephropathy-rescued-by-the-wild-type-coq2-allele-or-dietary-coenzyme-q10-supplementation
#11
Jun-Yi Zhu, Yulong Fu, Adam Richman, Zhanzheng Zhao, Patricio E Ray, Zhe Han
Clinical studies have identified patients with nephrotic syndrome caused by mutations in genes involved in the biosynthesis of coenzyme Q10 (CoQ10), a lipid component of the mitochondrial electron transport chain and an important antioxidant. However, the cellular mechanisms through which these mutations induce podocyte injury remain obscure. Here, we exploited the striking similarities between Drosophila nephrocytes and human podocytes to develop a Drosophila model of these renal diseases, and performed a systematic in vivo analysis assessing the role of CoQ10 pathway genes in renal function...
April 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28428217/microrna-33-regulates-macrophage-autophagy-in-atherosclerosis
#12
Mireille Ouimet, Hasini Ediriweera, Milessa Silva Afonso, Bhama Ramkhelawon, Ragunath Singaravelu, Xianghai Liao, Rachel C Bandler, Karishma Rahman, Edward A Fisher, Katey J Rayner, John P Pezacki, Ira Tabas, Kathryn J Moore
OBJECTIVE: Defective autophagy in macrophages leads to pathological processes that contribute to atherosclerosis, including impaired cholesterol metabolism and defective efferocytosis. Autophagy promotes the degradation of cytoplasmic components in lysosomes and plays a key role in the catabolism of stored lipids to maintain cellular homeostasis. microRNA-33 (miR-33) is a post-transcriptional regulator of genes involved in cholesterol homeostasis, yet the complete mechanisms by which miR-33 controls lipid metabolism are unknown...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28426163/lipid-flip-flop-and-pore-nucleation-on-zwitterionic-bilayers-are-asymmetric-under-ionic-imbalance
#13
Jiaqi Lin, Roozbeh Dargazany, Alfredo Alexander-Katz
Lipid flip-flop and its associated transient pore formation are key thermodynamic properties of living cell membranes. However, there is a lack of understanding of whether ionic imbalance that exists ubiquitously across cell membranes affects lipid flip-flop and its associated functions. Potential of mean force calculations show that the free-energy barrier of lipid flip-flop on the extracellular leaflet reduces with the presence of ionic imbalance, whereas the barrier on the intracellular leaflet is generally not affected...
April 20, 2017: Small
https://www.readbyqxmd.com/read/28424539/%C3%AE-3-adrenoceptor-activation-upregulates-apolipoprotein-a-i-expression-in-hepg2-cells-which-might-further-promote-cholesterol-efflux-from-macrophage-foam-cells
#14
Xia-Qing Gao, Yan-Fang Li, Zhi-Li Jiang
OBJECTIVE: The aim of this study was to explore the effects of β3-adrenoceptor (β3-AR) activation on HepG2 cells and its influence on cholesterol efflux from macrophage foam cells. MATERIALS AND METHODS: HepG2 cells were cultured and treated with the β3-AR agonist, BRL37344, and antagonist, SR52390A, and the expression of apolipoprotein (Apo) A-I, ApoA-II, ApoB, and β3-AR in the supernatants and cells was determined. The expression of peroxisome proliferator-activated receptor (PPAR) γ and PPARα in the HepG2 cells was also assessed...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28424515/structure-and-allosteric-inhibition-of-excitatory-amino-acid-transporter-1
#15
Juan C Canul-Tec, Reda Assal, Erica Cirri, Pierre Legrand, Sébastien Brier, Julia Chamot-Rooke, Nicolas Reyes
Human members of the solute carrier 1 (SLC1) family of transporters take up excitatory neurotransmitters in the brain and amino acids in peripheral organs. Dysregulation of the function of SLC1 transporters is associated with neurodegenerative disorders and cancer. Here we present crystal structures of a thermostabilized human SLC1 transporter, the excitatory amino acid transporter 1 (EAAT1), with and without allosteric and competitive inhibitors bound. The structures reveal architectural features of the human transporters, such as intra- and extracellular domains that have potential roles in transport function, regulation by lipids and post-translational modifications...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28423959/diabetic-pregnancy-maternal-and-fetal-docosahexaenoic-acid-a-review-of-existing-evidence
#16
Pauline Léveillé, Clémence Rouxel, Mélanie Plourde
OBJECTIVE: Docosahexaenoic acid (DHA) is vital for fetal development especially during the third trimester of gestation when the speed of fetal brain growth is at its peak. Diabetes modifies the maternal fatty acid profile, which may in turn change the quantity and/or quality of lipids transferred to the fetus. Neonates born to diabetic mothers might be more vulnerable to DHA deficiency leading to lower cognitive scores together with lower overall intellectual quotients when compared to control...
April 19, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28422165/structural-basis-of-inhibition-of-lipid-linked-oligosaccharide-flippase-pglk-by-a-conformational-nanobody
#17
Camilo Perez, Martin Köhler, Daniel Janser, Els Pardon, Jan Steyaert, Renato Zenobi, Kaspar P Locher
PglK is an ABC transporter that flips a lipid-linked oligosaccharide (LLO) that serves as a donor in protein N-glycosylation. Previous structures revealed two inward-facing conformations, both with very large separations of the nucleotide binding domains (NBDs), and a closed, ADP-bound state that featured an occluded cavity. To investigate additional states, we developed conformation-sensitive, single-domain camelid nanobodies (Nb) and studied their effect on PglK activity. Biochemical, structural, and mass spectrometric analyses revealed that one inhibitory Nb binds as a single copy to homodimeric PglK...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28421422/hepatitis-c-virus-genotype-3-update-on-current-and-emergent-therapeutic-interventions
#18
REVIEW
Steven W Johnson, Dorothea K Thompson, Brianne Raccor
PURPOSE OF REVIEW: Direct-acting antiviral agents (DAAs) have markedly improved the prognosis of hepatitis C virus (HCV)-genotype 3 (GT3), a highly prevalent infection worldwide. However, in patients with hepatic fibrosis, cirrhosis, or hepatocellular carcinoma (HCC), GT3 infection presents a treatment challenge compared with other genotypes. The dependence of the HCV life cycle on host lipid metabolism suggests the possible utility of targeting host cellular factors for combination anti-HCV therapy...
June 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28421113/chronic-hyperinsulinaemic-hypoglycaemia-in-rats-is-accompanied-by-increased-body-weight-hyperleptinaemia-and-decreased-neuronal-glucose-transporter-levels-in-the-brain
#19
Vivi F H Jensen, Anne-Marie Mølck, Melissa Chapman, Lene Alifrangis, Lene Andersen, Jens Lykkesfeldt, Ingrid B Bøgh
The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28421043/outlining-core-pathways-of-amyloid-toxicity-in-bacteria-with-the-repa-wh1-prionoid
#20
Laura Molina-García, María Moreno-Del Álamo, Pedro Botias, Zaira Martín-Moldes, María Fernández, Alicia Sánchez-Gorostiaga, Aída Alonso-Del Valle, Juan Nogales, Jesús García-Cantalejo, Rafael Giraldo
The synthetic bacterial prionoid RepA-WH1 causes a vertically transmissible amyloid proteinopathy in Escherichia coli that inhibits growth and eventually kills the cells. Recent in vitro studies show that RepA-WH1 builds pores through model lipid membranes, suggesting a possible mechanism for bacterial cell death. By comparing acutely (A31V) and mildly (ΔN37) cytotoxic mutant variants of the protein, we report here that RepA-WH1(A31V) expression decreases the intracellular osmotic pressure and compromise bacterial viability under either aerobic or anaerobic conditions...
2017: Frontiers in Microbiology
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