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Phosphatidic acid

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https://www.readbyqxmd.com/read/28326614/recombinant-expression-of-porcine-spermadhesin-awn-and-its-phospholipid-interaction-indication-for-a-novel-lipid-binding-property
#1
F Schröter, K Müller, P Müller, E Krause, B C Braun
AWN is a porcine (Sus scrofa domestica) seminal plasma protein and has been linked to a variety of processes related to fertilization. To acquire the protein in sufficient amount and purity for functional studies, we established its recombinant expression in E. coli and a three-step purification protocol based on different chromatographies. The test for AWN-phospholipid interaction revealed phosphatidic acid and cardiolipin as potential binding partners. As phosphatidic acid is surmised to play a role in cation-induced membrane destabilization and fusion events, we propose a membrane protective function of the presented binding affinity...
March 21, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28323521/hs1bp3-provides-a-novel-mechanism-of-negative-autophagy-regulation-through-membrane-lipids
#2
Zhangyuan Yin, Daniel J Klionsky
The formation and maturation of the autophagosome, a morphological hallmark of macroautophagy/autophagy, is tightly controlled with regard to location, timing and intensity. Various proteins have been characterized to be essential in regulating autophagosome biogenesis, whereas little is known about the roles of specific lipids and their metabolizing enzymes in this process. In a recent paper, Holland et al. identified the phosphoinositide-binding protein HS1BP3 as a novel negative regulator of autophagosome formation...
March 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28322795/a-comprehensive-lipid-binding-and-activity-validation-of-a-cancer-specific-peptide-peptoid-hybrid-pps1
#3
Tanvi J Desai, D Gomika Udugamasooriya
We recently identified a peptide-peptoid hybrid, PPS1, which recognizes lipids that have an overall negative charge, such as phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidic acid (PA), and phosphatidylinositol (PI), but that does not bind to neutral lipids, such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), and sphingomyelin (SM). The simple dimeric version of PPS1, PPS1D1, displayed strong cytotoxicity to cancer cells over normal cells in vitro and tumor burden in vivo. In this study, we comprehensively characterized the direct binding and activity of PPS1 on PS, PG, and PA using liposome-based assays and lung cancer cell lines that express these negatively charged lipids...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28318354/hs1bp3-inhibits-autophagy-by-regulation-of-pld1
#4
Kristiane Søreng, Helene Knævelsrud, Petter Holland, Anne Simonsen
Macroautophagy/autophagy is a membrane trafficking and intracellular degradation process involving the formation of double-membrane autophagosomes and their ultimate fusion with lysosomes. Much is yet to be learned about the regulation of this process, especially at the level of the membranes and lipids involved. We have recently found that the PX domain protein HS1BP3 (HCLS1 binding protein 3) is a negative regulator of autophagosome formation. HS1BP3 depletion increases the formation of LC3-positive autophagosomes both in human cells and zebrafish...
February 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28303896/phospholipid-imprinted-polymers-as-selective-endotoxin-scavengers
#5
Robert Sulc, Gyorgy Szekely, Sudhirkumar Shinde, Celina Wierzbicka, Filipe Vilela, David Bauer, Börje Sellergren
Herein we explore phospholipid imprinting as a means to design receptors for complex glycolipids comprising the toxic lipopolysaccharide endotoxin. A series of polymerizable bis-imidazolium and urea hosts were evaluated as cationic and neutral hosts for phosphates and phosphonates, the latter used as mimics of the phospholipid head groups. The bis-imidazolium hosts interacted with the guests in a cooperative manner leading to the presence of tight and well defined 1:2 ternary complexes. Optimized monomer combinations were subsequently used for imprinting of phosphatidic acid as an endotoxin dummy template...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28276191/deleting-the-dag-kinase-dgk1-augments-yeast-vacuole-fusion-through-increased-ypt7-activity-and-altered-membrane-fluidity
#6
Gregory E Miner, Matthew L Starr, Logan R Hurst, Rutilio A Fratti
Diacylglycerol (DAG) is a fusogenic lipid that can be produced through phospholipase C activity on phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2 ], or through phosphatidic acid (PA) phosphatase activity. The fusion of Saccharomyces cerevisiae vacuoles requires DAG, PA and PI(4,5)P2 , and the production of these lipids is thought to provide temporally specific stoichiometries that are critical for each stage of fusion. Furthermore, DAG and PA can be interconverted by the DAG kinase Dgk1 and the PA phosphatase Pah1...
March 9, 2017: Traffic
https://www.readbyqxmd.com/read/28264934/structure-activity-relationship-of-thapsigargin-inhibition-on-the-purified-golgi-secretory-pathway-ca2-mn2-transport-atpase-spca1a
#7
Jialin Chen, Joren De Raeymaecker, Jannik Brøndsted Hovgaard, Susanne Smaardijk, Ilse Vandecaetsbeek, Frank Wuytack, Jesper Vuust Møller, Jan Eggermont, Marc De Maeyer, Søren Brøgger Christensen, Peter Vangheluwe
The Golgi/secretory pathway Ca2+/Mn2+ transport ATPase (SPCA1a) is implicated in breast cancer and Hailey-Hailey disease. Here, we purified recombinant human SPCA1a from Saccharomyces cerevisiae and measured Ca2+ dependent ATPase activity following reconstitution in proteoliposomes. The purified SPCA1a displays a higher apparent Ca2+ affinity and lower maximal turnover rate than the purified sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1a). The lipids cholesteryl hemisuccinate, linole-/oleamide and phosphatidyl ethanolamine inhibit, whereas phosphatidic acid and sphingomyelin enhance SPCA1a activity...
March 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28260060/bioinformatics-analysis-on-the-differentiation-of-bone-mesenchymal-stem-cells-into-osteoblasts-and-adipocytes
#8
Xiaoyuan Xu, He Jiang, Xingnuan Li, Ping Wu, Jianyun Liu, Tao Wang, Xiaoou Zhou, Jianjun Xiong, Weidong Li
The present study aimed to screen several differentially expressed genes (DEGs) and differentially expressed microRNAs (miRNAs) for two types of mesenchymal stem cell (MSC) differentiation. Bone morphogenetic protein 6 (BMP‑6) and dexamethasone were used to induce MSCs towards osteoblastic differentiation or adipocytic differentiation. The t‑test in the Bioconductor bioinformatics software tool was used to screen DEGs and differentially expressed miRNAs in the two samples. Subsequent gene ontology (GO) and pathway analyses on the DEGs were performed using the GO and Kyoto Encyclopedia of Genes and Genomes databases, respectively; potential target genes for the screened miRNAs were predicted using the TargetScan database...
February 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28246337/diacylglycerol-kinase-%C3%AF%C2%B5-deficiency-preserves-glucose-tolerance-and-modulates-lipid-metabolism-in-obese-mice
#9
Louise Mannerås-Holm, Milena Schönke, Joseph T Brozinick, Laurène Vetterli, Hai-Hoang Bui, Philip Sanders, Emmani B M Nascimento, Marie Björnholm, Alexander V Chibalin, Juleen R Zierath
Diacylglycerol kinases (DGKs) catalyze the phosphorylation and conversion of DAG into phosphatidic acid. DGK isozymes have unique primary structures, expression patterns, subcellular localizations, regulatory mechanisms and DAG preferences. DGKε has a hydrophobic segment that promotes its attachment to membranes and shows substrate specificity for DAG with an arachidonoyl acyl chain in the sn-2 position of the substrate. We determined the role of DGKε in the regulation of energy and glucose homeostasis in relation to diet-induced insulin resistance and obesity using DGKε deficient (KO) and wild-type mice...
February 28, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28238790/multifunctional-liposomes-interact-with-abeta-in-human-biological-fluids-therapeutic-implications-for-alzheimer-s-disease
#10
Elisa Conti, Maria Gregori, Isabella Radice, Fulvio Da Re, Denise Grana, Francesca Re, Elisa Salvati, Massimo Masserini, Carlo Ferrarese, Chiara Paola Zoia, Lucio Tremolizzo
The accumulation of extracellular amyloid beta (Abeta42) both in brain and in cerebral vessels characterizes Alzheimer's disease (AD) pathogenesis. Recently, the possibility to functionalize nanoparticles (NPs) surface with Abeta42 binding molecules, making them suitable tools for reducing Abeta42 burden has been shown effective in models of AD. Aim of this work consisted in proving that NPs might be effective in sequestering Abeta42 in biological fluids, such as CSF and plasma. This demonstration is extremely important considering that these Abeta42 pools are in continuum with the brain parenchyma with drainage of Abeta from interstitial brain tissue to blood vessel and plasma...
February 23, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28238261/lipidomic-evaluation-of-aryl-hydrocarbon-receptor-mediated-hepatic-steatosis-in-male-and-female-mice-elicited-by-2-3-7-8-tetrachlorodibenzo-p-dioxin
#11
Rance Nault, Kelly A Fader, Todd A Lydic, Timothy R Zacharewski
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces hepatic steatosis mediated by the aryl hydrocarbon receptor. To further characterize TCDD-elicited hepatic lipid accumulation, mice were gavaged with TCDD every 4 days for 28 days. Liver samples were examined using untargeted lipidomics with structural confirmation of lipid species by targeted high-resolution MS/MS, and data were integrated with complementary RNA-Seq analyses. Approximately 936 unique spectral features were detected, of which 379 were confirmed as unique lipid species...
March 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28235468/lipid-mapping-of-the-rat-brain-for-models-of-disease
#12
J Martínez-Gardeazabal, E González de San Román, M Moreno-Rodríguez, A Llorente-Ovejero, I Manuel, R Rodríguez-Puertas
Lipids not only constitute the primary component of cellular membranes and contribute to metabolism but also serve as intracellular signaling molecules and bind to specific membrane receptors to control cell proliferation, growth and convey neuroprotection. Over the last several decades, the development of new analytical techniques, such as imaging mass spectrometry (IMS), has contributed to our understanding of their involvement in physiological and pathological conditions. IMS allows researchers to obtain a wide range of information about the spatial distribution and abundance of the different lipid molecules that is crucial to understand brain functions...
February 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28229303/phospholipase-d1-expression-analysis-in-relapsing-remitting-multiple-sclerosis-patients
#13
Mohammad Mahdi Eftekharian, Tahereh Azimi, Soudeh Ghafouri-Fard, Arezou Sayad, Mir Davood Omrani, Shaghayegh Sarrafzadeh, Roghayeh Abbasalipourkabir, Mehrdokht Mazdeh, Mohammad Taheri
Multiple sclerosis (MS) is a chronic disorder resulting from destruction of the myelin or insulating covers of neurons in the central nervous system (CNS). Several lines of evidence suggest a role for immune response in the occurrence and progression of this disorder. Several disease-modifying agents (DMA) including β-interferons (IFNβ) are being used in MS patients in order to stop the disease at the early inflammatory stage, postpone disease progression and diminish future disability. Phospholipase D1 (PLD1) is a critical enzyme responsible for the making lipid second messenger phosphatidic acid...
February 22, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28223993/diacylglycerol-kinases-are-widespread-in-higher-plants-and-display-inducible-gene-expression-in-response-to-beneficial-elements-metal-and-metalloid-ions
#14
Hugo F Escobar-Sepúlveda, Libia I Trejo-Téllez, Paulino Pérez-Rodríguez, Juan V Hidalgo-Contreras, Fernando C Gómez-Merino
Diacylglycerol kinases (DGKs) are pivotal signaling enzymes that phosphorylate diacylglycerol (DAG) to yield phosphatidic acid (PA). The biosynthesis of PA from phospholipase D (PLD) and the coupled phospholipase C (PLC)/DGK route is a crucial signaling process in eukaryotic cells. Next to PLD, the PLC/DGK pathway is the second most important generator of PA in response to biotic and abiotic stresses. In eukaryotic cells, DGK, DAG, and PA are implicated in vital processes such as growth, development, and responses to environmental cues...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28223392/streptococcus-mitis-and-s-oralis-lack-a-requirement-for-cdsa-the-enzyme-required-for-synthesis-of-major-membrane-phospholipids-in-bacteria
#15
Hannah M Adams, Luke R Joyce, Ziqiang Guan, Ronda L Akins, Kelli L Palmer
Synthesis and integrity of the cytoplasmic membrane is fundamental to cellular life. Experimental evolution studies have hinted at unique physiology in the Gram-positive bacteria Streptococcus mitis and S. oralis These organisms commonly cause bacteremia and infectious endocarditis (IE) but are rarely investigated in mechanistic studies of physiology and evolution. Unlike other Gram-positive pathogens, high-level (MIC ≥ 256 μg/mL) daptomycin resistance rapidly emerges in S. mitis and S. oralis after a single drug exposure...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28223357/lipid-sensing-by-mtor-via-de-novo-synthesis-of-phosphatidic-acid
#16
Deepak Menon, Darin Salloum, Elyssa Bernfeld, Elizabeth Gorodetsky, Alla Akselrod, Maria A Frias, Jessica Sudderth, Pei-Hsuan Chen, Ralph DeBerardinis, David A Foster
mTOR, the mammalian target of rapamycin, integrates growth factor and nutrient signals to promote a transformation from catabolic to anabolic metabolism, cell growth, and cell cycle progression. Phosphatidic acid (PA)(2) interacts with the FRB (FK506 binding protein-12-rapamycin binding) domain of mTOR, which stabilizes both mTOR complexes - mTORC1 and mTORC2. We report here that mTORC1 and mTORC2 are activated in response to exogenously supplied fatty acids via the de novo synthesis of PA, a central metabolite for membrane phospholipid biosynthesis...
February 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28216107/an-endoplasmic-reticulum-engineered-yeast-platform-for-overproduction-of-triterpenoids
#17
Philipp Arendt, Karel Miettinen, Jacob Pollier, Riet De Rycke, Nico Callewaert, Alain Goossens
Saponins are a structurally diverse family of triterpenes that are widely found as main constituents in many traditional plant-based medicines and often have bioactivities of industrial interest. The heterologous production of triterpene saponins in microbes remains challenging and only limited successful pathway engineering endeavors have been reported. To improve the production capacities of a Saccharomyces cerevisiae saponin production platform, we assessed the effects of several hitherto unexplored gene knockout targets on the heterologous production of triterpenoids...
February 16, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28214728/lipid-signalling-mediated-by-pld-pa-modulates-proline-and-h2o2-levels-in-barley-seedlings-exposed-to-short-and-long-term-chilling-stress
#18
Micaela Peppino Margutti, Matias Reyna, María Verónica Meringer, Graciela E Racagni, Ana Laura Villasuso
Phospholipase D (PLD) hydrolyses phospholipids to yield phosphatidic acid (PA) and a head group, and is involved in responses to a variety of environmental stresses, including chilling and freezing stress. Barley responses to chilling stress (induced by incubating seedlings at 4 °C) are dynamic and the duration of stress, either short (0-180 min) or long-term (24-36 h) had a significant impact on the response. We investigated the roles of PLD/PA in responses of barley (Hordeum vulgare) seedlings to short and long-term chilling stress, based on regulation of proline and reactive oxygen species (ROS) levels...
February 10, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28209987/targeting-phospholipase-d-in-cancer-infection-and-neurodegenerative-disorders
#19
REVIEW
H Alex Brown, Paul G Thomas, Craig W Lindsley
Lipid second messengers have essential roles in cellular function and contribute to the molecular mechanisms that underlie inflammation, malignant transformation, invasiveness, neurodegenerative disorders, and infectious and other pathophysiological processes. The phospholipase D (PLD) isoenzymes PLD1 and PLD2 are one of the major sources of signal-activated phosphatidic acid (PtdOH) generation downstream of a variety of cell-surface receptors, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and integrins...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28199087/expression-purification-and-properties-of-a-human-arachidonoyl-specific-isoform-of-diacylglycerol-kinase
#20
William Jennings, Sejal Doshi, Prasanta Kumar Hota, Aaron Prodeus, Stephanie Black, Richard M Epand
Diacylglycerol kinase ε (DGKε) catalyzes the phosphorylation of diacylglycerol, producing phosphatidic acid. DGKε demonstrates exquisite specificity for the acyl chains of diacylglycerol. This contributes to the enrichment of particular acyl chains within the lipids of the phosphatidylinositol cycle. Phosphatidylinositol is highly enriched with 1-stearoyl-2-arachidonoyl, which is important for maintaining cellular health. Dysregulation of DGKε perturbs lipid signaling and biosynthesis, which has been linked to epilepsy, Huntington's disease, and heart disease...
February 24, 2017: Biochemistry
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