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Phosphatidic acid

Christopher T Boughter, Viviana Monje-Galvan, Wonpil Im, Jeffery B Klauda
In this study, the influence of cholesterol on lipid bilayers is investigated by changing phospholipid head group, cholesterol concentration, chain saturation, and temperature. Molecular dynamics (MD) simulations were used to characterize bilayers containing phosphatidylcholine (PC) head groups with either fully saturated dimyristoyl (DM) or monounsaturated dioleoyl (DO) acyl chains and cholesterol concentrations ranging from 5-50%. To further explore the effects of cholesterol on bilayers with different head groups, we also preformed MD simulations of bilayer systems having 15% cholesterol with phosphatidic acid (PA), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), and phosphatidylserine (PS), each having DM chains and at a temperature above the solid gel phase transition...
October 22, 2016: Journal of Physical Chemistry. B
Ra-Yeong Choi, Ju Ri Ham, Mi-Kyung Lee
This study investigated the effects and mechanism of esculetin (6,7-dihydroxycoumarin) on non-alcoholic fatty liver in diabetic mice fed high-fat diet (HFD). The diabetic mice model was induced by injection of streptozotocin, after which they were fed HFD diet with or without esculetin for 11 weeks. Non-diabetic mice were provided a normal diet. Diabetes induced hepatic hypertrophy, lipid accumulation and droplets; however, esculetin reversed these changes. Esculetin treatment in diabetic mice fed HFD significantly down-regulated expression of lipid synthesis genes (Fasn, Dgat2 and Pap) and inflammation genes (Tlr4, Myd88, Nfkb, Tnfα and Il6)...
October 18, 2016: Chemico-biological Interactions
Qing Chang, Rui Geng, Shanzheng Wang, Ding Qu, Xiangfei Kong
Treatment for multiple myeloma (MM) with a combined strategy of bone and tumor targeting remains a crucial technical challenge due to the incorporation of various functional components into one single system. Here, we developed dioleoyl phosphatidic acid (DOPA)-based paclitaxel (PTX)-loaded liposomes with modifications of alendronate and transferrin (Ald-/Tf-modified PTX-L), which were capable of bone affinity mediated by phosphate groups in DOPA and alendronate, and tumor targeting offered by transferrin. Ald-/Tf-modified PTX-L had clear and well-defined spherical shape with an intermediated size of 118...
October 17, 2016: Drug Delivery
Kyosei Urafuji, Manabu Arioka
In mammals, three types of intracellular phospholipase A1 (iPLA1) enzymes have been characterized and are thought to be involved in various cellular processes such as phospholipid metabolism, organelle biogenesis, and membrane trafficking. In this study we analyzed the unique iPLA1-like protein, Yor022c, in the budding yeast Saccharomyces cerevisiae. By the mass spectrometry analysis, we demonstrate that Yor022c is actually a phospholipase displaying sn-1-specific activity toward phosphatidylcholine, phosphatidylethanolamine, and phosphatidic acid, generating 2-acyl lysophospholipids...
October 13, 2016: Biochemical and Biophysical Research Communications
Derell Hardman, Daniel McFalls, Stylianos Fakas
Phosphatidic acid phosphatase (PAP) catalyzes the committed step of triacylglycerol (TAG) biosynthesis and thus regulates the amounts of TAG produced by the cell. TAG is the target of biotechnological processes developed for the production of food lipids or biofuels. These processes are using oleaginous microorganisms like the yeast Yarrowia lipolytica as the TAG producers. Thus manipulating key enzymatic activities like PAP in Y. lipolytica could drive lipid biosynthesis towards TAG production and increase TAG yields...
October 15, 2016: Yeast
Evan M Kerek, Elmar J Prenner
Following intake and absorption of Cd into the bloodstream, one possible target is the lipid membrane surrounding erythrocytes as well as kidney and liver cells where Cd accumulates. We investigated the interactions of Cd with model membranes from a biophysical perspective by using fluorescence spectroscopy and dynamic light scattering to monitor changes in liposome size, membrane fluidity and lipid phase transition. The fluorescent probe Laurdan was incorporated into liposomes and used to quantitate cadmium induced fluidity changes in model systems hydrated in 20mM HEPES, 100mM NaCl pH7...
October 11, 2016: Biochimica et Biophysica Acta
Alessandro Poli, Roberta Fiume, Gianluca Baldanzi, Daniela Capello, Stefano Ratti, Marco Gesi, Lucia Manzoli, Andrea Graziani, Pann-Ghill Suh, Lucio Cocco, Matilde Y Follo
Phosphatidylinositol (PI) signalling is an essential regulator of cell motility and proliferation. A portion of PI metabolism and signalling takes place in the nuclear compartment of eukaryotic cells, where an array of kinases and phosphatases localize and modulate PI. Among these, Diacylglycerol Kinases (DGKs) are a class of phosphotransferases that phosphorylate diacylglycerol and induce the synthesis of phosphatidic acid. Nuclear DGKalpha modulates cell cycle progression, and its activity or expression can lead to changes in the phosphorylated status of the Retinoblastoma protein, thus impairing G1/S transition and, subsequently, inducing cell cycle arrest, which is often uncoupled with apoptosis or autophagy induction...
October 12, 2016: Journal of Cellular Physiology
Jin Young Kim, Garam Kim, Sung-Chul Lim, Hong Seok Choi
LPIN1 is a protein that exhibits dual functions as a phosphatidic acid phosphatase enzyme in regulation of triglyceride and glycerophospholipid metabolism and a transcriptional coregulator. Through unknown tumour-promoting mechanism, LPIN1 frequently observed in various human cancer cell lines controls main cellular processes involved in cancer progression. Here, we demonstrate that LPIN1 enhances the tumour-promoting function of insulin receptor substrate 1 (IRS1) by controlling IRS1 stability. LPIN1 interacts with IRS1 in an insulin growth factor-1-dependent signalling pathway and inhibits its serine phosphorylation, and thereby eliminating ubiquitin-dependent degradation of IRS1 via proteasomal and lysosomal pathways...
October 11, 2016: Carcinogenesis
Wataru Matsuzaki, Hiromasa Takahashi, Hiroyuki Nakamura, Toshihiko Murayama
Ceramide kinase (CerK) and ceramide-1-phosphate (C1P) are involved in various cellular functions, while regulation of the enzyme activity has not been well elucidated. We herein investigated the effects of several glycerophospholipids on human recombinant CerK activity with CaCl2 and MgCl2 by measuring the formation of fluorescent labeled C1P in vitro. CerK activities were 44.1±11.4 (pmol/µg/min) with vehicle, 137±29 with 2 mM CaCl2, and 144±32 with 2 mM MgCl2 in the glycerol/albumin buffer. The addition of glycerophospholipids such as phosphatidylcholine, phosphatidylinositol (PI), PI 4,5-bisphosphate (PI(4,5)P2), and phosphatidic acid had no effect on CerK activity with CaCl2, although PI(4,5)P2 and phosphatidic acid bound to CerK in the lipid-protein overlay assay...
2016: Biological & Pharmaceutical Bulletin
Sara L Morales-Lázaro, Itzel Llorente, Félix Sierra-Ramírez, Ana E López-Romero, Miguel Ortíz-Rentería, Barbara Serrano-Flores, Sidney A Simon, León D Islas, Tamara Rosenbaum
The transient receptor potential vanilloid 1 (TRPV1) ion channel is mainly found in primary nociceptive afferents whose activity has been linked to pathophysiological conditions including pain, itch and inflammation. Consequently, it is important to identify naturally occurring antagonists of this channel. Here we show that a naturally occurring monounsaturated fatty acid, oleic acid, inhibits TRPV1 activity, and also pain and itch responses in mice by interacting with the vanilloid (capsaicin)-binding pocket and promoting the stabilization of a closed state conformation...
October 10, 2016: Nature Communications
Isabel Mérida, Pedro Torres-Ayuso, Antonia Ávila-Flores, Javier Arranz-Nicolás, Elena Andrada, María Tello-Lafoz, Rosa Liébana, Raquel Arcos
Diacylglycerol kinases (DGK) are a family of enzymes that catalyze the transformation of diacylglycerol into phosphatidic acid. In T lymphocytes, DGKα and ζ limit the activation of the PLCγ/Ras/ERK axis, providing a critical checkpoint to inhibit T cell responses. Upregulation of these isoforms limits Ras activation, leading to hypo-responsive, anergic states similar to those caused by tumors. Recent studies have identified DGKα upregulation in tumor lymphocyte infiltrates, and cells from DGKα and ζ deficient mice show enhanced antitumor activity, suggesting that limitation of DAG based signals by DGK is used by tumors to evade immune attack...
September 23, 2016: Advances in Biological Regulation
So Young Lee, Yun Young Lee, Joong Sub Choi, Mee-Sup Yoon, Joong-Soo Han
Decidualization of human endometrial stromal cells (hESCs) is crucial for successful uterine implantation and maintaining pregnancy. We previously reported that phospholipase D1 (PLD1) is required for cAMP-induced decidualization of hESCs. However, the mechanism by which phosphatidic acid (PA), the product of PLD1 action, might regulate decidualization is not known. We confirmed that PA induced decidualization of hESCs by observing morphological changes and measuring increased levels of decidualization markers such as IGFBP1 and prolactin transcripts (P < 0...
October 3, 2016: FEBS Journal
Becky Tu-Sekine, Hana L Goldschmidt, Daniel M Raben
Diacylglycerol kinases (DGKs) are a family of enzymes that catalyze the ATP-dependent phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PtdOH). The recognition of the importance of these enzymes has been increasing ever since it was determined that they played a role in the phosphatidylinositol (PtdIns) cycle and a number of excellent reviews have already been written [(see van Blitterswijk and Houssa, 2000; Kanoh et al., 2002; Mérida et al., 2008; Tu-Sekine and Raben, 2009, 2011; Shulga et al...
2016: Frontiers in Cell and Developmental Biology
Daniel M Raben, Casey N Barber
Lipids play a vital role in the health and functioning of neurons and interest in the physiological role of neuronal lipids is certainly increasing. One neuronal function in which neuronal lipids appears to play key roles in neurotransmission. Our understanding of the role of lipids in the synaptic vesicle cycle and neurotransmitter release is becoming increasingly more important. Much of the initial research in this area has highlighted the major roles played by the phosphoinositides (PtdIns), diacylglycerol (DAG), and phosphatidic acid (PtdOH)...
September 20, 2016: Advances in Biological Regulation
Jiayou Wang, Chunki Kim, Alvin Jogasuria, Yoonhee Han, Xudong Hu, Jiashin Wu, Hong Shen, Roman Chrast, Brian N Finck, Min You
Lipin-1 is a phosphatidate phosphohydrolase (PAP) required for the generation of diacylglycerol during glycerolipid synthesis, and exhibits dual functions in the regulation of lipid metabolism. Lipin-1 has been implicated in the pathogenesis of alcoholic liver disease (ALD). In the present study, we assessed lipin-1 function in myeloid cells in ALD using a myeloid cell-specific lipin-1 knockout (mLipin-1KO) mouse model. Utilizing the Gao-binge ethanol feeding protocol, matched mLipin-1KO mice and littermate loxP control (WT) mice were pair-fed with either an ethanol-containing diet or an ethanol-free diet (control)...
September 26, 2016: Scientific Reports
Xiaohong Zhuang, Eder M Dávila-Contreras, Andrew H Beaven, Wonpil Im, Jeffery B Klauda
Previous MD simulations of six phosphocholine (PC) lipid bilayers demonstrated the accuracy of the CHARMM36 force field (C36FF) for PC bilayer simulation at varied temperatures (BBA-Biomembranes, 1838 (2014): 2520-2529). In this work, we further examine the accuracy of C36FF over a wide temperature range for a broader range of lipid types such as various head groups (phosphatidic acid (PA), PC, phosphoethanolamine (PE), phosphoglycerol (PG), and phosphoserine (PS)), and tails (saturated, mono-, mixed- and poly-unsaturated acyl chains with varied chain lengths)...
September 21, 2016: Biochimica et Biophysica Acta
Marc Kvansakul, Fung T Lay, Christopher G Adda, Prem K Veneer, Amy A Baxter, Thanh Kha Phan, Ivan K H Poon, Mark D Hulett
Defensins are cationic antimicrobial peptides that serve as important components of host innate immune defenses, often by targeting cell membranes of pathogens. Oligomerization of defensins has been linked to their antimicrobial activity; however, the molecular basis underpinning this process remains largely unclear. Here we show that the plant defensin NsD7 targets the phospholipid phosphatidic acid (PA) to form oligomeric complexes that permeabilize PA-containing membranes. The crystal structure of the NsD7-PA complex reveals a striking double helix of two right-handed coiled oligomeric defensin fibrils, the assembly of which is dependent upon the interaction with PA at the interface between NsD7 dimers...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Eri Murakami, Takao Shionoya, Suguru Komenoi, Yuji Suzuki, Fumio Sakane
Diacylglycerol kinase (DGK) phosphorylates DG to generate phosphatidic acid. Recently, we found that a new alternative splicing product of the DGKη gene, DGKη3, which lacks exon 26 encoding 31 amino acid residues, was expressed only in the secondary spermatocytes and round spermatids of the testis. In this study, we cloned the full length DGKη3 gene and confirmed the endogenous expression of its protein product. During the cloning procedure, we found a new testis-specific alternative splicing product of the DGKη gene, DGKη4, which lacks half of the catalytic domain...
2016: PloS One
Yoshihiro Adachi, Kie Itoh, Tatsuya Yamada, Kara L Cerveny, Takamichi L Suzuki, Patrick Macdonald, Michael A Frohman, Rajesh Ramachandran, Miho Iijima, Hiromi Sesaki
Mitochondria divide to control their size, distribution, turnover, and function. Dynamin-related protein 1 (Drp1) is a critical mechanochemical GTPase that drives constriction during mitochondrial division. It is generally believed that mitochondrial division is regulated during recruitment of Drp1 to mitochondria and its oligomerization into a division apparatus. Here, we report an unforeseen mechanism that regulates mitochondrial division by coincident interactions of Drp1 with the head group and acyl chains of phospholipids...
September 15, 2016: Molecular Cell
David F Kashatus
In this issue of Molecular Cell, Adachi et al. (2016) describe a novel interaction between the mitochondrial fission GTPase Drp1 and phosphatidic acid that restrains Drp1 activity and shifts the balance toward mitochondrial fusion, adding another layer of complexity to the regulation of mitochondrial dynamics.
September 15, 2016: Molecular Cell
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