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Ioanna Sevastou Eleanna KaffeMarios-Angelos Mouratis Vassilis Aidinis 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(1):42-60
Lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), the most prominent lysoglycerophospholipids, are emerging as a novel class of inflammatory lipids, joining thromboxanes, leukotrienes and prostaglandins with which they share metabolic pathways and regulatory mechanisms. Enzymes that participate in LPC and LPA metabolism, such as the phospholipase A2 superfamily (PLA2) and autotaxin (ATX, ENPP2), play central roles in regulating LPC and LPA levels and consequently their actions. LPC/LPA biosynthetic pathways will be briefly presented and LPC/LPA signaling properties and their possible functions in the regulation of the immune system and chronic inflammation will be reviewed. Furthermore, implications of exacerbated LPC and/or LPA signaling in the context of chronic inflammatory diseases, namely rheumatoid arthritis, multiple sclerosis, pulmonary fibrosis and hepatitis, will be discussed. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. 相似文献
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Natalie Lefort Zhengping Yi Benjamin Bowen Brian Glancy Eleanna A. De Filippis Rebekka Mapes Hyonson Hwang Charles R. Flynn Wayne T. Willis Anthony Civitarese Kurt Hjlund Lawrence J. Mandarino 《Journal of Proteomics》2009,72(6):1046
Mitochondria can be isolated from skeletal muscle in a manner that preserves tightly coupled bioenergetic function in vitro. The purpose of this study was to characterize the composition of such preparations using a proteomics approach. Mitochondria isolated from human vastus lateralis biopsies were functional as evidenced by their response to carbohydrate and fat-derived fuels. Using one-dimensional gel electrophoresis and HPLC-ESI-MS/MS, 823 unique proteins were detected, and 487 of these were assigned to the mitochondrion, including the newly characterized SIRT5, MitoNEET and RDH13. Proteins detected included 9 of the 13 mitochondrial DNA-encoded proteins and 86 of 104 electron transport chain (ETC) and ETC-related proteins. In addition, 59 of 78 proteins of the 55S mitoribosome, several TIM and TOM proteins and cell death proteins were present. This study presents an efficient method for future qualitative assessments of proteins from functional isolated mitochondria from small samples of healthy and diseased skeletal muscle. 相似文献
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The cabbage aphid: a walking mustard oil bomb 总被引:7,自引:0,他引:7
Kazana E Pope TW Tibbles L Bridges M Pickett JA Bones AM Powell G Rossiter JT 《Proceedings. Biological sciences / The Royal Society》2007,274(1623):2271-2277
The cabbage aphid, Brevicoryne brassicae, has developed a chemical defence system that exploits and mimics that of its host plants, involving sequestration of the major plant secondary metabolites (glucosinolates). Like its host plants, the aphid produces a myrosinase (beta-thioglucoside glucohydrolase) to catalyse the hydrolysis of glucosinolates, yielding biologically active products. Here, we demonstrate that aphid myrosinase expression in head/thoracic muscle starts during embryonic development and protein levels continue to accumulate after the nymphs are born. However, aphids are entirely dependent on the host plant for the glucosinolate substrate, which they store in the haemolymph. Uptake of a glucosinolate (sinigrin) was investigated when aphids fed on plants or an in vitro system and followed a different developmental pattern in winged and wingless aphid morphs. In nymphs of the wingless aphid morph, glucosinolate level continued to increase throughout the development to the adult stage, but the quantity in nymphs of the winged form peaked before eclosion (at day 7) and subsequently declined. Winged aphids excreted significantly higher amounts of glucosinolate in the honeydew when compared with wingless aphids, suggesting regulated transport across the gut. The higher level of sinigrin in wingless aphids had a significant negative impact on survival of a ladybird predator. Larvae of Adalia bipunctata were unable to survive when fed adult wingless aphids from a 1% sinigrin diet, but survived successfully when fed aphids from a glucosinolate-free diet (wingless or winged), or winged aphids from 1% sinigrin. The apparent lack of an effective chemical defence system in adult winged aphids possibly reflects their energetic investment in flight as an alternative predator avoidance mechanism. 相似文献
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Dominique Chu Eleanna Kazana Noémie Bellanger Tarun Singh Mick F Tuite Tobias von der Haar 《The EMBO journal》2014,33(1):21-34
Synonymous codons encode the same amino acid, but differ in other biophysical properties. The evolutionary selection of codons whose properties are optimal for a cell generates the phenomenon of codon bias. Although recent studies have shown strong effects of codon usage changes on protein expression levels and cellular physiology, no translational control mechanism is known that links codon usage to protein expression levels. Here, we demonstrate a novel translational control mechanism that responds to the speed of ribosome movement immediately after the start codon. High initiation rates are only possible if start codons are liberated sufficiently fast, thus accounting for the observation that fast codons are overrepresented in highly expressed proteins. In contrast, slow codons lead to slow liberation of the start codon by initiating ribosomes, thereby interfering with efficient translation initiation. Codon usage thus evolved as a means to optimise translation on individual mRNAs, as well as global optimisation of ribosome availability. 相似文献
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Tobias B. Haack Penelope Hogarth Michael C. Kruer Allison Gregory Thomas Wieland Thomas Schwarzmayr Elisabeth Graf Lynn Sanford Esther Meyer Eleanna Kara Stephan M. Cuno Sami I. Harik Vasuki H. Dandu Nardo Nardocci Giovanna Zorzi Todd Dunaway Mark Tarnopolsky Steven Skinner Steven Frucht Era Hanspal Connie Schrander-Stumpel Delphine Héron Cyril Mignot Barbara Garavaglia Kailash Bhatia John Hardy Tim M. Strom Nathalie Boddaert Henry H. Houlden Manju A. Kurian Thomas Meitinger Holger Prokisch Susan J. Hayflick 《American journal of human genetics》2012
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Mario Strazzabosco Romina Fiorotto Massimiliano Cadamuro Carlo Spirli Valeria Mariotti Eleanna Kaffe Roberto Scirpo Luca Fabris 《生物化学与生物物理学报:疾病的分子基础》2018,1864(4):1374-1379
The most studied physiological function of biliary epithelial cells (cholangiocytes) is to regulate bile flow and composition, in particular the hydration and alkalinity of the primary bile secreted by hepatocytes. After almost three decades of studies it is now become clear that cholangiocytes are also involved in epithelial innate immunity, in inflammation, and in the reparative processes in response to liver damage. An increasing number of evidence highlights the ability of cholangiocyte to undergo changes in phenotype and function in response to liver damage. By participating actively to the immune and inflammatory responses, cholangiocytes represent a first defense line against liver injury from different causes. Indeed, cholangiocytes express a number of receptors able to recognize pathogen- or damage-associated molecular patterns (PAMPs/DAMPs), such as Toll-like receptors (TLR), which modulate their pro-inflammatory behavior. Cholangiocytes can be both the targets and the initiators of the inflammatory process. Derangements of the signals controlling these mechanisms are at the basis of the pathogenesis of different cholangiopathies, both hereditary and acquired, such as cystic fibrosis-related liver disease and sclerosing cholangitis. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen. 相似文献
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Upon arrival at their synaptic targets, axons slow down their growth and extensively remodel before the assembly of presynaptic boutons. Wnt proteins are target-derived secreted factors that promote axonal remodelling and synaptic assembly. In the developing spinal cord, Wnts secreted by motor neurons promote axonal remodelling of NT-3 responsive dorsal root ganglia neurons. Axon remodelling induced by Wnts is characterised by growth cone pausing and enlargement, processes that depend on the re-organisation of microtubules. However, the contribution of the actin cytoskeleton has remained unexplored. Here, we demonstrate that Wnt3a regulates the actin cytoskeleton by rapidly inducing F-actin accumulation in growth cones from rodent DRG neurons through the scaffold protein Dishevelled-1 (Dvl1) and the serine-threonine kinase Gsk3β. Importantly, these changes in actin cytoskeleton occurs before enlargement of the growth cones is evident. Time-lapse imaging shows that Wnt3a increases lamellar protrusion and filopodia velocity. In addition, pharmacological inhibition of actin assembly demonstrates that Wnt3a increases actin dynamics. Through a yeast-two hybrid screen, we identified the actin-binding protein Eps8 as a direct interactor of Dvl1, a scaffold protein crucial for the Wnt signalling pathway. Gain of function of Eps8 mimics Wnt-mediated axon remodelling, whereas Eps8 silencing blocks the axon remodelling activity of Wnt3a. Importantly, blockade of the Dvl1-Eps8 interaction completely abolishes Wnt3a-mediated axonal remodelling. These findings demonstrate a novel role for Wnt-Dvl1 signalling through Eps8 in the regulation of axonal remodeling. 相似文献
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Ioanna Nikitopoulou Eleanna Kaffe Ioanna Sevastou Ivi Sirioti Martina Samiotaki Damian Madan Glenn D. Prestwich Vassilis Aidinis 《PloS one》2013,8(7)
Rheumatoid arthritis (RA) is a destructive arthropathy with systemic manifestations, characterized by chronic synovial inflammation. Under the influence of the pro-inflammatory milieu synovial fibroblasts (SFs), the main effector cells in disease pathogenesis become activated and hyperplastic while releasing a number of signals that include pro-inflammatory factors and tissue remodeling enzymes. Activated RA SFs in mouse or human arthritic joints express significant quantities of autotaxin (ATX), a lysophospholipase D responsible for the majority of lysophosphatidic acid (LPA) production in the serum and inflamed sites. Conditional genetic ablation of ATX from SFs resulted in attenuation of disease symptoms in animal models, an effect attributed to diminished LPA signaling in the synovium, shown to activate SF effector functions. Here we show that administration of 1-bromo-3(S)-hydroxy-4-(palmitoyloxy)butyl-phosphonate (BrP-LPA), a metabolically stabilized analog of LPA and a dual function inhibitor of ATX and pan-antagonist of LPA receptors, attenuates collagen induced arthritis (CIA) development, thus validating the ATX/LPA axis as a novel therapeutic target in RA. 相似文献