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Lipid mediators

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https://www.readbyqxmd.com/read/28108526/vaps-and-acbd5-tether-peroxisomes-to-the-er-for-peroxisome-maintenance-and-lipid-homeostasis
#1
Rong Hua, Derrick Cheng, Étienne Coyaud, Spencer Freeman, Erminia Di Pietro, Yuqing Wang, Adriano Vissa, Christopher M Yip, Gregory D Fairn, Nancy Braverman, John H Brumell, William S Trimble, Brian Raught, Peter K Kim
Lipid exchange between the endoplasmic reticulum (ER) and peroxisomes is necessary for the synthesis and catabolism of lipids, the trafficking of cholesterol, and peroxisome biogenesis in mammalian cells. However, how lipids are exchanged between these two organelles is not understood. In this study, we report that the ER-resident VAMP-associated proteins A and B (VAPA and VAPB) interact with the peroxisomal membrane protein acyl-CoA binding domain containing 5 (ACBD5) and that this interaction is required to tether the two organelles together, thereby facilitating the lipid exchange between them...
January 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28108524/acbd5-and-vapb-mediate-membrane-associations-between-peroxisomes-and-the-er
#2
Joseph L Costello, Inês G Castro, Christian Hacker, Tina A Schrader, Jeremy Metz, Dagmar Zeuschner, Afsoon S Azadi, Luis F Godinho, Victor Costina, Peter Findeisen, Andreas Manner, Markus Islinger, Michael Schrader
Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO-ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells...
January 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28108410/ganoderma-atrum-polysaccharide-ameliorates-anoxia-reoxygenation-mediated-oxidative-stress-and-apoptosis-in-human-umbilical-vein-endothelial-cells
#3
Yan-Song Zhang, Wen-Juan Li, Xian-Yi Zhang, Yu-Xin Yan, Shao-Ping Nie, De-Ming Gong, Xiao-Fang Tang, Ming He, Ming-Yong Xie
Ganoderma atrum polysaccharide (PSG-1), a main polysaccharide from Ganoderma atrum, possesses potent antioxidant capacity and cardiovascular benefits. The aim of this study was to investigate the role of PSG-1 in oxidative stress and apoptosis in human umbilical vein endothelial cells (HUVECs) under anoxia/reoxygenation (A/R) injury conditions. The results showed that exposure of HUVECs to A/R triggered cell death and apoptosis. Administration of PSG-1 significantly inhibited A/R-induced cell death and apoptosis in HUVECs...
January 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28108330/pleiotropic-responses-to-methionine-restriction
#4
Gene Ables, Jay Johnson
Methionine restriction (MR) extends lifespan across different species. The main responses of rodent models to MR are well-documented in adipose tissue (AT) and liver, which have reduced mass and improved insulin sensitivity, respectively. Recently, molecular mechanisms that improve healthspan have been identified in both organs during MR. In fat, MR induced a futile lipid cycle concomitant with beige AT accumulation, producing elevated energy expenditure. In liver, MR upregulated fibroblast growth factor 21 and improved glucose metabolism in aged mice and in response to a high-fat diet...
January 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28108297/the-leukotriene-b4-and-its-receptor-blt1-act-as-critical-drivers-of-neutrophil-recruitment-in-murine-bullous-pemphigoid-like-epidermolysis-bullosa-acquisita
#5
Tanya Sezin, Matthias Krajewski, Adam Wutkowski, Sadegh Mousavi, Lenche Chakievska, Katja Bieber, Ralf J Ludwig, Markus Dahlke, Dirk Rades, Franziska S Schulze, Enno Schmidt, Kathrin Kalies, Yask Gupta, Paul Schilf, Saleh M Ibrahim, Peter König, Dominik Schwudke, Detlef Zillikens, Christian D Sadik
Recruitment of neutrophils and eosinophils into the skin is a hallmark of pemphigoid diseases. The molecular cues regulating granulocyte recruitment into the skin as well as the individual contribution of neutrophils and eosinophils to pemphigoid diseases are, however, poorly understood. The lipid mediator leukotriene B4 (LTB4) is a potent granulocyte chemoattractant and abundant in the skin blister fluid of bullous pemphigoid (BP) patients, but its pathogenic significance is unknown. Using mouse models of (BP)-like epidermolysis bullosa acquisita (EBA) and of BP, we show that LTB4 and its receptor BLT1 act as critical drivers of neutrophil entry into the skin upon antibody deposition at the dermal-epidermal junction...
January 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28108259/appls-more-than-just-adiponectin-receptor-binding-proteins
#6
REVIEW
Zhuoying Liu, Ting Xiao, Xiaoyu Peng, Guangdi Li, Fang Hu
APPLs (adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif) are multifunctional adaptor proteins that bind to various membrane receptors, nuclear factors and signaling proteins to regulate many biological activities and processes, such as cell proliferation, chromatin remodeling, endosomal trafficking, cell survival, cell metabolism and apoptosis. APPL1, one of the APPL isoforms, was the first identified protein and interacts directly with adiponectin receptors to mediate adiponectin signaling to enhance lipid oxidation and glucose uptake...
January 17, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28106777/neuroprotection-by-caffeine-in-hyperoxia-induced-neonatal-brain-injury
#7
Stefanie Endesfelder, Ulrike Weichelt, Evelyn Strauß, Anja Schlör, Marco Sifringer, Till Scheuer, Christoph Bührer, Thomas Schmitz
Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term "oxygen radical disease of prematurity". Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106725/bacterial-responses-to-glyoxal-and-methylglyoxal-reactive-electrophilic-species
#8
REVIEW
Changhan Lee, Chankyu Park
Glyoxal (GO) and methylglyoxal (MG), belonging to α-oxoaldehydes, are produced by organisms from bacteria to humans by glucose oxidation, lipid peroxidation, and DNA oxidation. Since glyoxals contain two adjacent reactive carbonyl groups, they are referred to as reactive electrophilic species (RES), and are damaging to proteins and nucleotides. Therefore, glyoxals cause various diseases in humans, such as diabetes and neurodegenerative diseases, from which all living organisms need to be protected. Although the glyoxalase system has been known for some time, details on how glyoxals are sensed and detoxified in the cell have not been fully elucidated, and are only beginning to be uncovered...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106559/abca1-deficiency-affects-basal-cognitive-deficits-and-dendritic-density-in-mice
#9
Nicholas F Fitz, Alexis Y Carter, Victor Tapias, Emilie L Castranio, Ravindra Kodali, Iliya Lefterov, Radosveta Koldamova
ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-free apolipoproteins and regulates the generation of high density lipoproteins. Previously, we have shown that lack of Abca1 significantly increases amyloid deposition and cognitive deficits in Alzheimer's disease model mice expressing human amyloid-β protein precursor (APP). The goal of this study was to determine if ABCA1 plays a role in memory deficits caused by amyloid-β (Aβ) oligomers and examine neurite architecture of pyramidal hippocampal neurons...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106399/-1-h-nmr-shows-slow-phospholipid-flip-flop-in-gel-and-fluid-bilayers
#10
Drew Marquardt, Frederick A Heberle, Tatiana Miti, Barbara Eicher, Erwin London, John Katsaras, Georg Pabst
We measured the transbilayer diffusion of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in large unilamellar vesicles in both the gel (Lβ') and fluid (Lα) phases. The choline resonance of headgroup-protiated DPPC exchanged into the outer leaflet of headgroup-deuterated DPPC-d13 vesicles was monitored using (1)H NMR spectroscopy coupled with the addition of a paramagnetic shift reagent. This allowed us to distinguish between the inner and outer leaflet DPPC, and determine the flip-flop rate as a function of temperature...
January 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28104921/effects-of-gold-nanoparticles-on-lipid-packing-and-membrane-pore-formation
#11
Anupama Bhat, Lance W Edwards, Xiao Fu, Dillon L Badman, Samuel Huo, Albert J Jin, Qi Lu
Gold nanoparticles (AuNPs) have been increasingly integrated in biological systems, making it imperative to understand their interactions with cell membranes, the first barriers to be crossed to enter cells. Herein, liposomes composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) as a model membrane system were treated with citrate stabilized AuNPs from 5 to 30 nm at various concentrations. The fluorescence shifts of Laurdan probes reveal that AuNPs in general made liposomes more fluidic. The increased fluidity is expected to result in an increased surface area, and thus liposome shape changes from circular to less circular, which was further confirmed with fluorescence microscopy...
December 26, 2016: Applied Physics Letters
https://www.readbyqxmd.com/read/28104689/identification-of-apilimod-as-a-first-in-class-pikfyve-kinase-inhibitor-for-treatment-of-b-cell-non-hodgkin-lymphoma
#12
Sophia Gayle, Sean Landrette, Neil Beeharry, Chris Conrad, Marylens Hernandez, Paul Beckett, Shawn M Ferguson, Talya Mandelkern, Meiling Zheng, Tian Xu, Jonathan Rothberg, Henri Lichenstein
We identified apilimod as an anti-proliferative compound by high-throughput screening of clinical stage drugs. Apilimod exhibits exquisite specificity for PIKfyve lipid kinase and has selective cytotoxic activity in B-cell non-Hodgkin lymphoma (B-NHL) compared to normal cells. Apilimod displays nanomolar activity in vitro, and in vivo studies demonstrate single agent efficacy as well as synergy with approved B-NHL drugs. Using biochemical and knockdown approaches, and discovery of a kinase domain mutation conferring resistance, we demonstrate that apilimod-mediated cytotoxicity is driven by PIKfyve inhibition...
January 19, 2017: Blood
https://www.readbyqxmd.com/read/28104445/the-sh3-domain-of-caskin1-binds-to-lysophosphatidic-acid-suggesting-a-direct-role-for-the-lipid-in-intracellular-signaling
#13
Kitti Koprivanacz, Orsolya Tőke, Balázs Besztercei, Tünde Juhász, László Radnai, Balázs Merő, Judith Mihály, Mária Péter, Gábor Balogh, László Vígh, László Buday, Károly Liliom
Src homology 3 or SH3 domains constitute one of the most common protein domains in signal transduction, generally characterized by their binding to proline-rich sequences on interacting signaling proteins. Caskin1, a scaffold protein regulating cortical actin filaments, enriched in neural synapses in mammals, has an atypical SH3 domain. Key aromatic residues necessary for ligand binding that are present in canonical SH3 domains are missing from Caskin1 SH3. In concordance, proline-rich interacting partner could not be identified yet...
January 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28104376/lipidomic-profile-of-gm95-cell-death-induced-by-clostridium-perfringens-alpha-toxin
#14
Marco M Manni, Juan G Valero, Miriam Pérez-Cormenzana, Ainara Cano, Cristina Alonso, Félix M Goñi
Clostridium perfringens alpha-toxin (ATX) is considered as a prototype of cytotoxic bacterial phospholipases C, and is the major virulence factor in C. perfringens-induced gas gangrene. It is known that, depending on the dose, ATX causes membrane disruption and cytolysis or only limited hydrolysis of its substrates. In the latter case, toxin activity leads to the unregulated generation of bioactive lipids that can ultimately induce cell death. We have characterized apoptosis and necrosis in highly ATX-sensitive, ganglioside-deficient cells exposed to different concentrations of ATX and we have studied the lipidomic profile of cells treated with ATX as compared to native cells to detect the main changes in the lipidomic profile and the possible involvement of lipid signals in cell death...
January 16, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28103528/topical-vaccination-with-super-stable-ready-to-use-nanovesicles
#15
Ayelen Tatiana Caimi, Federico Parra, Marcelo Alexander de Farias, Rodrigo Villares Portugal, Ana Paula Perez, Eder Lilia Romero, Maria Jose Morilla
Ultradeformable archaeosomes (UDA) are nanovesicles made of total polar archaeolipids (TPA) from the archaea Halorubrum tebenquichense, soybean phosphatidylcholine and sodium cholate (3:3:1w/w). Fresh dispersions of UDA including different type of antigens are acknowledged as efficient topical vaccination agents. UDA dispersions however, if manufactured for pharmaceutical use, have to maintain colloidal stability upon liposomicidal processes such as sterilization and lyophilization (SLRUDA), needed to extend shelf life during storage...
December 26, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28103440/carbon-nanotubes-mediate-fusion-of-lipid-vesicles
#16
Ramachandra Moorthy Bhaskara, Stephanie M Linker, Martin Vögele, Juergen Koefinger, Gerhard Hummer
The fusion of lipid membranes is opposed by high energetic barriers. In living organisms, complex protein machineries carry out this biologically essential process. Here we show that membrane-spanning carbon nanotubes (CNTs) can trigger spontaneous fusion of small lipid vesicles. In coarse-grained molecular dynamics simulations, we find that a CNT bridging between two vesicles locally perturbs their lipid structure. Their outer leaflets merge as the CNT pulls lipids out of the membranes, creating an hourglass-shaped fusion intermediate with still intact inner leaflets...
January 19, 2017: ACS Nano
https://www.readbyqxmd.com/read/28102849/berberine-sonodynamic-therapy-induces-autophagy-and-lipid-unloading-in-macrophage
#17
Jiayuan Y Kou, Ying Li, Zhaoyu Y Zhong, Yueqing Q Jiang, Xuesong S Li, Xiaobo B Han, Zhongni N Liu, Ye Tian, Liming M Yang
Impaired autophagy in macrophages accompanies the progression of atherosclerosis and contributes to lipid loading in plaques and ineffective lipid degradation. Therefore, evoking autophagy and its associated cholesterol efflux may provide a therapeutic treatment for atherosclerosis. In the present study, berberine-mediated sonodynamic therapy (BBR-SDT) was used to induce autophagy and cholesterol efflux in THP-1 macrophages and derived foam cells. Following BBR-SDT, autophagy was increased in the macrophages, autophagy resistance in the foam cells was prevented, and cholesterol efflux was induced...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28101970/neuropeptide-y-resists-excess-loss-of-fat-by-lipolysis-in-calorie-restricted-mice-a-trait-potential-for-the-life-extending-effect-of-calorie-restriction
#18
Seongjoon Park, Toshimitsu Komatsu, Sang Eun Kim, Katsuya Tanaka, Hiroko Hayashi, Ryoichi Mori, Isao Shimokawa
Neuropeptide Y (NPY) is an orexigenic peptide that plays an essential role in caloric restriction (CR)-mediated lifespan extension. However, the mechanisms underlying the NPY-mediated effects in CR are poorly defined. Here, we report that NPY deficiency in male mice during CR increases mortality in association with lipodystrophy. NPY(-/-) mice displayed a rapid decrease in body weight and fat mass, as well as increased lipolysis during CR. These alterations in fat regulation were inhibited by the lipolysis inhibitor, acipimox, a treatment associated with reduced mortality...
January 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/28101696/role-of-the-helix-in-talin-f3-domain-f3-helix-in-talin-mediated-integrin-activation
#19
Ang Li, Qiang Guo, Ailin Wei, Yaliang Zhou, Weiming Hu
Increases in ligand binding to cellular integrins (activation) play an important role in platelet and leukocyte function. Talin is necessary in vivo and sufficient in vitro for integrin αIIbβ3 activation. The precise mechanisms by which talin activates integrin are still being elucidated. In particular, talin undergoes conformational changes (around the F3 helix) and inserts the F3 helix into lipid bilayer; however, the connection between this lipid-inserting mechanism of talin and talin's capacity to activate integrin has never been explored before...
January 18, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28101459/venlafaxine-induced-cytotoxicity-towards-isolated-rat-hepatocytes-involves-oxidative-stress-and-mitochondrial-lysosomal-dysfunction
#20
Elham Ahmadian, Hossein Babaei, Alireza Mohajjel Nayebi, Aziz Eftekhari, Mohammad Ali Eghbal
Purpose: Depression is a public disorder worldwide. Despite the widespread use of venlafaxine in the treatment of depression, it has been associated with the incidence of toxicities. Hence, the goal of the current investigation was to evaluate the mechanisms of venlafaxine-induced cell death in the model of the freshly isolated rat hepatocytes. Methods: Collagenase-perfused rat hepatocytes were treated with venlafaxine and other agents. Cell damage, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential decline, lysosomal damage, glutathione (GSH) level were analyzed...
December 2016: Advanced Pharmaceutical Bulletin
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