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Palmitoylation

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https://www.readbyqxmd.com/read/28546512/wnt5a-promotes-frizzled-4-signalosome-assembly-by-stabilizing-cysteine-rich-domain-dimerization
#1
Zachary J DeBruine, Jiyuan Ke, Kaleeckal G Harikumar, Xin Gu, Peter Borowsky, Bart O Williams, Wenqing Xu, Laurence J Miller, H Eric Xu, Karsten Melcher
Wnt/β-catenin signaling is activated when extracellular Wnt ligands bind Frizzled (FZD) receptors at the cell membrane. Wnts bind FZD cysteine-rich domains (CRDs) with high affinity through a palmitoylated N-terminal "thumb" and a disulfide-stabilized C-terminal "index finger," yet how these binding events trigger receptor activation and intracellular signaling remains unclear. Here we report the crystal structure of the Frizzled-4 (FZD4) CRD in complex with palmitoleic acid, which reveals a CRD tetramer consisting of two cross-braced CRD dimers...
May 25, 2017: Genes & Development
https://www.readbyqxmd.com/read/28533249/the-myxobacterial-metabolite-soraphen-a-inhibits-hiv-1-by-reducing-virus-production-and-altering-virion-composition
#2
Eric Fleta-Soriano, Katarína Smutná, Javier P Martinez, Cristina Lorca Oró, S Kashif Sadiq, Gilles Mirambeau, Carmen Lopez-Iglesias, Marta Bosch, Albert Pol, Mark Brönstrup, Juana Diez, Andreas Meyerhans
Soraphen A is a myxobacterial metabolite that blocks the acetyl-CoA carboxylase of the host, and was previously identified as a novel HIV inhibitor. Here we report that Soraphen A acts by reducing virus production and altering the gp120 virion content, impacting entry capacity and infectivity. These effects are partially reversed by addition of palmitic acid, suggesting inhibition of HIV Env palmitoylation as one of the mechanisms of antiviral action.
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28526873/role-of-s-palmitoylation-by-zdhhc13-in-mitochondrial-function-and-metabolism-in-liver
#3
Li-Fen Shen, Yi-Ju Chen, Kai-Ming Liu, Amir N Saleem Haddad, I-Wen Song, Hsiao-Yuh Roan, Li-Ying Chen, Jeffrey J Y Yen, Yu-Ju Chen, Jer-Yuarn Wu, Yuan-Tsong Chen
Palmitoyltransferase (PAT) catalyses protein S-palmitoylation which adds 16-carbon palmitate to specific cysteines and contributes to various biological functions. We previously reported that in mice, deficiency of Zdhhc13, a member of the PAT family, causes severe phenotypes including amyloidosis, alopecia, and osteoporosis. Here, we show that Zdhhc13 deficiency results in abnormal liver function, lipid abnormalities, and hypermetabolism. To elucidate the molecular mechanisms underlying these disease phenotypes, we applied a site-specific quantitative approach integrating an alkylating resin-assisted capture and mass spectrometry-based label-free strategy for studying the liver S-palmitoylome...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526869/blocking-of-carnitine-palmitoyl-transferase-1-potently-reduces-stress-induced-depression-in-rat-highlighting-a-pivotal-role-of-lipid-metabolism
#4
Anne Skøttrup Mørkholt, Ove Wiborg, Jette G K Nieland, Søren Nielsen, John Dirk Nieland
Major depressive disorder is a complex and common mental disease, for which the pathology has not been elucidated. The purpose of this study is to provide knowledge about the importance of mitochondrial dysfunction, dysregulated lipid metabolism and inflammation. Mitochondrial carnitine palmitoyl transferase 1a (CPT1a) is a key molecule involved in lipid metabolism and mutations in CPT1a causing reduced function is hypothesized to have a protective role in the development of depression. Moreover, CPT1a is found to be upregulated in suicide patients with history of depression...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526602/palmitoyl-ascorbate-and-doxorubicin-co-encapsulated-liposome-for-synergistic-anticancer-therapy
#5
Yue Yang, Xiaoyu Lu, Qi Liu, Yu Dai, Xiaojie Zhu, Yanli Wen, Jiaqiu Xu, Yang Lu, Di Zhao, Xijing Chen, Ning Li
Combination therapy with two drugs and nanoparticle-based drug delivery systems are widely applied to reduce the adverse effects of traditional treatment by chemotherapeutic drugs. Palmitoyl ascorbate (PA) as a lipophilic derivative of ascorbic acid shows the advantages in cancer treatment. The aim of the study was to prepare a doxorubicin (DOX) and PA co-loaded liposome to synergistically treat tumor and effectively alleviate the toxicity caused by DOX. The effects were evaluated by in vitro and in vivo studies...
May 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28526339/magnesium-isoglycyrrhizinate-blocks-fructose-induced-hepatic-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-activation-and-lipid-metabolism-disorder
#6
Xiao-Juan Zhao, Yan-Zi Yang, Yan-Jing Zheng, Shan-Chun Wang, Hong-Mei Gu, Ying Pan, Shui-Juan Wang, Hong-Jiang Xu, Ling-Dong Kong
Magnesium isoglycyrrhizinate as a hepatoprotective agent possesses immune modulation and anti-inflammation, and treats liver diseases. But its effects on immunological-inflammatory and metabolic profiles for metabolic syndrome with liver injury and underlying potential mechanisms are not fully understood. In this study, magnesium isoglycyrrhizinate alleviated liver inflammation and lipid accumulation in fructose-fed rats with metabolic syndrome. It also suppressed hepatic inflammatory signaling activation by reducing protein levels of phosphorylation of nuclear factor-kappa B p65 (p-NF-κB p65), inhibitor of nuclear factor kappa-B kinase α/β (p-IKKα/β) and inhibitor of NF-κB α (p-IκBα) as well as nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase-1 in rats, being consistent with its reduction of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 levels...
May 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28522438/anti-inflammatory-effects-of-oxpapc-involve-endothelial-cell-mediated-generation-of-lxa4
#7
Yunbo Ke, Noureddine Zebda, Olga Oskokova, Taras Afonyushkin, Evgeny Berdyshev, Yufeng Tian, Fanyong Meng, Nicolene Sarich, Valery N Bochkov, Ji Ming Wang, Anna A Birukova, Konstantin G Birukov
Rationale: Oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine generates a group of bioactive oxidized phospholipid products (OxPAPC) with a broad range of biological activities. Barrier-enhancing and anti-inflammatory effects of OxPAPC on pulmonary endothelial cells (EC) are critical for prevention of acute lung injury caused by bacterial pathogens or excessive mechanical ventilation. Anti-inflammatory properties of OxPAPC are associated with its antagonistic effects on toll-like receptors and suppression of RhoA GTPase signaling...
May 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28521134/dynamic-palmitoylation-targets-map6-to-the-axon-to-promote-microtubule-stabilization-during-neuronal-polarization
#8
Elena Tortosa, Youri Adolfs, Masaki Fukata, R Jeroen Pasterkamp, Lukas C Kapitein, Casper C Hoogenraad
Microtubule-associated proteins (MAPs) are main candidates to stabilize neuronal microtubules, playing an important role in establishing axon-dendrite polarity. However, how MAPs are selectively targeted to specific neuronal compartments remains poorly understood. Here, we show specific localization of microtubule-associated protein 6 (MAP6)/stable tubule-only polypeptide (STOP) throughout neuronal maturation and its role in axonal development. In unpolarized neurons, MAP6 is present at the Golgi complex and in secretory vesicles...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28515233/wntless-sec12-complex-on-er-membrane-regulates-early-wnt-secretory-vesicle-assembly-and-mature-ligand-export
#9
Jiaxin Sun, Shiyan Yu, Xiao Zhang, Catherine Capac, Onyedikachi Aligbe, Timothy Daudelin, Edward M Bonder, Nan Gao
Wntless (Wls) transports Wnt molecules for secretion, however the cellular mechanism underlying the initial assembly of Wnt secretory vesicles is still not fully defined. Using proteomic and mutagenic analyses of the mammalian Wls, we report a mechanism for formation of early Wnt secretory vesicle on ER membrane. Wls forms a complex with SEC12, an ER membrane-localized GEF activator of SAR1 small GTPase. Compared to palmitoylation-deficient Wnt molecules, binding of mature Wnt to Wls increases Wls-SEC12 interaction and promotes Wls association with SAR1, the key activator of the COPII machinery...
May 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28514835/genistein-has-beneficial-effects-on-hepatic-steatosis-in-high-fat-high-sucrose-diet-treated-rats
#10
Huanhuan Liu, Huijia Zhong, Yimin Yin, Zhuoqin Jiang
Genistein, a kind of phytoestrogen abundant in soybeans, is beneficial for alleviating non-alcoholic fatty liver disease (NAFLD), but the specific mechanism was not clearly understood. This study was designed to determine the effect of genistein on NAFLD and explore the possible mechanism. 36 male Sprague-Dawley rats were divided into 4 groups: the control group, high fat-high sucrose diet (HFS) group, HFS with 4mg/kg body weight genistein, and HFS with 8mg/kg body weight genistein. 12 weeks later, serum and hepatic lipid profiles, liver histopathological examination were characterized...
May 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28510438/complex-effects-of-24-1-sphingolipids-in-membranes-containing-dioleoyl-phosphatidylcholine-and-cholesterol
#11
Aritz B Garcia-Arribas, Emilio J Gonzalez-Ramirez, Jesús Sot, Itziar Areso, Alicia Alonso, Felix M Goni
The effects of C24:1 sphingolipids have been tested in phospholipid bilayers containing cholesterol. Confocal microscopy, differential scanning calorimetry, and atomic force microscopy imaging and force curves have been used. More precisely, the effects of C24:1 ceramide (nervonoyl ceramide, nCer) were evaluated and compared to those of C16:0 ceramide (palmitoyl ceramide, pCer) in bilayers composed basically of dioleoyl phosphatidylcholine, sphingomyelin (either C24:1, nSM or C16:0, pSM) and cholesterol. Combination of equimolecular amounts of C24:1 and C16:0 sphingolipids were also studied under the same conditions...
May 16, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28494640/identification-of-3-mcpd-esters-to-verify-the-adulteration-of-extra-virgin-olive-oil
#12
Wei-Ching Hung, Guan-Jhih Peng, Wen-Ju Tsai, Mei-Hua Chang, Chia-Ding Liao, Su-Hsiang Tseng, Ya-Min Kao, Der-Yuan Wang, Hwei-Fang Cheng
Abstracts The adulteration of olive oil is an important issue around the world. This paper reports an indirect method by which to identify 3-monochloropropane-1,2-diol esters (3-MCPD esters) in olive oils. Following sample preparation, the samples were spiked with 1,2-bis-palmitoyl-3-chloropropanediol standard for analysis using gas chromatograph-tandem mass spectrometry. The total recovery ranged from 102.8 to 105.5%, the coefficient of variation ranged from 1.1 to 10.1%, and the limit of quantification was 0...
May 12, 2017: Food Additives & Contaminants. Part B, Surveillance
https://www.readbyqxmd.com/read/28492915/sildenafil-treatment-in-heart-failure-with-preserved-ejection-fraction-targeted-metabolomic-profiling-in-the-relax-trial
#13
Hanghang Wang, Kevin Anstrom, Olga Ilkayeva, Michael J Muehlbauer, James R Bain, Steven McNulty, Christopher B Newgard, William E Kraus, Adrian Hernandez, G Michael Felker, Margaret Redfield, Svati H Shah
Importance: Phosphodiesterase-5 inhibition with sildenafil compared with a placebo had no effect on the exercise capacity or clinical status of patients with heart failure with preserved ejection fraction (HFpEF) in the PhosphodiesteRasE-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure with Preserved Ejection Fraction (RELAX) clinical trial. Metabolic impairments may explain the neutral results. Objective: To test the hypothesis that profiling metabolites in the RELAX trial would clarify the mechanisms of sildenafil effects and identify metabolites associated with clinical outcomes in HFpEF...
May 10, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28490875/mechanism-of-transdermal-permeation-promotion-of-lipophilic-drugs-by-ethosomes
#14
Li Yang, Lifang Wu, Dongze Wu, Deshun Shi, Tai Wang, Xiaoliang Zhu
Ethosomes can promote the penetration of lipophilic drugs into the skin, but the underlying mechanism is still unknown. The purpose of this study was to investigate the mechanism of transdermal permeation promotion of lipophilic drugs by ethosomes. The formulation of ethosomes was optimized using the Box-Behnken experimental design, in which Rhodamine B and 1-palmitoyl-2-{12-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl}-sn-glycero-3-phosphocholine were used to simulate a model lipophilic drug and act as a fluorescent tracer of ethosomal phospholipids, respectively...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28489334/diagnosis-of-copan-by-whole-exome-sequencing-waking-up-a-sleeping-tiger-s-eye
#15
Christina Evers, Angelika Seitz, Birgit Assmann, Thomas Opladen, Stephanie Karch, Katrin Hinderhofer, Martin Granzow, Nagarajan Paramasivam, Roland Eils, Nicolle Diessl, Claus R Bartram, Ute Moog
Neurodegeneration with brain iron accumulation (NBIA) is a group of neurodegenerative disorders characterized by iron accumulation in the basal ganglia. Recently, mutations in CoA synthase (COASY) have been identified as a cause of a novel NBIA subtype (COASY Protein-Associated Neurodegeneration, CoPAN) in two patients with dystonic paraparesis, parkinsonian features, cognitive impairment, behavior abnormalities, and axonal neuropathy. COASY encodes an enzyme required for Coenzyme A (CoA) biosynthesis. Using whole exome sequencing (WES) we identified compound heterozygous COASY mutations in two siblings with intellectual disability, ataxic gait, progressive spasticity, and obsessive-compulsive behavior...
May 10, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28485685/protein-palmitoylation-palmitoyltransferases-and-their-specificity
#16
Sabina Tabaczar, Aleksander Czogalla, Joanna Podkalicka, Agnieszka Biernatowska, Aleksander F Sikorski
A plethora of novel information has emerged over the past decade regarding protein lipidation. The reversible attachment of palmitic acid to cysteine residues, termed S-palmitoylation, has focused a special attention. This is mainly due to the unique role of this modification in the regulation of protein trafficking and function. A large family of protein acyltransferases (PATs) containing a conserved aspartate-histidine-histidine-cysteine motif use ping-pong kinetic mechanism to catalyze S-palmitoylation of a substrate protein...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28484221/a-novel-non-genomic-glucocorticoid-signaling-mediated-by-a-membrane-palmitoylated-glucocorticoid-receptor-cross-talks-with-gnrh-in-gonadotrope-cells
#17
Mohsen Ayrout, Violaine Simon, Valérie Bernard, Nadine Binart, Joëlle Cohen-Tannoudji, Marc Lombès, Stéphanie Chauvin
Glucocorticoid hormones (GC) are the main stress mediators associated with reproductive disorders. GC exert their effects through activation of the glucocorticoid receptor (GR) principally acting as a transcription factor. Beside well-established GR-mediated genomic actions, several lines of evidence suggest a role for rapid membrane-initiated GC signaling in gonadotrope cells triggered by a membrane-associated GR. Herein, we demonstrate the existence of a specific membrane-initiated GC signaling in LβT2 gonadotrope cells involving two related phosphoproteins: Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) and synapsin-I...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28482659/position-dependent-diffusion-tensors-in-anisotropic-media-from-simulation-oxygen-transport-in-and-through-membranes
#18
An Ghysels, Richard M Venable, Richard Walter Pastor, Gerhard Hummer
A Bayesian-based methodology is developed to estimate diffusion tensors from molecular dynamics simulations of permeants in anisotropic media, and is applied to oxygen in lipid bilayers. By a separation of variables in the Smoluchowski diffusion equation, the multidimensional diffusion is reduced to coupled one-dimensional diffusion problems that are treated by discretization. The resulting diffusivity profiles characterize the membrane transport dynamics as a function of the position across the membrane, discriminating between diffusion normal and parallel to the membrane...
May 8, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28476891/drosophila-tg-a-transglutaminase-is-secreted-via-an-unconventional-golgi-independent-mechanism-involving-exosomes-and-two-types-of-fatty-acylations
#19
Toshio Shibata, Jinki Hadano, Daichi Kawasaki, Xiaoqing Dong, Shun-Ichiro Kawabata
Transglutaminases (TGs) play essential intracellular and extracellular roles by covalently cross-linking many proteins. Drosophila TG is encoded by one gene and has two alternative splicing-derived isoforms, TG-A and TG-B, which contain distinct N-terminal 46- and 38-amino acid sequences, respectively. The TGs identified to date do not have a typical endoplasmic reticulum (ER)-signal peptide, and the molecular mechanisms of their secretion under physiologic conditions are unclear. Immunocytochemistry revealed that TG-A localizes to multivesicular-like structures, whereas TG-B localizes to the cytosol...
May 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28476091/how-a-short-pore-forming-peptide-spans-the-lipid-membrane
#20
Mikkel Vestergaard, Mikkel Christensen, Sara K Hansen, Dennis Grønvall, Lisbeth R Kjølbye, Thomas Vosegaard, Birgit Schiøtt
Many antimicrobial peptides function by forming pores in the plasma membrane of the target cells. Intriguingly, some of these peptides are very short, and thus, it is not known how they can span the membrane, or whether other mechanisms of cell disruption are dominant. Here, the conformation and orientation of the 14-residue peptaibol SPF-5506-A4 (SPF) are investigated in lipid environments by atomistic and coarse grained molecular dynamics (MD) simulations, circular dichroism, and nuclear magnetic resonance (NMR) experiments...
May 5, 2017: Biointerphases
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