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Lipid membrane disease

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https://www.readbyqxmd.com/read/28096355/a-natural-product-inhibits-the-initiation-of-%C3%AE-synuclein-aggregation-and-suppresses-its-toxicity
#1
Michele Perni, Céline Galvagnion, Alexander Maltsev, Georg Meisl, Martin B D Müller, Pavan K Challa, Julius B Kirkegaard, Patrick Flagmeier, Samuel I A Cohen, Roberta Cascella, Serene W Chen, Ryan Limboker, Pietro Sormanni, Gabriella T Heller, Francesco A Aprile, Nunilo Cremades, Cristina Cecchi, Fabrizio Chiti, Ellen A A Nollen, Tuomas P J Knowles, Michele Vendruscolo, Adriaan Bax, Michael Zasloff, Christopher M Dobson
The self-assembly of α-synuclein is closely associated with Parkinson's disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects α-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces α-synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28092368/molecular-insights-into-lipid-assisted-ca-2-regulation-of-the-trp-channel-polycystin-2
#2
Martin Wilkes, M Gregor Madej, Lydia Kreuter, Daniel Rhinow, Veronika Heinz, Silvia De Sanctis, Sabine Ruppel, Rebecca M Richter, Friederike Joos, Marina Grieben, Ashley C W Pike, Juha T Huiskonen, Elisabeth P Carpenter, Werner Kühlbrandt, Ralph Witzgall, Christine Ziegler
Polycystin-2 (PC2), a calcium-activated cation TRP channel, is involved in diverse Ca(2+) signaling pathways. Malfunctioning Ca(2+) regulation in PC2 causes autosomal-dominant polycystic kidney disease. Here we report two cryo-EM structures of distinct channel states of full-length human PC2 in complex with lipids and cations. The structures reveal conformational differences in the selectivity filter and in the large exoplasmic domain (TOP domain), which displays differing N-glycosylation. The more open structure has one cation bound below the selectivity filter (single-ion mode, PC2SI), whereas multiple cations are bound along the translocation pathway in the second structure (multi-ion mode, PC2MI)...
January 16, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28091625/mplex-a-method-for-simultaneous-pathogen-inactivation-and-extraction-of-samples-for-multi-omics-profiling
#3
Kristin E Burnum-Johnson, Jennifer E Kyle, Amie J Eisfeld, Cameron P Casey, Kelly G Stratton, Juan F Gonzalez, Fabien Habyarimana, Nicholas M Negretti, Amy C Sims, Sadhana Chauhan, Larissa B Thackray, Peter J Halfmann, Kevin B Walters, Young-Mo Kim, Erika M Zink, Carrie D Nicora, Karl K Weitz, Bobbie-Jo M Webb-Robertson, Ernesto S Nakayasu, Brian Ahmer, Michael E Konkel, Vladimir Motin, Ralph S Baric, Michael S Diamond, Yoshihiro Kawaoka, Katrina M Waters, Richard D Smith, Thomas O Metz
The continued emergence and spread of infectious agents is of great concern, and systems biology approaches to infectious disease research can advance our understanding of host-pathogen relationships and facilitate the development of new therapies and vaccines. Molecular characterization of infectious samples outside of appropriate biosafety containment can take place only subsequent to pathogen inactivation. Herein, we describe a modified Folch extraction using chloroform/methanol that facilitates the molecular characterization of infectious samples by enabling simultaneous pathogen inactivation and extraction of proteins, metabolites, and lipids for subsequent mass spectrometry-based multi-omics measurements...
January 16, 2017: Analyst
https://www.readbyqxmd.com/read/28088624/oxidative-phospholipidomics-in-health-and-disease-achievements-challenges-and-hopes
#4
REVIEW
Ana Reis
Phospholipid peroxidation products are recognized as important bioactive lipid mediators playing an active role as modulators in signalling events in inflammation, immunity and infection. The biochemical responses are determined by the oxidation structural features present in oxPL modulating biophysical and biological properties in model membranes and lipoproteins. In spite of the extensive work conducted with model systems over the last 20 years, the study of oxPL in biological systems has virtually stagnated...
January 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28088576/lid-domain-plasticity-and-lipid-flexibility-modulate-enzyme-specificity-in-human-monoacylglycerol-lipase
#5
Laura Riccardi, Jose M Arencibia, Luca Bono, Andrea Armirotti, Stefania Girotto, Marco De Vivo
Human monoacylglycerol lipase (MAGL) is a membrane-interacting enzyme that generates pro-inflammatory signaling molecules. For this reason, MAGL inhibition is a promising strategy to treat pain, cancer, and neuroinflammatory diseases. MAGL can hydrolyze monoacylglycerols bearing an acyl chain of different lengths and degrees of unsaturation, cleaving primarily the endocannabinoid 2-arachidonoylglycerol. Importantly, the enzymatic binding site of MAGL is confined by a 75-amino-acid-long, flexible cap domain, named 'lid domain', which is structurally similar to that found in several other lipases...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28080049/modeling-diversity-in-structures-of-bacterial-outer-membrane-lipids
#6
Huilin Ma, Daniel D Cummins, Natalie Brooke Edelstein, Jerry Gomez, Aliza Khan, Masud Dikita Llewellyn, Tara Picudella, Sarah Rose Willsey, Shikha Nangia
Lipopolysaccharides are vital components of the outer membrane of gram-negative bacteria, and they act as extremely strong stimulators of innate immunity in diverse eukaryotic species. The primary immunostimulatory center of the LPS molecule is lipid A-a disaccharide-bound lipophilic domain. Considering the broad diversity in bacterial species, there are variations in the lipid A structure and their immunogenic potency. In this work, we model the lipid A structures of eight commensal or human pathogenic bacterial species: Helicobacter pylori, Porphyromonas gingivalis, Bacteroides fragilis, Bordetella pertussis, Chlamydia trachomatis, Campylobacter jejuni, Neisseria meningitidis, and Salmonella minnesota...
January 12, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28079896/impaired-embryonic-development-in-glucose-6-phosphate-dehydrogenase-deficient-caenorhabditis-elegans-due-to-abnormal-redox-homeostasis-induced-activation-of-calcium-independent-phospholipase-and-alteration-of-glycerophospholipid-metabolism
#7
Tzu-Ling Chen, Hung-Chi Yang, Cheng-Yu Hung, Meng-Hsin Ou, Yi-Yun Pan, Mei-Ling Cheng, Arnold Stern, Szecheng J Lo, Daniel Tsun-Yee Chiu
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly pervasive inherited disease in many parts of the world. The complete lack of G6PD activity in a mouse model causes embryonic lethality. The G6PD-deficient Caenorhabditis elegans model also shows embryonic death as indicated by a severe hatching defect. Although increased oxidative stress has been implicated in both cases as the underlying cause, the exact mechanism has not been clearly delineated. In this study with C. elegans, membrane-associated defects, including enhanced permeability, defective polarity and cytokinesis, were found in G6PD-deficient embryos...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28077646/adenovirus-modulates-toll-like-receptor-4-signaling-by-reprogramming-orp1l-vap-protein-contacts-for-cholesterol-transport-from-endosomes-to-the-endoplasmic-reticulum
#8
Nicholas L Cianciola, Stacey Chung, Danny Manor, Cathleen R Carlin
: Human adenoviruses generally cause mild self-limiting infections but can lead to serious disease and even be fatal in high-risk individuals, underscoring the importance of understanding how the virus counteracts host defense mechanisms. This study had two goals. First, determine the molecular basis of cholesterol homeostatic responses induced by the early region 3 membrane protein RIDα via its direct interaction with the sterol-binding protein ORP1L. Second, determine how this interaction regulates innate immunity to adenovirus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28075131/classical-galactosemia-insight-into-molecular-pathomechanisms-by-differential-membrane-proteomics-of-fibroblasts-under-galactose-stress
#9
Simon Staubach, Stefan Müller, Murat Pekmez, Franz-Georg Hanisch
Classical galactosemia, a hereditary metabolic disease caused by the deficiency of galactose-1-phosphate uridyltransferase (GALT; EC 2.7.712), results in an impaired galactose metabolism and serious long-term developmental affection of the CNS and ovaries, potentially related in part to endogenous galactose-induced protein dysglycosylation. In search for galactose-induced changes in membrane raft proteomes of GALT-deficient cells, we performed differential analyses of lipid rafts from patient-derived (Q) and sex- and age-matched control fibroblasts (H) in the presence or absence of the stressor...
January 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28073164/protective-role-of-endogenous-plasmalogens-against-hepatic-steatosis-and-steatohepatitis
#10
Jung Eun Jang, Han-Sol Park, Hyun Ju Yoo, In-Jeoung Baek, Ji Eun Yoon, Myoung Seok Ko, Ah-Ram Kim, Hyoun Sik Kim, Hye-Sun Park, Seung Eun Lee, Seung-Whan Kim, Su Jung Kim, Jaechan Leem, Yu Mi Kang, Min Kyo Jung, Chan-Gi Pack, Chong Jai Kim, Chang Ohk Sung, In-Kyu Lee, Joong-Yeol Park, José C Fernández-Checa, Eun Hee Koh, Ki-Up Lee
: Free cholesterol (FC) accumulation in the liver is an important pathogenic mechanism of nonalcoholic steatohepatitis (NASH). Plasmalogens, key structural components of the cell membrane, act as endogenous antioxidants and are primarily synthesized in the liver. However, the role of hepatic plasmalogens in metabolic liver disease is unclear. In this study, we found that hepatic levels of docosahexaenoic acid (DHA)-containing plasmalogens, expression of glyceronephosphate O-acyltransferase (Gnpat, the rate-limiting enzyme in plasmalogen biosynthesis), and expression of Pparα were lower in mice with NASH caused by accumulation of free cholesterol (FC) in the liver...
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28072421/on-the-ecosystemic-network-of-saliva-in-healthy-young-adults
#11
Egija Zaura, Bernd W Brandt, Andrei Prodan, Maarten Joost Teixeira de Mattos, Sultan Imangaliyev, Jolanda Kool, Mark J Buijs, Ferry Lpw Jagers, Nienke L Hennequin-Hoenderdos, Dagmar E Slot, Elena A Nicu, Maxim D Lagerweij, Marleen M Janus, Marcela M Fernandez-Gutierrez, Evgeni Levin, Bastiaan P Krom, Henk S Brand, Enno Ci Veerman, Michiel Kleerebezem, Bruno G Loos, G A van der Weijden, Wim Crielaard, Bart Jf Keijser
A dysbiotic state is believed to be a key factor in the onset of oral disease. Although oral diseases have been studied for decades, our understanding of oral health, the boundaries of a healthy oral ecosystem and ecological shift toward dysbiosis is still limited. Here, we present the ecobiological heterogeneity of the salivary ecosystem and relations between the salivary microbiome, salivary metabolome and host-related biochemical salivary parameters in 268 healthy adults after overnight fasting. Gender-specific differences in the microbiome and metabolome were observed and were associated with salivary pH and dietary protein intake...
January 10, 2017: ISME Journal
https://www.readbyqxmd.com/read/28071002/effect-of-antioxidants-on-polyunsaturated-fatty-acids-review
#12
Ancuţa Elena Prisacaru
This paper aims to review the available literature data and provide an overview regarding the efficiency of antioxidants to prevent peroxidation of polyunsaturated fatty acids. Lipid peroxidation is a serious problem that often leads to a loss of shelf-life, reduced consumer acceptability, poorer functionality, lower nutritional value, and poorer safety. It represents an oxidative degradation of polyunsaturated fatty acids incorporated in cell membrane lipids or in lipoproteins, but also in vegetables and food oils rich in PUFA n-3...
April 2016: Acta Scientiarum Polonorum. Technologia Alimentaria
https://www.readbyqxmd.com/read/28069058/endosulfine-alpha-inhibits-membrane-induced-%C3%AE-synuclein-aggregation-and-protects-against-%C3%AE-synuclein-neurotoxicity
#13
Daniel Ysselstein, Benjamin Dehay, Isabel M Costantino, George P McCabe, Matthew P Frosch, Julia M George, Erwan Bezard, Jean-Christophe Rochet
Neuropathological and genetic findings suggest that the presynaptic protein α-synuclein (aSyn) is involved in the pathogenesis of synucleinopathy disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy. Evidence suggests that the self-assembly of aSyn conformers bound to phospholipid membranes in an aggregation-prone state plays a key role in aSyn neurotoxicity. Accordingly, we hypothesized that protein binding partners of lipid-associated aSyn could inhibit the formation of toxic aSyn oligomers at membrane surfaces...
January 10, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28068633/polyphenol-rich-ethanolic-extract-from-boerhavia-diffusa-l-mitigates-angiotensin-ii-induced-cardiac-hypertrophy-and-fibrosis-in-rats
#14
Prathapan A, Mathews V Varghese, Abhilash S, Salin Raj P, Anil K Mathew, Anupama Nair, R Harikumaran Nair, Raghu K G
Boerhavia diffusa is a renowned edible medicinal plant extensively used against different ailments including heart diseases in the traditional system of medicine in several countries. The present study aims to evaluate the therapeutic efficacy of ethanolic extract of Boerhavia diffusa (BDE) on cardiac hypertrophy and fibrosis induced by angiotensin II (Ang II) in male wistar rats and to identify the active components present in it. A substantial increase of hypertrophy markers such as cardiac mass index, concentration of ANP and BNP, cardiac injury markers like CK-MB, LDH and SGOT, has been observed in hypertrophied groups whereas BDE treatment attenuated these changes when compared to hypertrophied rats...
January 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28065269/methods-for-structural-and-functional-analyses-of-intramembrane-prenyltransferases-in-the-ubia-superfamily
#15
Y Yang, N Ke, S Liu, W Li
The UbiA superfamily is a group of intramembrane prenyltransferases that generate lipophilic compounds essential in biological membranes. These compounds, which include various quinones, hemes, chlorophylls, and vitamin E, participate in electron transport and function as antioxidants, as well as acting as structural lipids of microbial cell walls and membranes. Prenyltransferases producing these compounds are involved in important physiological processes and human diseases. These UbiA superfamily members differ significantly in their enzymatic activities and substrate selectivities...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28065268/enzymatic-assays-for-studying-intramembrane-proteolysis
#16
D M Bolduc, D J Selkoe, M S Wolfe
Proteolysis within the membrane is catalyzed by a diverse family of proteases immersed within the hydrophobic environment of cellular membranes. These ubiquitous intramembrane-cleaving proteases (I-CLiPs) hydrolyze the transmembrane domains of a large variety of membrane-embedded proteins to facilitate signaling events essential to normal biological functions found in all forms of life. The importance of this unique class of enzyme is highlighted by its central involvement in a variety of human pathologies, including Alzheimer's disease (AD), Parkinson's disease, cancer, and the virulence of a number of viral, bacterial, and fungal pathogens...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28065266/production-of-recombinant-rhomboid-proteases
#17
E Arutyunova, R Panigrahi, K Strisovsky, M J Lemieux
Rhomboid proteases are intramembrane enzymes that hydrolyze peptide bonds of transmembrane proteins in the lipid bilayer. They play a variety of roles in key biological events and are linked to several disease states. Over the last decade a great deal of structural and functional knowledge has been generated on this fascinating class of proteases. Both structural and kinetic analyses require milligram amounts of protein, which may be challenging for membrane proteins such as rhomboids. Here, we present a detailed protocol for optimization of expression and purification of three rhomboid proteases from Escherichia coli (ecGlpG), Haemophilus influenzae (hiGlpG), and Providencia stuartii (AarA)...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28065261/expression-purification-and-enzymatic-characterization-of-intramembrane-proteases
#18
R Zhou, Y Shi, G Yang
Intramembrane proteases catalyze peptide bond hydrolysis in the lipid bilayer and play a key role in numerous cellular processes. These integral membrane enzymes consist of four classes: site-2 protease (S2P), rhomboid serine protease, Rce1-type glutamyl protease, and aspartyl protease exemplified by presenilin and signal peptide peptidase (SPP). Structural elucidation of these enzymes is important for mechanistic understanding of their functions, particularly their roles in cell signaling and debilitating diseases such as Parkinson's disease and Alzheimer's disease...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28063500/cellular-assays-for-evaluating-calcium-dependent-translocation-of-cpla2%C3%AE-to-membrane
#19
B Yun, C C Leslie
The group IVA phospholipase A2, commonly called cytosolic phospholipase A2α (cPLA2α), is a widely expressed enzyme that hydrolyzes membrane phospholipid to produce arachidonic acid and lysophospholipids, which are precursors for a number of bioactive lipid mediators. Arachidonic acid is metabolized through the cyclooxygenase and lipoxygenase pathways for production of prostaglandins and leukotrienes that regulate normal physiological processes and contribute to disease pathogenesis. cPLA2α is composed of an N-terminal C2 domain and a C-terminal catalytic domain that contains the Ser-Asp catalytic dyad...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28062666/cyclodextrin-has-conflicting-actions-on-autophagy-flux-in-vivo-in-brains-of-normal-and-alzheimer-model-mice
#20
Dun-Sheng Yang, Philip Stavrides, Asok Kumar, Ying Jiang, Panaiyur S Mohan, Masuo Ohno, Kostantin Dobrenis, Cristin D Davidson, Mitsuo Saito, Monika Pawlik, Chunfeng Huo, Steven U Walkley, Ralph A Nixon
2-hydroxypropyl-β-cyclodextrin (CYCLO), a modifier of cholesterol efflux from cellular membrane and endo-lysosomal compartments, reduces lysosomal lipid accumulations and has therapeutic effects in animal models of Niemann-Pick disease type C and several other neurodegenerative states. Here, we investigated CYCLO effects on autophagy in wild-type mice and TgCRND8 mice - an Alzheimer's Disease (AD) model exhibiting β-amyloidosis, neuronal autophagy deficits leading to protein and lipid accumulation within greatly enlarged autolysosomes...
January 5, 2017: Human Molecular Genetics
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