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https://www.readbyqxmd.com/read/28808998/microfluidics-mass-spectrometry-of-protein-carbohydrate-interactions-applications-to-the-development-of-therapeutics-and-biomarker-discovery
#1
Alina D Zamfir
The functional interactions of carbohydrates and their protein receptors are the basis of biological events critical to the evolution of pathological states. Hence, for the past years, such interactions have become the focus of research for the development of therapeutics and discovery of novel glycan biomarkers based on their binding affinity. Due to the high sensitivity, throughput, reproducibility, and capability to ionize minor species in heterogeneous mixtures, microfluidics-mass spectrometry (MS) has recently emerged as a method of choice in protein-glycan interactomics...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808666/lipidomic-evaluation-of-feline-neurologic-disease-after-aav-gene-therapy
#2
Heather L Gray-Edwards, Xuntian Jiang, Ashley N Randle, Amanda R Taylor, Taylor L Voss, Aime K Johnson, Victoria J McCurdy, Miguel Sena-Esteves, Daniel S Ory, Douglas R Martin
GM1 gangliosidosis is a fatal lysosomal disorder, for which there is no effective treatment. Adeno-associated virus (AAV) gene therapy in GM1 cats has resulted in a greater than 6-fold increase in lifespan, with many cats remaining alive at >5.7 years of age, with minimal clinical signs. Glycolipids are the principal storage product in GM1 gangliosidosis whose pathogenic mechanism is not completely understood. Targeted lipidomics analysis was performed to better define disease mechanisms and identify markers of disease progression for upcoming clinical trials in humans...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28805811/caveolin-1-dependent-nanoscale-organization-of-the-bcr-regulates-b-cell-tolerance
#3
Susana Minguet, Kathrin Kläsener, Anna-Maria Schaffer, Gina J Fiala, Teresa Osteso-Ibánez, Katrin Raute, Inmaculada Navarro-Lérida, Frederike A Hartl, Maximilian Seidl, Michael Reth, Miguel A Del Pozo
Caveolin-1 (Cav1) regulates the nanoscale organization and compartmentalization of the plasma membrane. Here we found that Cav1 controlled the distribution of nanoclusters of isotype-specific B cell antigen receptors (BCRs) on the surface of B cells. In mature B cells stimulated with antigen, the immunoglobulin M BCR (IgM-BCR) gained access to lipid domains enriched for GM1 glycolipids, by a process that was dependent on the phosphorylation of Cav1 by the Src family of kinases. Antigen-induced reorganization of nanoclusters of IgM-BCRs and IgD-BCRs regulated BCR signaling in vivo...
August 14, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28796418/role-of-the-gm1-ganglioside-oligosaccharide-portion-in-the-trka-dependent-neurite-sprouting-in-neuroblastoma-cells
#4
Elena Chiricozzi, Diego Yuri Pomè, Margherita Maggioni, Erika Di Biase, Chiara Parravicini, Luca Palazzolo, Nicoletta Loberto, Ivano Eberini, Sandro Sonnino
GM1 ganglioside (II(3) NeuAc-Gg4 Cer) is known to promote neurite formation in neuroblastoma cells by activating TrkA-MAPK pathway. The molecular mechanism by which GM1 is involved in the neurodifferentiation process is still unknown, however, in vitro and in vivo evidences have suggested that the oligosaccharide portion of this ganglioside could be involved. Here, we report that, similarly to the entire GM1 molecule, its oligosaccharide II(3) NeuAc-Gg4, rather than its ceramide (Cer) portion is responsible for the neurodifferentiation process by augmenting neurite elongation and increasing the neurofilament protein expression in murine neuroblastoma cells, Neuro2a...
August 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28768095/investigating-the-influence-of-membrane-composition-on-protein-glycolipid-binding-using-nanodiscs-and-proxy-ligand-electrospray-ionization-mass-spectrometry
#5
Ling Han, Luis C Morales, Michele R Richards, Elena N Kitova, Simonetta Sipione, John S Klassen
This work describes a versatile analytical approach, which combines the proxy ligand electrospray ionization mass spectrometry (ESI-MS) assay and model membranes of defined composition, to quantify the influence of lipid bilayer composition on protein-glycolipid binding in vitro. To illustrate the implementation of the assay (experimental design and data analysis), affinities of the monosialoganglioside ligand GM1, incorporated into nanodiscs (NDs), for cholera toxin B subunit homopentamer (CTB5) were measured...
August 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28761428/monosialoganglioside-1-may-alleviate-neurotoxicity-induced-by-propofol-combined-with-remifentanil-in-neural-stem-cells
#6
Jiang Lu, Xue-Qin Yao, Xin Luo, Yu Wang, Sookja Kim Chung, He-Xin Tang, Chi Wai Cheung, Xian-Yu Wang, Chen Meng, Qing Li
Monosialoganglioside 1 (GM1) is the main ganglioside subtype and has neuroprotective properties in the central nervous system. In this study, we aimed to determine whether GM1 alleviates neurotoxicity induced by moderate and high concentrations of propofol combined with remifentanil in the immature central nervous system. Hippocampal neural stem cells were isolated from newborn Sprague-Dawley rats and treated with remifentanil (5, 10, 20 ng/mL) and propofol (1.0, 2.5, 5.0 μg/mL), and/or GM1 (12.5, 25, 50 μg/mL)...
June 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28749998/lc-ms-ms-multiplex-analysis-of-lysosphingolipids-in-plasma-and-amniotic-fluid-a-novel-tool-for-the-screening-of-sphingolipidoses-and-niemann-pick-type-c-disease
#7
Magali Pettazzoni, Roseline Froissart, Cécile Pagan, Marie T Vanier, Séverine Ruet, Philippe Latour, Nathalie Guffon, Alain Fouilhoux, Dominique P Germain, Thierry Levade, Christine Vianey-Saban, Monique Piraud, David Cheillan
BACKGROUND: The biological diagnosis of sphingolipidoses currently relies on the measurement of specific enzymatic activities and/or genetic studies. Lysosphingolipids have recently emerged as potential biomarkers of sphingolipidoses and Niemann-Pick type C in plasma. METHODOLOGY: We developed a sensitive and specific method enabling the simultaneous quantification of lysosphingolipids by LC-MS/MS: lysoglobotriaosylceramide for Fabry disease, lysohexosylceramide (i...
2017: PloS One
https://www.readbyqxmd.com/read/28744122/penetration-of-blood-brain-barrier-and-antitumor-activity-and-nerve-repair-in-glioma-by-doxorubicin-loaded-monosialoganglioside-micelles-system
#8
Dan Zou, Wei Wang, Daoxi Lei, Ying Yin, Peng Ren, Jinju Chen, Tieying Yin, Bochu Wang, Guixue Wang, Yazhou Wang
For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28736286/lack-of-immunotoxic-effects-of-repeated-exposure-to-atrazine-associated-with-the-adaptation-of-adrenal-gland-activation
#9
Chad D Foradori, Arthur D Zimmerman, Pragati S Coder, Vanessa L Peachee, Robert J Handa, Ian Kimber, Stephen B Pruett, Charles B Breckenridge
T cell-dependent IgM antibody production and natural killer cell (NKC) activity were assessed in SD rats orally administered atrazine for 28 days to males (0, 6.5, 25, or 100 mg/kg/day) or females (0, 3, 6, or 50 mg/kg/day), or 30 or 500 ppm in diet (3 or 51 mg/kg/day). Anti-asialo GM1 antibodies (NKC) and cyclophosphamide (antibody-forming cell assay [AFC]) served as positive controls. Pituitary (ACTH, prolactin), adrenal (corticosterone, progesterone, aldosterone), and gonadal (androgens, estrogens) hormones were assessed after 1, 7, and/or 28 days of treatment...
July 20, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28734966/development-of-new-ganglioside-probes-and-unraveling-of-raft-domain-structure-by-single-molecule-imaging
#10
REVIEW
Kenichi G N Suzuki, Hiromune Ando, Naoko Komura, Takahiro Fujiwara, Makoto Kiso, Akihiro Kusumi
Gangliosides are involved in a variety of biological roles and are a component of lipid rafts found in cell plasma membranes (PMs). Gangliosides are especially abundant in neuronal PMs and are essential to their physiological functions. However, the dynamic behaviors of gangliosides have not been investigated in living cells due to a lack of fluorescent probes that behave like their parental molecules. We have recently developed, using an entirely chemical method, four new ganglioside probes (GM1, GM2, GM3, and GD1b) that act similarly to their parental molecules in terms of raft partitioning and binding affinity...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28716012/case-reports-of-juvenile-gm1-gangliosidosisis-type-ii-caused-by-mutation-in-glb1-gene
#11
Parvaneh Karimzadeh, Samaneh Naderi, Farzaneh Modarresi, Hassan Dastsooz, Hamid Nemati, Tayebeh Farokhashtiani, Bibi Shahin Shamsian, Soroor Inaloo, Mohammad Ali Faghihi
BACKGROUND: Type II or juvenile GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder, which is clinically distinct from infantile form of the disease by the lack of characteristic cherry-red spot and hepatosplenomegaly. The disease is characterized by slowly progressive neurodegeneration and mild skeletal changes. Due to the later age of onset and uncharacteristic presentation, diagnosis is frequently puzzled with other ataxic and purely neurological disorders. Up to now, 3-4 types of GM1-gangliosidosis have been reported and among them type I is the most common phenotype with the age of onset around 6 months...
July 17, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28686720/free-cholesterol-and-cholesterol-esters-in-bovine-oocytes-implications-in-survival-and-membrane-raft-organization-after-cryopreservation
#12
Jorgelina Buschiazzo, Glenda L Ríos, Jesica R Canizo, Silvia S Antollini, Ricardo H Alberio
Part of the damage caused by cryopreservation of mammalian oocytes occurs at the plasma membrane. The addition of cholesterol to cell membranes as a strategy to make it more tolerant to cryopreservation has been little addressed in oocytes. In order to increase the survival of bovine oocytes after cryopreservation, we proposed not only to increase cholesterol level of oocyte membranes before vitrification but also to remove the added cholesterol after warming, thus recovering its original level. Results from our study showed that modulation of membrane cholesterol by methyl-β-cyclodextrin (MβCD) did not affect the apoptotic status of oocytes and improved viability after vitrification yielding levels of apoptosis closer to those of fresh oocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28674340/aromaticity-of-phenylalanine-residues-is-essential-for-amyloid-formation-by-alzheimer-s-amyloid-%C3%AE-peptide
#13
Mayumi Genji, Yoshiaki Yano, Masaru Hoshino, Katsumi Matsuzaki
The abnormal aggregation of amyloid β-peptide (Aβ) is central to the pathogenesis of Alzheimer's disease, the major form of dementia. Aromatic π-π interactions have been suggested to play a crucial role in the aggregation of not only Aβ, but also other amyloidogenic proteins. In this study, each or all phenylalanine (Phe) residues at the 4th, 19th, and 20th positions of Aβ-(1-40) were substituted by hydrophobic cyclohexylalanine (Cha), which is sterically similar to Phe, but lacks π-electrons, to reveal effects of interactions involving π-electrons on the aggregation of Aβ both in aqueous solution and GM1-containing membranes...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28673733/enhanced-soluble-production-of-cholera-toxin-b-subunit-in-escherichia-coli-by-co-expression-of-skp-chaperones
#14
Yuanpeng Zhang, Xuwen Qiao, Xiaoming Yu, Jin Chen, Liting Hou, Zhixiang Bi, Qisheng Zheng, Jibo Hou
The cholera toxin B subunit (CTB) is a nontoxic portion of the cholera toxin that retains mucosal adjuvant properties. Expression of CTB in Escherichia coli is difficult as CTB aggregates and accumulates as insoluble inclusion bodies. To remedy this problem, the periplasmic chaperone, SKP, was investigated as possible co-expression partner to increase the solubility of recombinant CTB (rCTB) in E. coli. The result showed co-expression of SKP enhanced the soluble expression of rCTB in E. coli. Moreover, soluble rCTB was successfully expressed and secreted into the periplasmic space through the direction of the LTB leader signal...
October 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28660589/on-electrochemical-methods-for-determination-of-protein-lipid-interaction
#15
Zhiping Hu, Yanli Mao
Amyloid-β (Aβ) peptides are important and reliable molecular biomarkers for the diagnosis and prognosis of Alzheimer's disease. Aggregation and fibrillization of Aβ peptides on ganglioside GM1 (GM1)-containing lipid membranes is considered a cause of neurodegenerative disease. Because GM1 is abundant in the central nervous system and plays a key role in the aggregation of Aβ, the interaction of Aβ with supported planar lipid bilayers (SPBs) containing GM1 is of great significance. We have prepared SPBs containing GM1 in order to study the electrochemical characteristics of GM1/sphingomyelin/cholesterol SPBs and their interaction with Aβ(1-40) by cyclic voltammetry and electrochemical impedance spectroscopy (EIS), which proves that electrochemical is a promising method for analyzing the interaction between peptides and lipid membranes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28656734/simvastatin-induced-actin-cytoskeleton-disassembly-in-normal-and-transformed-fibroblasts-without-affecting-lipid-raft-integrity
#16
Vladislav I Chubinskiy-Nadezhdin, Yuri A Negulyaev, Elena A Morachevskaya
Statins are the most commonly prescribed agents used to modulate cholesterol levels in course of hypercholesterolemia treatment because of their relative tolerability and LDL-C lowering effect. Recently, there are emerging interests in the perspectives of statin drugs as anticancer agents based on preclinical evidence of their antiproliferative, proapoptotic, and anti-invasive properties. Functional impact of statin application on transformed cells still remains obscure that requires systematic study on adequate cellular models to provide correct comparison with their non-transformed counterparts...
June 28, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28651685/erratum-to-ganglioside-gm1-influences-the-proliferation-rate-of-mouse-induced-pluripotent-stem-cells
#17
Jae-Sung Ryu, Kyu-Tae Chang, Ju-Taek Lee, Malg-Um Lim, Hyun-Ki Min, Yoon-Ju Na, Su-Bin Lee, Gislain Moussavou, Sun-Uk Kim, Ji-Su Kim, Kinarm Ko, Kisung Ko, Kyung-A Hwang, Eun-Jeong Jeong, Jeong-Woong Lee, Young-Kug Choo
The BMB Reports would like to correct in the ACKNOWLEDGEMENTS of BMB Rep. 45(12), 713-718 titled "Ganglioside GM1 influences the proliferation rate of mouse induced pluripotent stem cells".
June 2017: BMB Reports
https://www.readbyqxmd.com/read/28628327/impact-of-the-niemann-pick-c1-gene-mutation-on-the-total-cellular-glycomics-of-cho-cells
#18
Jun-Ichi Furukawa, Minami Soga, Kazue Okada, Ikuko Yokota, Jinhua Piao, Tetsumi Irie, Takumi Era, Yasuro Shinohara
Niemann-Pick disease type C (NPC) is an autosomal recessive lipid storage disorder, and the majority of cases are caused by mutations in the NPC1 gene. In this study, we clarified how a single gene mutation in the NPC1 gene impacts the cellular glycome by analyzing the total glycomic expression profile of Chinese hamster ovary cell mutants defective in the Npc1 gene (Npc1 KO CHO cells). A number of glycomic alterations were identified, including increased expression of lactosylceramide, GM1, GM2, GD1, various neolacto-series glycosphingolipids, and sialyl-T (O-glycan), which was found to be the major sialylated protein-bound glycan, as well as various N-glycans, which were commonly both fucosylated and sialylated...
July 3, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28600215/a-new-type-of-pharmacological-chaperone-for-gm1-gangliosidosis-related-human-lysosomal-%C3%AE-galactosidase-n-substituted-5-amino-1-hydroxymethyl-cyclopentanetriols
#19
Michael Schalli, Patrick Weber, Christina Tysoe, Bettina M Pabst, Martin Thonhofer, Eduard Paschke, Arnold E Stütz, Marion Tschernutter, Werner Windischhofer, Stephen G Withers
N-Functionalized amino(hydroxymethyl)cyclopentanetriols are potent inhibitors of β-d-galactosidases and, for the first time, could be shown to act as pharmacological chaperones for GM1-gangliosidosis-associated lysosomal acid β-galactosidase thus representing a new structural type of pharmacological chaperones for this lysosomal storage disease.
August 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28593141/glycosyl-chains-and-25-hydroxycholesterol-contribute-to-the-intracellular-transport-of-amyloid-beta-a%C3%AE-42-in-jurkat-t-cells
#20
Neha Sharma, KeangOK Baek, Huong T T Phan, Naofumi Shimokawa, Masahiro Takagi
Amyloid beta (Aβ) is a peptide responsible for the development of Alzheimer's disease (AD). Misfolding and accumulation of endogenous Aβ can lead to neural cell apoptosis through endoplasmic reticulum (ER) stress. Added exogenous Aβ can also result in ER stress, leading to neurotoxicity and apoptosis, which is identical to that caused by the endogenous peptide. We have speculated that the endocytic transport of Aβ causes ER stress and have previously shown that the oxysterol, in particular, 7-ketocholesterol (7-keto) induces more surface interaction between Aβ-42 and Jurkat cells than cholesterol...
June 2017: FEBS Open Bio
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