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Majid Vahed, Saburo Neya, Katsumi Matsuzaki, Tyuji Hoshino
The interaction of amyloid beta (Aβ) peptide with cell membrane is one of the factors enhancing Aβ aggregation, which is closely related to neuro-disturbance disease. In this work, we performed molecular dynamics (MD) simulation to investigate the initial stage of adhesion of Aβ40 to a GM1 ganglioside-containing membrane. Conformational change of Aβ40 due to interaction with the membrane was monitored and compared with that of Aβ42 observed in the previous study. Multiple computational trials were executed to analyze the probability of Aβ binding using a calculation model consisting of a GM1-containing mixed lipid membrane, water layer, ions, and Aβ40...
March 14, 2018: Journal of Physical Chemistry. B
Daria Tretiakova, Natalia Onishchenko, Ivan Boldyrev, Ilya Mikhalyov, Alexander Tuzikov, Nicolai Bovin, Evgeniy Evtushenko, Elena Vodovozova
Previously, we proposed a liposomal formulation of melphalan (Mlph)-a chemotherapeutic alkylating agent-incorporated in a fluid lipid bilayer in the form of dioleoylglyceride ester. In this work, we compared the stabilizing effect of different amphiphiles included in the Mlph-liposomes, such as phosphatidylinositol (PI), ganglioside GM1 , a conjugate of N-carboxymethyl-modified oligoglycine with dioleoylphosphatidylethanolamine (acidic lipopeptide), and polyethylene glycol (2000 Da) conjugated with dipalmitoylphosphatidylethanolamine (PEG-lipid), upon incubation in human serum...
March 1, 2018: Colloids and Surfaces. B, Biointerfaces
Xueheng Zhao, Marion G Brusadelli, Sharon L Sauter, Melinda Butsch Kovacic, Wujuan Zhang, Lindsey E Romick-Rosendale, Paul F Lambert, Kenneth D Setchell, Susanne I Wells
PURPOSE: Mutations in Fanconi anemia (FA) genes are common in sporadic squamous cell carcinoma of the head and neck (HNSCC) and we have previously demonstrated that FA pathway depletion in HNSCC cell lines stimulates invasion. The goal of our studies was to use a systems approach in order to define FA pathway-dependent lipid metabolism, and to extract lipid-based signatures and effectors of invasion in FA-deficient cells. EXPERIMENTAL DESIGN: We subjected FA-isogenic HNSCC keratinocyte cell lines to untargeted and targeted lipidomics analyses to discover novel biomarkers and candidate therapeutic targets in FA-deficient cells...
March 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Miriam Palacios, Ricardo Tampe, Miguel Del Campo, Ta-Ying Zhong, Mercedes N López, Flavio Salazar-Onfray, María Inés Becker
Conjugation to carrier proteins is a way to improve the immunogenicity of peptides. Such is the case for peptides mimicking carbohydrate tumor-associated antigens in cancer vaccine development. The most used protein for this purpose is the keyhole limpet hemocyanin (KLH) from Megathura crenulata. Its limited bioavailability has prompted interest in finding new candidates; nevertheless, it is not known whether other hemocyanins might be equally efficient as carrier of carbohydrate peptide mimotopes to promotes anti-tumor responses...
February 27, 2018: European Journal of Medicinal Chemistry
Yoko Maruyama, Satoko Ueno, Mitsuhiro Morita, Fumio Hayashi, Shohei Maekawa
Neurons have well-developed membrane microdomains called "rafts" that are recovered as a detergent-resistant membrane microdomain fraction (DRM). NAP-22 is one of the major protein components of neuronal DRM. In a previous study, we showed that DRM-derived NAP-22 binds ganglioside and the inhibitory effect of ganglioside to calcineurin (CaN), a neuron-enriched calmodulin-regulated phosphoprotein phosphatase. Considering the important roles of CaN in neurons, identification of other cellular regulators of CaN could be a good clue to understand the molecular background of neuronal function...
March 7, 2018: Neuroscience Letters
G Charles Ostermeier, Cristina Cardona, Melissa A Moody, Alana J Simpson, Romeo Mendoza, Eric Seaman, Alexander J Travis
Sperm must mature functionally in the process of capacitation to become able to fertilize. Capacitation depends on membrane lipid changes, and can be quantitatively assessed by redistribution of the ganglioside GM1 , the basis of the Cap-Score™ sperm function test. Here, differences in Cap-Score were compared among and within men at two time points. Ejaculates were liquefied, washed, and incubated for 3 hours under capacitating (Cap) conditions, then fixed and analyzed immediately (Day0); after being incubated 3 hours under Cap conditions then maintained 22-24 hours in fix (Day1-fix); or after 22-24 hours incubation under Cap conditions prior to fixation (Day1)...
March 9, 2018: Molecular Reproduction and Development
Sayantani Sarkar Bhattacharya, Chandan Mandal, Reinhard Schwartz Albiez, Suman Kumar Samanta, Chitra Mandal
Endoplasmic reticulum (ER) stress results from protein unfolding/misfolding during cellular maturation, which requires a coordinated action of several chaperones and enzymes and Ca2+ signalling. ER-stress possibly has a positive effect on survival of pancreatic cancer cell. Therefore, detailed insights into this complex signaling network are urgently needed. Here, we systematically analyzed the impact of ER stress-mediated unfolded protein response (UPR) and Ca2+ -signaling cross-talk for the survival of pancreatic adenocarcinoma (PDAC) cells...
March 2, 2018: Scientific Reports
Ida Annunziata, Renata Sano, Alessandra d'Azzo
Lysosomal storage diseases (LSDs) comprise a large group of disorders of catabolism, mostly due to deficiency of a single glycan-cleaving hydrolase. The consequent endo-lysosomal accumulation of undigested or partially digested substrates in cells of virtually all organs, including the nervous system, is diagnostic of these diseases and underlies pathogenesis. A subgroup of LSDs, the glycosphingolipidoses, are caused by deficiency of glycosidases that process/degrade sphingolipids and glycosphingolipids (GSLs)...
February 28, 2018: Cell Death & Disease
John Benktander, Angela Barone, Miralda Madar Johansson, Susann Teneberg
Adhesion of Helicobacter pylori to the gastric mucosa is a prerequisite for the pathogenesis of H. pylori related diseases. In this study, we investigated the ganglioside composition of human stomach as the target for attachment mediated by H. pylori SabA (sialic acid binding adhesin). Acid glycosphingolipids were isolated from human stomach and separated into subfractions, which were characterized by mass spectrometry and by binding of antibodies, bacteria, and Solanum tuberosum lectin. H. pylori SabA binding gangliosides were characterized as Neu5Acα3-neolactohexaosylceramide and Neu5Acα3-neolactooctaosylceramide, while the other acid human stomach glycosphingolipids characterized (sulfatide and the gangliosides GM3, GD3, GM1, Neu5Acα3-neolactotetraosylceramide, GD1a and GD1b) were not recognized by the bacteria...
February 23, 2018: Virulence
Aleksandra Somogyi, Anton Petcherski, Benedikt Beckert, Mylene Huebecker, David A Priestman, Antje Banning, Susan L Cotman, Frances M Platt, Mika O Ruonala, Ritva Tikkanen
Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3 gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. A genetically accurate mouse model ( Cln3 Δex7/8 mice) for this deletion has been generated. Using cerebellar precursor cell lines generated from wildtype and Cln3 Δex7/8 mice, we have here analyzed the consequences of the CLN3 deletion on levels of cellular gangliosides, particularly GM3, GM2, GM1a and GD1a...
February 22, 2018: International Journal of Molecular Sciences
Norihiko Sasaki, Yoko Itakura, Masashi Toyoda
Vascular insulin resistance induced by inflammatory cytokines leads to the initiation and development of vascular diseases. In humans, circulating TNFα levels are increased during aging, suggesting a correlation between vascular insulin resistance and plasma TNFα levels. Currently, the precise molecular mechanisms of vascular insulin resistance mediated by TNFα are not well characterized. We aimed at clarifying whether glycosphingolipids contribute to vascular insulin resistance after inflammatory stimulation...
January 19, 2018: Oncotarget
Inês Gomes Ferreira, Michela Pucci, Giulia Venturi, Nadia Malagolini, Mariella Chiricolo, Fabio Dall'Olio
Glycosylation is a very frequent and functionally important post-translational protein modification that undergoes profound changes in cancer. Growth and death factor receptors and plasma membrane glycoproteins, which upon activation by extracellular ligands trigger a signal transduction cascade, are targets of several molecular anti-cancer drugs. In this review, we provide a thorough picture of the mechanisms bywhich glycosylation affects the activity of growth and death factor receptors in normal and pathological conditions...
February 15, 2018: International Journal of Molecular Sciences
Emad Kordbacheh, Shahram Nazarian, Abbas Hajizadeh, Davood Sadeghi
Vaccine delivery vehicles are just as important in vaccine efficiency. Through the progress in nanotechnology, various nanoparticles have been evaluated as carriers for these substances. Among them, alginate nanoparticles are a good choice because of their biodegradability, biocompatibility, ease of production, etc. In this study, feasibility of alginate nanoparticles (NPs) such as recombinant LTB from Enterotoxigenic Escherichia coli (ETEC) carrier was investigated. To do this, the eltb gene was cloned and expressed in E...
February 20, 2018: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
John Forsayeth, Piotr Hadaczek
Here we advance the hypothesis that Parkinson's disease (PD) is fundamentally a failure of trophic support for specific classes of neurons, primarily catecholaminergic. Evidence from our laboratory provides a framework into which a broad array of findings from many quarters can be integrated into a general theory that offers testable hypotheses to new and established investigators. Mice deficient in the ability to synthesize series-a gangliosides, specifically GM1 ganglioside, develop parkinsonism. We found that this seems to be due to a failure in signaling efficiency by the important catecholaminergic growth factor, GDNF...
2018: Frontiers in Neuroscience
Alejandra Culebro, Miguel P Machado, João André Carriço, Mirko Rossi
Campylobacter jejuni and Campylobacter coli are the most common cause of bacterial gastroenteritis worldwide. Additionally, C. jejuni is the most common bacterial etiological agent in the autoimmune Guillain-Barré syndrome (GBS). Ganglioside mimicry by C. jejuni lipooligosaccharide (LOS) is the triggering factor of the disease. LOS-associated genes involved in the synthesis and transfer of sialic acid (glycosyltranferases belonging to family GT-42) are essential in C. jejuni to synthesize ganglioside-like LOS...
February 14, 2018: Scientific Reports
Weihong Zhu, Xinzhan Mao, Wanchun Wang, You Chen, Ding Li, Hui Li, Pengcheng Dou
Cisplatin is an effective chemotherapeutic agent for osteosarcoma (OS) and has been shown to induce endoplasmic reticulum (ER) stress-associated apoptosis in human cancer cells. Ganglioside GD2-specific antibodies can inhibit tumor cell viability without involvement of the immune system. A recent study has shown that antiGD2 monoclonal antibody (mAb) 14G2a effectively inhibits the viability and invasiveness of human OS cells. In this study, we explored the effect of anti-GD2 mAb and cisplatin alone and in combination on ER stress-associated apoptosis in osteosarcoma cells...
February 1, 2018: Die Pharmazie
Taiji Iwasawa, Pu Zhang, Yuki Ohkawa, Hiroyuki Momota, Toshihiko Wakabayashi, Yuhsuke Ohmi, Robiul H Bhuiyan, Keiko Furukawa, Koichi Furukawa
Sialic acid-containing glycosphingolipids, gangliosides, are considered as cancer associated antigens in neuro-ectoderm-derived tumors such as melanomas and neuroblastomas. In particular, gangliosides GD3 and GD2 are expressed in human gliomas. It has been reported that their expression levels increase along with increased malignant properties. However, the implication of GD3/GD2 in human glioma cells has never been clarified, at least to the best of our knowledge. In this study, we introduced the cDNA of GD3 synthase (GD3S)(ST8SIA1) into a glioma cell line, U-251MG, that expresses neither GD3 nor GD2, thereby establishing transfectant cells U-251MG-GD3S(+) expressing high levels of GD3 and GD2 on the cell surface...
February 7, 2018: International Journal of Oncology
Haruki Koike
Recent studies revealed an association between Zika virus infection and a variety of neurological disorders, including microcephaly, meningoencephalitis, myelitis, and Guillain-Barré syndrome (GBS). Following the first report of a patient diagnosed with GBS after Zika virus infection in December 2013, the number of GBS patients significantly increased in endemic countries, such as French-Polynesia and Latin American countries. Electrophysiological studies suggested that patients suffering from GBS associated with Zika virus infection manifest acute inflammatory demyelinating polyneuropathy (AIDP), rather than acute motor axonal neuropathy (AMAN)...
February 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
Jakob Cervin, Amberlyn M Wands, Anna Casselbrant, Han Wu, Soumya Krishnamurthy, Aleksander Cvjetkovic, Johanna Estelius, Benjamin Dedic, Anirudh Sethi, Kerri-Lee Wallom, Rebecca Riise, Malin Bäckström, Ville Wallenius, Frances M Platt, Michael Lebens, Susann Teneberg, Lars Fändriks, Jennifer J Kohler, Ulf Yrlid
Cholera toxin (CT) enters and intoxicates host cells after binding cell surface receptors via its B subunit (CTB). We have recently shown that in addition to the previously described binding partner ganglioside GM1, CTB binds to fucosylated proteins. Using flow cytometric analysis of primary human jejunal epithelial cells and granulocytes, we now show that CTB binding correlates with expression of the fucosylated Lewis X (LeX) glycan. This binding is competitively blocked by fucosylated oligosaccharides and fucose-binding lectins...
February 12, 2018: PLoS Pathogens
Zhahirul Islam, Israt Jahan, Rijwan U Ahammad, Mohammad Shahnaij, Shamsun Nahar, Quazi D Mohammad
Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system triggered by molecular mimicry between pathogen lipopolysaccharides and host nerve gangliosides. Polymorphisms in the Fas receptor (FAS) and Fas ligand (FASL) genes may potentially alter the elimination of autoreactive immune cells and affect disease susceptibility or disease severity in GBS. We detected single nucleotide polymorphisms (SNPs) in FAS (-1377G/A and -670A/G) and FASL (-843C/T) in a prospective cohort of 300 patients with GBS and 300 healthy controls from the Bangladeshi population...
2018: PloS One
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