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https://www.readbyqxmd.com/read/29023569/pancreatic-and-snake-venom-presynaptically-active-phospholipases-a2-inhibit-nicotinic-acetylcholine-receptors
#1
Catherine A Vulfius, Igor E Kasheverov, Elena V Kryukova, Ekaterina N Spirova, Irina V Shelukhina, Vladislav G Starkov, Tatyana V Andreeva, Grazyna Faure, Marios Zouridakis, Victor I Tsetlin, Yuri N Utkin
Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier demonstrated the capability of several snake venom PLA2s with different enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs) and acetylcholine binding protein...
2017: PloS One
https://www.readbyqxmd.com/read/28994599/a-metabolomics-and-lipidomics-study-of-mouse-models-of-type-1-diabetes-highlights-divergent-metabolism-in-purine-and-tryptophan-metabolism-prior-to-disease-on-set
#2
Steven A Murfitt, Paula Zaccone, Xinzhu Wang, Animesh Acharjee, Yvonne Sawyer, Albert Koulman, Lee D Roberts, Anne Cooke, Julian Griffin
With the increase in incidence of type 1 diabetes (T1DM), particularly in Westernised societies, there is an urgent need to understand the early molecular and metabolic alterations that accompany the autoimmune disease. This is not least because in murine models early intervention can prevent the development of overt disease. In this study we have applied a liquid chromatography (LC-) and gas chromatography (GC-) mass spectrometry (MS) metabolomics and lipidomics analysis of blood plasma and pancreas tissue extracts to follow the progression of disease in three models related to autoimmune diabetes: the non-obese diabetic (NOD) mouse, which is susceptible to the development of autoimmune diabetes, and the NOD-E (transgenic NOD mice that express the I-E heterodimer of the major histocompatibility complex II) and NOD- severe combined immunodeficiency (SCID) mouse strains, two models protected from the development of diabetes...
October 10, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28975480/mechanism-of-phospholipid-hydrolysis-for-oyster-crassostrea-plicatula-phospholipids-during-storage-using-shotgun-lipidomics
#3
Qinsheng Chen, Xincen Wang, Peixu Cong, Yanjun Liu, Yuming Wang, Jie Xu, Changhu Xue
A fast and efficient shotgun lipidomics strategy was applied to analyze phospholipids (PL) in the oyster Crassostrea plicatula, including 29 species of phosphatidylcholine (PtdCho), 23 species of phosphatidylethanolamine (PtdEtn), 11 species of phosphatidylserine (PtdSer), 6 species of phosphatidylinositol (PtdIns), and 17 species of lysophospholipids (Lyso-PL). During storage at 4 °C for 7 days, the PL content decreased by 68.08%, but a significant increase in the FFA content was observed (from 63.11 to 318...
October 3, 2017: Lipids
https://www.readbyqxmd.com/read/28955975/identification-of-lysophosphatidylthreonine-with-an-aromatic-fatty-acid-surrogate-as-a-potent-inducer-of-mast-cell-degranulation
#4
Takayuki Kishi, Hiroki Kawana, Misa Sayama, Kumiko Makide, Asuka Inoue, Yuko Otani, Tomohiko Ohwada, Junken Aoki
Upon various stimulations, mast cells (MCs) release a wide variety of chemical mediators stored in their cytoplasmic granules, which then initiates subsequent allergic reactions. Lysophosphatidylserine (LysoPS), a kind of lysophospholipid, potentiates the histamine release from MCs triggered by antigen stimulation. We previously showed through structure-activity studies of LysoPS analogs that LysoPS with a methyl group at the carbon of the serine residue, i.e., lysophosphatidylthreonine (LysoPT), is extremely potent in stimulating the MC degranulation...
December 2016: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28934113/sphingosine-1-phosphate-signaling-and-its-pharmacological-modulation-in-allogeneic-hematopoietic-stem-cell-transplantation
#5
REVIEW
Philip Smith, Catherine O'Sullivan, Peter Gergely
Allogeneic haemopoietic stem cell transplantation (HSCT) is increasingly used to treat haematological malignant diseases via the graft-versus-leukaemia (GvL) or graft-versus-tumour effects. Although improvements in infectious disease prophylaxis, immunosuppressive treatments, supportive care, and molecular based tissue typing have contributed to enhanced outcomes, acute graft-versus-host disease and other transplant related complications still contribute to high mortality and significantly limit the more widespread use of HSCT...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28888983/the-arabidopsis-thaliana-lysophospholipid-acyltransferase-at1g78690p-acylates-lysocardiolipins
#6
Reuben M Moncada, Katherine J Blackshear, Teresa A Garrett
The Arabidopsis thaliana lysophospholipid acyltransferase At1g78690 acylates a variety of lysophospholipids such as lyso phosphatidylglycerol, lyso phosphatidylethanolamine and lyso phosphatidylserine. Despite di-acylate phosphatidylglycerol being a substrate, overexpression of At1g78690 in Escherichia coli leads to the accumulation of acyl-PG. Here we show that cardiolipin also accumulates in cells overexpressing At1g78690. To help try and explain this observation, we show, using a liquid chromatography mass spectrometry (LC-MS) based assay, that At1g78690 utilizes both mono- and di-lyso cardiolipin as an acyl acceptor...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28887514/dormant-5-lipoxygenase-in-inflammatory-macrophages-is-triggered-by-exogenous-arachidonic-acid
#7
Carlos A Sorgi, Simona Zarini, Sarah A Martin, Raphael L Sanchez, Rodrigo F Scandiuzzi, Miguel A Gijón, Carlos Guijas, Nicolas Flamand, Robert C Murphy, Lucia H Faccioli
The differentiation of resident tissue macrophages from embryonic precursors and that of inflammatory macrophages from bone marrow cells leads to macrophage heterogeneity. Further plasticity is displayed through their ability to be polarized as subtypes M1 and M2 in a cell culture microenvironment. However, the detailed regulation of eicosanoid production and its involvement in macrophage biology remains unclear. Using a lipidomics approach, we demonstrated that eicosanoid production profiles between bone marrow-derived (BMDM) and peritoneal macrophages differed drastically...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874705/serum-lysophospholipid-levels-are-altered-in-dyslipidemic-hamsters
#8
Susana Suárez-García, Antoni Caimari, Josep Maria Del Bas, Manuel Suárez, Lluís Arola
Dyslipidemias are common disorders that predispose individuals to severe diseases. It is known that healthy living habits can prevent dyslipidemias if they are diagnosed properly. Therefore, biomarkers that assist in diagnosis are essential. The aim of this study was to identify biomarkers of dyslipidemia progression, which in turn disclose its etiology. These findings will pave the way for examinations of the regulatory mechanisms involved in dyslipidemias. Hamsters were fed either a normal-fat diet (NFD) or a high-fat diet...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819110/development-and-assessment-of-a-lysophospholipid-based-deep-learning-model-to-discriminate-geographical-origins-of-white-rice
#9
Nguyen Phuoc Long, Dong Kyu Lim, Changyeun Mo, Giyoung Kim, Sung Won Kwon
Geographical origin determination of white rice has become the major issue of food industry. However, there is still lack of a high-throughput method for rapidly and reproducibly differentiating the geographical origins of commercial white rice. In this study, we developed a method that employed lipidomics and deep learning to discriminate white rice from Korea to China. A total of 126 white rice of 30 cultivars from different regions were utilized for the method development and validation. By using direct infusion-mass spectrometry-based targeted lipidomics, 17 lysoglycerophospholipids were simultaneously characterized within minutes per sample...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808297/secretory-phospholipase-a2-modified-hdl-rapidly-and-potently-suppresses-platelet-activation
#10
Sanja Curcic, Michael Holzer, Lisa Pasterk, Eva Knuplez, Thomas O Eichmann, Saša Frank, Robert Zimmermann, Rudolf Schicho, Akos Heinemann, Gunther Marsche
Levels of secretory phospholipases A2 (sPLA2) highly increase under acute and chronic inflammatory conditions. sPLA2 is mainly associated with high-density lipoproteins (HDL) and generates bioactive lysophospholipids implicated in acute and chronic inflammatory processes. Unexpectedly, pharmacological inhibition of sPLA2 in patients with acute coronary syndrome was associated with an increased risk of myocardial infarction and stroke. Given that platelets are key players in thrombosis and inflammation, we hypothesized that sPLA2-induced hydrolysis of HDL-associated phospholipids (sPLA2-HDL) generates modified HDL particles that affect platelet function...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28803982/specific-inhibition-of-xenorhabdus-hominickii-an-entomopathogenic-bacterium-against-different-types-of-host-insect-phospholipase-a2
#11
Md Sadekuzzaman, Yonggyun Kim
Phospholipase A2 (PLA2) hydrolyzes ester bond of phospholipids at the sn-2 position to release free fatty acid and lysophospholipids. Some PLA2s preferentially release arachidonic acid which is subsequently oxygenated into eicosanoids to mediate immune responses in insects. Xenorhabdus hominickii is an entomopathogenic bacterium that can suppress insect immunity by inhibiting PLA2 activity. However, little is known about target PLA2 types inhibited by X. hominickii. Therefore, the objective of this study was to determine PLA2 types in the host insect, Spodoptera exigua using specific inhibitors...
August 10, 2017: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/28801536/structure-annotation-and-quantification-of-wheat-seed-oxidized-lipids-by-high-resolution-lc-ms-ms
#12
David Riewe, Janine Wiebach, Thomas Altmann
Lipid oxidation is a process ubiquitous in life, but the direct and comprehensive analysis of oxidized lipids has been limited by available analytical methods. We applied high-resolution liquid chromatography-mass spectrometry (LC-MS) and tandem mass spectrometry (MS/MS) to quantify oxidized lipids (glycerides, fatty acids, phospholipids, lysophospholipids, and galactolipids) and implemented a platform-independent high-throughput-amenable analysis pipeline for the high-confidence annotation and acyl composition analysis of oxidized lipids...
October 2017: Plant Physiology
https://www.readbyqxmd.com/read/28798136/adipose-tissue-metabolic-and-inflammatory-responses-to-stroke-are-altered-in-obese-mice
#13
Michael J Haley, Graham Mullard, Katherine A Hollywood, Garth J Cooper, Warwick B Dunn, Catherine B Lawrence
Obesity is an independent risk factor for stroke, though several clinical studies have reported that obesity improves stroke outcome. Obesity is hypothesised to aid recovery by protecting against post-stroke catabolism. We therefore assessed whether obese mice had an altered metabolic and inflammatory response to stroke. Obese ob/ob mice underwent 20 min middle cerebral artery occlusion and 24 h reperfusion. Lipid metabolism and expression of inflammatory cytokines were assessed in the plasma, liver and adipose tissue...
August 10, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28790013/chronic-vitamin-e-deficiency-impairs-cognitive-function-in-adult-zebrafish-via-dysregulation-of-brain-lipids-and-energy-metabolism
#14
Melissa McDougall, Jaewoo Choi, Kathy Magnusson, Lisa Truong, Robert Tanguay, Maret G Traber
Zebrafish (Danio rerio) are a recognized model for studying the pathogenesis of cognitive deficits and the mechanisms underlying behavioral impairments, including the consequences of increased oxidative stress within the brain. The lipophilic antioxidant vitamin E (α-tocopherol; VitE) has an established role in neurological health and cognitive function, but the biological rationale for this action remains unknown. In the present study, we investigated behavioral perturbations due to chronic VitE deficiency in adult zebrafish fed from 45 days to 18-months of age diets that were either VitE-deficient (E-) or VitE-sufficient (E+)...
November 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28771545/augmented-sphingosine-1-phosphate-receptor-1-signaling-in-cardiac-fibroblasts-induces-cardiac-hypertrophy-and-fibrosis-through-angiotensin-ii-and-interleukin-6
#15
Sei-Ichiro Ohkura, Soichiro Usui, Shin-Ichiro Takashima, Noriko Takuwa, Kazuaki Yoshioka, Yasuo Okamoto, Yutaka Inagaki, Naotoshi Sugimoto, Teppei Kitano, Masayuki Takamura, Takashi Wada, Shuichi Kaneko, Yoh Takuwa
Cardiac fibroblasts, together with cardiomyocytes, occupy the majority of cells in the myocardium and are involved in myocardial remodeling. The lysophospholipid mediator sphigosine-1-phosphate (S1P) regulates functions of cardiovascular cells through multiple receptors including S1PR1-S1PR3. S1PR1 but not other S1P receptors was upregulated in angiotensin II-induced hypertrophic hearts. Therefore, we investigated a role of S1PR1 in fibroblasts for cardiac remodeling by employing transgenic mice that overexpressed S1PR1 under the control of α-smooth muscle actin promoter...
2017: PloS One
https://www.readbyqxmd.com/read/28765606/2-oxoesters-a-novel-class-of-potent-and-selective-inhibitors-of-cytosolic-group-iva-phospholipase-a2
#16
Maroula G Kokotou, Gerasimia Galiatsatou, Victoria Magrioti, Giorgos Koutoulogenis, Efrosini Barbayianni, Dimitris Limnios, Varnavas D Mouchlis, Banita Satpathy, Aaron Navratil, Edward A Dennis, George Kokotos
Cytosolic phospholipase A2 (GIVA cPLA2) is the only PLA2 that exhibits a marked preference for hydrolysis of arachidonic acid containing phospholipid substrates releasing free arachidonic acid and lysophospholipids and giving rise to the generation of diverse lipid mediators involved in inflammatory conditions. Thus, the development of potent and selective GIVA cPLA2 inhibitors is of great importance. We have developed a novel class of such inhibitors based on the 2-oxoester functionality. This functionality in combination with a long aliphatic chain or a chain carrying an appropriate aromatic system, such as the biphenyl system, and a free carboxyl group leads to highly potent and selective GIVA cPLA2 inhibitors (X I(50) values 0...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28765047/lysophosphatidic-acid-directly-induces-macrophage-derived-foam-cell-formation-by-blocking-the-expression-of-srbi
#17
Linmu Chen, Jun Zhang, Xiao Deng, Yan Liu, Xi Yang, Qiong Wu, Chao Yu
The leading cause of morbidity and mortality is the result of cardiovascular disease, mainly atherosclerosis. The formation of macrophage foam cells by ingesting ox-LDL and focal retention in the subendothelial space are the hallmarks of the early atherosclerotic lesion. Lysophosphatidic acid (LPA), which is a low-molecular weight lysophospholipid enriched in oxidized LDL, exerts a range of effects on the cardiovascular system. Previous reports show that LPA increases the uptake of ox-LDL to promote the formation of foam cells...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28762322/optimized-mass-spectrometry-based-metabolite-extraction-and-analysis-for-the-geographical-discrimination-of-white-rice-oryza-sativa-l-a-method-comparison-study
#18
Dong Kyu Lim, Nguyen Phuoc Long, Changyeun Mo, Ziyuan Dong, Jongguk Lim, Sung Won Kwon
In this study, we examined the effects of different extraction methods for the GC-MS- and LC-MS-based metabolite profiling of white rice (Oryza sativa L.). In addition, the metabolite divergence of white rice cultivated in either Korea or China was also evaluated. The discrimination analysis of each extraction method for white rice from Korea and China and the corresponding discriminatory markers were estimated by unpaired t-test, principal component analysis, k-means cluster analysis, partial least-squares discriminant analysis (PLS-DA), and random forest (RF)...
July 31, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28760979/phospholipase-a-activity-of-adenylate-cyclase-toxin-mediates-translocation-of-its-adenylate-cyclase-domain
#19
David González-Bullón, Kepa B Uribe, César Martín, Helena Ostolaza
Adenylate cyclase toxin (ACT or CyaA) plays a crucial role in respiratory tract colonization and virulence of the whooping cough causative bacterium Bordetella pertussis Secreted as soluble protein, it targets myeloid cells expressing the CD11b/CD18 integrin and on delivery of its N-terminal adenylate cyclase catalytic domain (AC domain) into the cytosol, generates uncontrolled toxic levels of cAMP that ablates bactericidal capacities of phagocytes. Our study deciphers the fundamentals of the heretofore poorly understood molecular mechanism by which the ACT enzyme domain directly crosses the host cell membrane...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28750813/methods-for-the-development-of-in-silico-gpcr-models
#20
Paula Morales, Dow P Hurst, Patricia H Reggio
The Reggio group has constructed computer models of the inactive and G-protein-activated states of the cannabinoid CB1 and CB2 receptors, as well as, several orphan receptors that recognize a subset of cannabinoid compounds, including GPR55 and GPR18. These models have been used to design ligands, mutations, and covalent labeling studies. The resultant second-generation models have been used to design ligands with improved affinity, efficacy, and subtype selectivity. Herein, we provide a guide for the development of GPCR models using the most recent orphan receptor studied in our lab, GPR3...
2017: Methods in Enzymology
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