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Alejandro Melero, Nicolas Chiaruttini, Takefumi Karashima, Isabelle Riezman, Kouichi Funato, Charles Barlowe, Howard Riezman, Aurélien Roux
Coat protein complex II (COPII) proteins form vesicles from the endoplasmic reticulum to export cargo molecules to the Golgi apparatus. Among the many proteins involved in this process, Sec12 is a key regulator, functioning as the guanosine diphosphate (GDP) exchange factor for Sar1p, the small guanosine triphosphatase (GTPase) that initiates COPII assembly. Here we show that overexpression of phospholipase B3 in the thermosensitive sec12-4 mutant partially restores growth and protein transport at non-permissive temperatures...
May 31, 2018: Current Biology: CB
Suguru Yamamoto
Uremic toxins are linked to chronic kidney disease (CKD)-related systemic diseases. β2 -Microglobulin (β2 -m), a water-soluble, middle-sized molecule, is associated with mortality and dialysis-related amyloidosis (DRA). DRA occurs in long-term dialysis patients, with β2 -m amyloid deposited mainly in osteoarticular tissues. We investigated a model of β2 -m amyloid fibril extension at neutral pH in the presence of trifluoroethanol or sodium dodecyl sulfate. Using this model, some biological molecules, including glycosaminoglycans and lysophospholipids, were found to be chaperones for β2 -m amyloid fibril extension...
June 5, 2018: Clinical and Experimental Nephrology
Emanuel Bott, Alan B Carneiro, Guadalupe Gimenez, María G López, Estela M Lammel, Georgia C Atella, Patricia T Bozza, María L Belaunzarán
Lipids from microorganisms are ligands of Toll like receptors (TLRs) and modulate the innate immune response. Herein, we analyze in vitro the effect of total lipid extracts from Trypanosoma cruzi amastigotes of RA and K98 strains (with polar biological behavior) on the induction of the inflammatory response and the involvement of TLRs in this process. We demonstrated that total lipid extracts from both strains induced lipid body formation, cyclooxygenase-2 expression and TNF-α and nitric oxide release in macrophages, as well as NF-κB activation and IL-8 release in HEK cells specifically through a TLR2/6 dependent pathway...
2018: Frontiers in Cellular and Infection Microbiology
Hai-Yan Wang, Yi Wang, Yuan Zhang, Jing Wang, Shu-Yu Xiong, Qian Sun
AIM: To explore the roles of phospholipids and sphingolipids in the inflammatory process of uveitis. METHODS: Aqueous humor (AH) and the retina were obtained from endotoxin-induced uveitis (EIU) rats during the acute inflammation stage (24h after endotoxin injection). Lipids were extracted using a modified Bligh and Dyer method and subjected to mass spectrometric identification using class-specific lipid standards and ratiometric quantification. Relative intensity analysis was performed to evaluate the amount change of common lipids between the EIU and control groups...
2018: International Journal of Ophthalmology
Nor Aliza Abdul Rahim, Marlini Othman, Muna Sabri, David W Stanley
Phospholipase A2 (PLA2 ) is a secretory digestive enzyme that hydrolyzes ester bond at sn-2 position of dietary phospholipids, creating free fatty acid and lysophospholipid. The free fatty acids (arachidonic acid) are absorbed into midgut cells. Aedes albopictus and Culex quinquefasciatus digestive PLA2 was characterized using a microplate PLA2 assay. The enzyme showed substantial activities at 6 and 8  μ g/ μ l of protein concentration with optimal activity at 20 and 25  μ g/ μ l of substrate concentration in Aedes albopictus and Culex quinquefasciatus , respectively...
2018: Enzyme Research
J Hofmanová, J Slávik, Z Tylichová, P Ovesná, J Bouchal, Z Kolář, J Ehrmann, M Levková, M Machala, J Vondráček, A Kozubík
BACKGROUNDS: Colon cancer development is often characterized by abnormalities in lipid synthesis and metabolism, which may influence energetic balance, structure and function of biological membranes, or production of specific mediators and cell signalling. The changes in lipid profile and metabolism (lipidome) may significantly affect cell behaviour and response to therapy. Permanent epithelial cell lines at various stages of cancer development are used for better understanding of this topic on cellular and molecular levels...
2018: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Marc-Olivier Trépanier, Kathryn E Hopperton, Vanessa Giuliano, Mojgan Masoodi, Richard P Bazinet
Resolution of inflammation in the periphery was once thought to be a passive process, but new research now suggests it is an active process mediated by specialized pro-resolving lipid mediators (SPM) derived from omega-3 polyunsaturated fatty acids (n-3 PUFA). However, this has yet to be illustrated in neuroinflammation. The purpose of this study was to measure resolution of neuroinflammation and to test whether increasing brain docosahexaenoic acid (DHA) affects the resolution of neuroinflammation. C57Bl/6 mice, fat-1 mice and their wildtype littermates, fed either fish oil or safflower oil, received lipopolysaccharide (LPS) in the left lateral ventricle...
May 21, 2018: Neurochemistry International
Hang Wang, Hao Huang, Shi-Fang Ding
Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that involves in numerous pathophysiological processes. Endothelial progenitor cells (EPCs) play a crucial role in endothelial repair and tumor angiogenesis. The aim of study was to determine the effects of S1P on proliferation and anti-apoptosis of EPCs and their signaling pathways. In this study, we showed that S1P, SEW2871 (a selective S1P receptor 1 (S1PR1) agonist ), or CYM5541 (a selective S1P receptor 3 (S1PR3) allosteric agonist promotes the proliferation and attenuates apoptosis of bone marrow (BM)-derived EPCs...
May 23, 2018: Cell Biology International
Juanjuan Zhao, Yasuo Okamoto, Yuya Asano, Kazuhiro Ishimaru, Sho Aki, Kazuaki Yoshioka, Noriko Takuwa, Takashi Wada, Yutaka Inagaki, Chiaki Takahashi, Takumi Nishiuchi, Yoh Takuwa
Idiopathic pulmonary fibrosis is a devastating disease with poor prognosis. The pathogenic role of the lysophospholipid mediator sphingosine-1-phosphate and its receptor S1PR2 in lung fibrosis is unknown. We show here that genetic deletion of S1pr2 strikingly attenuated lung fibrosis induced by repeated injections of bleomycin in mice. We observed by using S1pr2LacZ/+ mice that S1PR2 was expressed in alveolar macrophages, vascular endothelial cells and alveolar epithelial cells in the lung and that S1PR2-expressing cells accumulated in the fibrotic legions...
2018: PloS One
Raphael Leblanc, Audrey Houssin, Olivier Peyruchaud
Platelets play a crucial role in the survival of metastatic cells in the blood circulation. Interaction of tumor cells with platelets leads to the production of plethoric factors among which our review will focus on lysophosphatidic acid (LPA) because platelets are the highest producers of this bioactive lysophospholipid in the organism. LPA promotes platelet aggregation and blocking platelet function leads to inhibition of breast cancer cell metastasis through decreased LPA signaling. Autotaxin (ATX), a lysophospholipase D responsible for basal concentration of LPA in blood, was detected in platelet α-granules...
May 19, 2018: British Journal of Pharmacology
Xinyuan Li, Luqiao Wang, Pu Fang, Yu Sun, Xiaohua Jiang, Hong Wang, Xiao-Feng Yang
Innate immune cells express danger-associated molecular pattern (DAMP) receptors, T-cell co-stimulation/co-inhibition receptors, and the major histocompatibility complex II (MHC-II). We have recently proposed that endothelial cells can serve as innate immune cells, but the molecular mechanisms involved still await discovery. Here, we investigated whether human aortic endothelial cells (HAECs) could be transdifferentiated into innate immune cells by exposing them to hyperlipidemia-upregulated DAMP molecules, i...
May 16, 2018: Journal of Biological Chemistry
Krizia Sagini, Eva Costanzi, Carla Emiliani, Sandra Buratta, Lorena Urbanelli
Over the last 20 years, extracellular vesicles (EVs) have been established as an additional way to transmit signals outside the cell. They are membrane-surrounded structures of nanometric size that can either originate from the membrane invagination of multivesicular bodies of the late endosomal compartment (exosomes) or bud from the plasma membrane (microvesicles). They contain proteins, lipids, and nucleic acids—namely miRNA, but also mRNA and lncRNA—which are derived from the parental cell, and have been retrieved in every fluid of the body...
April 18, 2018: International Journal of Molecular Sciences
Ibrahim Kaya, Henrik Zetterberg, Kaj Blennow, Jörg Hanrieder
Senile plaques formed by aggregated amyloid β peptides are one of the major pathological hallmarks of Alzheimer's disease (AD) which have been suggested to be the primary influence triggering the AD pathogenesis and the rest of the disease process. However, neurotoxic Aβ aggregation and progression are associated with a wide range of enigmatic biochemical, biophysical and genetic processes. MALDI imaging mass spectrometry (IMS) is a label-free method to elucidate the spatial distribution patterns of intact molecules in biological tissue sections...
May 4, 2018: ACS Chemical Neuroscience
Bradley Stockard, Timothy Garrett, Joy Guingab-Cagmat, Soheil Meshinchi, Jatinder Lamba
Acute myeloid leukemia (AML) is a heterogeneous disease with dismal response warranting the need for enhancing our understanding of AML biology. One prognostic feature associated with inferior response is the presence of activating mutations in FMS-like tyrosine kinase 3 (FLT3) especially occurrence of internal tandem duplication (FLT3-ITD). Although poorly understood, differential metabolic and signaling pathways associated with FLT3-ITD might contribute towards the observed poor prognosis. We performed a non-targeted global metabolic profiling of matched cell and plasma samples obtained at diagnosis to establish metabolic differences within FLT3-ITD and FLT3-WT pediatric AML...
April 3, 2018: Scientific Reports
Yoshikazu Konno, Akio Yoshimura, Noboru Naito, Kenji Aramaki
The formation of liquid ordered (Lo ) phase-like structures in stearyltrimethylammonium chloride/cholesterol/1,3-butanediol/water and hepta(oxyethylen) octadecyl ether/cholesterol/1,3-butanediol/water systems was investigated. Differential scanning calorimetry and X-ray scattering measurements confirmed that Lo phase-like structures were formed in both surfactant/cholesterol systems, similar to the lysophospholipid/cholesterol system. It was revealed that the concentration of cholesterol at which only Lo phase-like structures are formed increases in the order stearyltrimethylammonium chloride < lysophospholipid < hepta(oxyethylen) octadecyl ether...
2018: Journal of Oleo Science
Zeying He, Yuehua Wang, Yanwei Zhang, Haiyan Cheng, Xiaowei Liu
Stereoselective bioaccumulation, elimination, metabolomic and lipidomic responses of earthworm Eisenia fetida exposed to chiral polychlorinated biphenyl (PCB) 91 in an earthworm-soil system were investigated. Preferential bioaccumulation of (-)-PCB 91 and elimination of (+)-PCB 91 were observed following 50 and 500 μg/kgdwt exposures. Enantiomer fraction (EF) values decreased over time during the uptake and elimination periods. Metabolomics and lipidomics techniques based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) revealed significant changes in 108 metabolites after earthworms exposure to (+)-, (-)-, and (±)-PCB 91, compared to control groups...
July 2018: Environmental Pollution
Tomohiro Kimura, Atsuko K Kimura, Mindong Ren, Bob Berno, Yang Xu, Michael Schlame, Richard M Epand
Tafazzin is the mitochondrial enzyme that catalyzes transacylation between a phospholipid and a lysophospholipid in remodeling. Mutations in tafazzin cause Barth syndrome, a potentially life-threatening disease with the major symptom being cardiomyopathy. In the tafazzin-deficient heart, cardiolipin (CL) acyl chains become abnormally heterogeneous unlike those in the normal heart with a single dominant linoleoyl species, tetralinoleoyl CL. In addition, the amount of CL decreases and monolysocardiolipin (MLCL) accumulates...
April 10, 2018: Biochemistry
Amr S Ali, Ravali Raju, Somak Ray, Rashmi Kshirsagar, Alan Gilbert, Li Zang, Barry L Karger
As the demand for biological therapeutic proteins rises, there is an increasing need for robust and highly efficient bioprocesses, specifically, maximizing protein production by controlling the cellular nutritional and metabolic needs. A comprehensive lipidomics analysis has been performed, for the first time, over the time course of CHO cells producing an IgG1 monoclonal antibody (mAb) with fed batch 5 L bioreactors. The dynamic nature and importance of the CHO lipidome, especially on cellular growth and specific productivity, is demonstrated...
March 9, 2018: Biotechnology Journal
Caroline Serino-Silva, Karen Morais-Zani, Marcos Hikari Toyama, Daniela de Oliveira Toyama, Henrique Hessel Gaeta, Caroline Fabri Bittencourt Rodrigues, Wéslei da Silva Aguiar, Alexandre Keiji Tashima, Kathleen Fernandes Grego, Anita Mitico Tanaka-Azevedo
Phospholipases A2 (PLA2) are enzymes acting on the cell membrane phospholipids resulting in fatty acids and lysophospholipids and deconstructing the cell membrane. This protein is commonly found in snake venoms, causing tissue inflammation in the affected area. Evidence indicates that snakes have natural resistance to their own venom due to protective properties in plasma, that inhibit the action of proteins present in their venom. Given that, this study aimed to purify and characterize a γPLI from Bothrops jararaca serum, named γBjPLI...
2018: PloS One
Makoto Kurano, Tomomitsu Miyagaki, Takuya Miyagawa, Koji Igarashi, Satoshi Shimamoto, Hitoshi Ikeda, Junken Aoki, Shinichi Sato, Yutaka Yatomi
Autotaxin (ATX), a producing enzyme for lysophosphatidic acids, was first identified from the medium of a melanoma cell line and has been considered to be one of the candidate targets to treat melanoma; however, the association between serum ATX and melanoma in human subjects has not been elucidated. Along with ATX, phosphatidylserine-specific phospholipase A1 (PS-PLA1 ) is a producing enzyme for lysophosphatidylserine, a similar glycero-lysophospholipid mediator to lysophosphatidic acids. In the present study, we aimed to investigate the association between serum ATX or PS-PLA1 levels and melanoma...
May 2018: Journal of Dermatology
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