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Anide Johansen, Rasim O Rosti, Damir Musaev, Evan Sticca, Ricardo Harripaul, Maha Zaki, Ahmet Okay Çağlayan, Matloob Azam, Tipu Sultan, Tawfiq Froukh, André Reis, Bernt Popp, Iltaf Ahmed, Peter John, Muhammad Ayub, Tawfeg Ben-Omran, John B Vincent, Joseph G Gleeson, Rami Abou Jamra
The risk of epilepsy among individuals with intellectual disability (ID) is approximately ten times that of the general population. From a cohort of >5,000 families affected by neurodevelopmental disorders, we identified six consanguineous families harboring homozygous inactivating variants in MBOAT7, encoding lysophosphatidylinositol acyltransferase (LPIAT1). Subjects presented with ID frequently accompanied by epilepsy and autistic features. LPIAT1 is a membrane-bound phospholipid-remodeling enzyme that transfers arachidonic acid (AA) to lysophosphatidylinositol to produce AA-containing phosphatidylinositol...
October 6, 2016: American Journal of Human Genetics
Bo Liu, Shuang Song, Inmaculada Ruz Maldonado, Attilio Pingitore, Guo C Huang, David Baker, Peter M Jones, Shanta J Persaud
AIMS: The novel cannabinoid receptor GPR55 is expressed by rodent islets and it has been implicated in β-cell function in response to a range of ligands. This study evaluated the effects of GPR55 ligands on intracellular calcium ([Ca(2+) ]i ) levels and insulin secretion from islets isolated from GPR55 knockout (GPR55(-/-) ) mice, age-matched wildtype (WT) mice, and human pancreas. MATERIALS AND METHODS: GPR55 expression was determined by western blotting and fluorescent immunohistochemistry...
August 26, 2016: Diabetes, Obesity & Metabolism
Yonghai Lu, Yeli Wang, Choon-Nam Ong, Tavintharan Subramaniam, Hyung Won Choi, Jian-Min Yuan, Woon-Puay Koh, An Pan
AIMS/HYPOTHESIS: Metabolomics has provided new insight into diabetes risk assessment. In this study we characterised the human serum metabolic profiles of participants in the Singapore Chinese Health Study cohort to identify metabolic signatures associated with an increased risk of type 2 diabetes. METHODS: In this nested case-control study, baseline serum metabolite profiles were measured using LC-MS and GC-MS during a 6-year follow-up of 197 individuals with type 2 diabetes but without a history of cardiovascular disease or cancer before diabetes diagnosis, and 197 healthy controls matched by age, sex and date of blood collection...
November 2016: Diabetologia
Bruno A Marichal-Cancino, Alfonso Fajardo-Valdéz, Alejandra E Ruiz-Contreras, Mónica Méndez-Díaz, Oscar Prospéro-García
The G protein-coupled receptor 55 (GPR55) is a mammalian orphan receptor whose functions in the central nervous system (CNS) have been scarcely elucidated. Several endogenous lipids (cannabinoids and non-cannabinoid) may activate GPR55; these facts have raised a discussion about its nature as a putative cannabinoid receptor. Lysophosphatidylinositol (LPI) is a non-endocannabinoid lipid with activity as a full and potent agonist of GPR55. Beyond this controversy, it is known the endocannabinoid system and GPR55 are highly related both in anatomical localization and function...
July 29, 2016: Current Neuropharmacology
Ieva Ailte, Anne Berit Dyve Lingelem, Simona Kavaliauskiene, Jonas Bergan, Audun Sverre Kvalvaag, Anne-Grethe Myrann, Tore Skotland, Kirsten Sandvig
Shiga toxin (Stx), an AB5 toxin, binds specifically to the neutral glycosphingolipid Gb3 at the cell surface before being transported into cells. We here demonstrate that addition of conical lysophospholipids (LPLs) with large head groups inhibit Stx binding to cells whereas LPLs with small head groups do not. Lysophosphatidylinositol (LPI 18:0), the most efficient LPL with the largest head group, was selected for in-depth investigations to study how the binding of Stx is regulated. We show that the inhibition of Stx binding by LPI is reversible and possibly regulated by cholesterol since addition of methyl-β-cyclodextrin (mβCD) reversed the ability of LPI to inhibit binding...
2016: Scientific Reports
Clara Andradas, Sandra Blasco-Benito, Sonia Castillo-Lluva, Patricia Dillenburg-Pilla, Rebeca Diez-Alarcia, Alba Juanes-García, Elena García-Taboada, Rodrigo Hernando-Llorente, Joaquim Soriano, Sigrid Hamann, Antonia Wenners, Ibrahim Alkatout, Wolfram Klapper, Christoph Rocken, Maret Bauer, Norbert Arnold, Miguel Quintanilla, Diego Megías, Miguel Vicente-Manzanares, Leyre Urigüen, J Silvio Gutkind, Manuel Guzmán, Eduardo Pérez-Gómez, Cristina Sánchez
The orphan G protein-coupled receptor GPR55 has been directly or indirectly related to basic alterations that drive malignant growth: uncontrolled cancer cell proliferation, sustained angiogenesis, and cancer cell adhesion and migration. However, little is known about the involvement of this receptor in metastasis. Here, we show that elevated GPR55 expression in human tumors is associated with the aggressive basal/triple-negative breast cancer population, higher probability to develop metastases, and therefore poor patient prognosis...
June 21, 2016: Oncotarget
Toshihiko Aiba, Masaki Sato, Daichi Umegaki, Takanori Iwasaki, Nobuaki Kambe, Koichi Fukase, Yukari Fujimoto
A regioselective phosphorylation method for myo-inositol was developed by utilizing readily preparable BINOL-derived phosphoramidites. The method also facilitated the complete separation of the diastereomeric products by simple chromatography. Based on this phosphorylation and Ni-catalyzed alkyl-alkyl cross-coupling reaction for long fatty acids, we achieved the first synthesis of a lysophosphatidylinositol, EhPIa having long fatty acid C30:1, as a partial structure of glycosylphosphatidylinositol (GPI) anchor from the cell membrane of a protozoa, Entamoeba histolytica...
July 12, 2016: Organic & Biomolecular Chemistry
Josep M Del Bas, Antoni Caimari, Maria Isabel Rodriguez-Naranjo, Caroline E Childs, Carolina Paras Chavez, Annette L West, Elizabeth A Miles, Lluis Arola, Philip C Calder
BACKGROUND: Plasma lysophospholipids have emerged as signaling molecules with important effects on inflammation, insulin resistance, and fatty liver disease, each of which is linked closely to obesity. Dietary n-3 (ω-3) polyunsaturated fatty acids (PUFAs) may be able to improve these conditions. OBJECTIVE: The objective of this study was to assess the response of plasma lysophospholipids to obesity, n-3 PUFA consumption, and a high-fat meal challenge to better understand the role of lysophospholipid metabolism in the progression of obesity-related disorders...
August 2016: American Journal of Clinical Nutrition
Sharon Anavi-Goffer, Ruth A Ross
AlphaScreen(®) SureFire(®) assay is a novel technology that combines luminescent oxygen channeling technology, nano-beads, and monocloncal antibodies to detect the level of a selected protein in a volume lower than 5 μl. This method is more sensitive compared with the traditional enzyme-linked immunosorbent assays (ELISA), and can detect an increasing number of new targets. Here, we described a method for AlphaScreen(®) SureFire(®) assay that targets ERK1/2 phosphorylation, a primary downstream signaling pathway that conveys activation of GPR55 by L-α-lysophosphatidylinositol (LPI) and certain cannabinoids...
2016: Methods in Molecular Biology
Julien Masquelier, Giulio G Muccioli
Increasing evidence suggests that lysophosphatidylinositols (LPIs), a subspecies of lysophospholipids, are important endogenous mediators. Although LPIs long remained among the less studied lysophospholipids, the identification of GPR55 as their molecular target sparked a renewed interest in the study of these bioactive lipids. Furthermore, increasing evidence points towards a role for LPIs in cancer development. However, a better understanding of the role and functions of LPIs in physiology and disease requires methods that allow for the quantification of LPI levels in cells and tissues...
July 15, 2016: Journal of Pharmaceutical and Biomedical Analysis
Sharon Anavi-Goffer, Andrew J Irving, Ruth A Ross
BACKGROUND: GPR55 is a lipid-sensing G protein-coupled receptor that is activated by the endogenous lipid l-α-lysophosphatidylinositol (LPI) and can be modulated by certain cannabinoid ligands. METHODS: In this study we investigated the GPR55 activity of four synthetic CB2 receptor agonists using the AlphaScreen® SureFire® assay. RESULTS: Here we show that the CB2 receptor-selective agonists HU-308, HU-433 and HU-910 do not promote GPR55-mediated ERK1/2 phosphorylation up to a concentration of 3 μM...
May 1, 2016: Journal of Basic and Clinical Physiology and Pharmacology
Paula Morales, Lauren S Whyte, Roberto Chicharro, María Gómez-Cañas, M Ruth Pazos, Pilar Goya, Andrew J Irving, Javier Fernández-Ruiz, Ruth A Ross, Nadine Jagerovic
The orphan G protein-coupled receptor GPR55 has been proposed as a novel receptor of the endocannabinoid system. However, the validity of this categorization is still under debate mainly because of the lack of potent and selective agonists and antagonists of GPR55. Binding assays are not yet available for GPR55 screening, and discrepancies in GPR55 mediated signaling pathways have been reported. In this context, we have designed and synthesized novel GPR55 ligands based on a chromenopyrazole scaffold. Appraisal of GPR55 activity was accomplished using a label-free cell-impedance-based assay in hGPR55-HEK293 cells...
March 10, 2016: Journal of Medicinal Chemistry
Syamsul A Arifin, Marco Falasca
Metabolism is a chemical process used by cells to transform food-derived nutrients, such as proteins, carbohydrates and fats, into chemical and thermal energy. Whenever an alteration of this process occurs, the chemical balance within the cells is impaired and this can affect their growth and response to the environment, leading to the development of a metabolic disease. Metabolic syndrome, a cluster of several metabolic risk factors such as abdominal obesity, insulin resistance, high cholesterol and high blood pressure, and atherogenic dyslipidaemia, is increasingly common in modern society...
2016: Metabolites
Makoto Kurano, Tomotaka Dohi, Takahiro Nojiri, Tamaki Kobayashi, Yuji Hirowatari, Asuka Inoue, Kuniyuki Kano, Hirotaka Matsumoto, Koji Igarashi, Masako Nishikawa, Katsumi Miyauchi, Hiroyuki Daida, Hitoshi Ikeda, Junken Aoki, Yutaka Yatomi
BACKGROUNDS: Glycero-lysophospholipids (glycero-LPLs), which are known to exert potent biological activities, have been demonstrated to be secreted from activated platelets in vitro; however, their association with platelet activation in vivo has not been yet elucidated. In this study, we investigated the correlations between the blood levels of each glycero-LPL and serotonin, a biomarker of platelet activation, in human subjects to elucidate the involvement of platelet activation in glycero-LPLs in vivo...
December 2015: BBA Clinical
Anne Julie Overgaard, Jacquelyn M Weir, David Peter De Souza, Dedreia Tull, Claus Haase, Peter J Meikle, Flemming Pociot
The early mechanisms regulating progression towards beta cell failure in type 1 diabetes (T1D) are poorly understood, but it is generally acknowledged that genetic and environmental components are involved. The metabolomic phenotype is sensitive to minor variations in both, and accordingly reflects changes that may lead to the development of T1D. We used two different extraction methods in combination with both liquid- and gas chromatographic techniques coupled to mass spectrometry to profile the metabolites in a transgenic non-diabetes prone C57BL/6 mouse expressing CD154 under the control of the rat insulin promoter (RIP) crossed into the immuno-deficient recombination-activating gene (RAG) knockout (-/-) C57BL/6 mouse, resembling the early stages of human T1D...
2016: Metabolomics: Official Journal of the Metabolomic Society
Y M Al Suleimani, C R Hiley
The lipid molecule, lysophosphatidylinositol (LPI), is hypothesised to form part of a novel lipid signalling system that involves the G protein-coupled receptor GPR55 and distinct intracellular signalling cascades in endothelial cells. This work aimed to study the possible mechanisms involved in LPI-evoked cytosolic Ca(2+) mobilization in human brain microvascular endothelial cells. Changes in intracellular Ca(2+) concentrations were measured using cell population Ca(2+) assay. LPI evoked biphasic elevation of intracellular calcium concentration, a rapid phase and a sustained phase...
2016: Physiological Research
J Kargl, L Andersen, C Hasenöhrl, D Feuersinger, A Stančić, A Fauland, C Magnes, A El-Heliebi, S Lax, S Uranitsch, J Haybaeck, A Heinemann, R Schicho
BACKGROUND AND PURPOSE: Tumour cell migration and adhesion constitute essential features of metastasis. G-protein coupled receptor 55 (GPR55), a lysophospholipid receptor, has been shown to play an important role in carcinogenesis. Here, we investigated the involvement of GPR55 in migration and metastasis of colon cancer cells. EXPERIMENTAL APPROACH: Adhesion and migration assays using the highly metastatic colon cancer cell line HCT116 and an in vivo assay of liver metastasis were performed...
January 2016: British Journal of Pharmacology
Si Zhu, Mengwei Ye, Jilin Xu, Chunyang Guo, Huakun Zheng, Jiabao Hu, Juanjuan Chen, Yajun Wang, Shanliang Xu, Xiaojun Yan
Jellyfish Rhopilema esculentum has been exploited commercially as a delicious food for a long time. Although the edible and medicinal values of R. esculentum have gained extensive attention, the effects of lipids on its nutritional value have rarely been reported. In the present of study, the lipid profile including lipid classes, fatty acyl compositions, and fatty acid (FA) positions in lipids from different parts (oral arms, umbrella, and mouth stalk) of R. esculentum was explored by ultraperformance liquid chromatography--electrospray ionization--quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS)...
September 23, 2015: Journal of Agricultural and Food Chemistry
Junhwan Kim, Joshua W Lampe, Tai Yin, Koichiro Shinozaki, Lance B Becker
Cardiac arrest (CA) induces whole-body ischemia, causing damage to multiple organs. Ischemic damage to the brain is mainly responsible for patient mortality. However, the molecular mechanism responsible for brain damage is not understood. Prior studies have provided evidence that degradation of membrane phospholipids plays key roles in ischemia/reperfusion injury. The aim of this study is to correlate organ damage to phospholipid alterations following 30 min asphyxia-induced CA or CA followed by cardiopulmonary bypass (CPB) resuscitation using a rat model...
October 2015: Molecular and Cellular Biochemistry
Han Li Sun, Tao Jiang
Nerve growth factor (NGF) is an important protein that is involved in a variety of physiological processes in cell survival, differentiation, proliferation and maintenance. The previously reported crystal structure of mouse NGF (mNGF) in complex with lysophosphatidylserine (LysoPS) showed that mNGF can bind LysoPS at its dimeric interface. To expand the understanding of the structural basis for specific lipid recognition by NGF, the crystal structure of mNGF complexed with lysophosphatidylinositol (13:0 LysoPI) was solved...
July 2015: Acta Crystallographica. Section F, Structural Biology Communications
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