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1. Comprehensive bile acid pool analysis during ex-vivo liver perfusion in a porcine model of ischemia-reperfusion injury

Author

Guillaume Rossignol, Xavier Muller, Thomas Alexandre Brunet, Valeska Bidault, Valerie Hervieu, Yohann Clement, Sophie Ayciriex, Jean-Yves Mabrut, Arnaud Salvador, and Kayvan Mohkam

Subjects
Medicine, Science
Abstract

Abstract Bile acids (BA) are key for liver regeneration and injury. This study aims at analyzing the changes in the BA pool induced by ischemia-reperfusion (IRI) and investigates the impact of hypothermic oxygenated perfusion (HOPE) on the BA pool compared to static cold storage (SCS). In a porcine model of IRI, liver grafts underwent 30 min of asystolic warm ischemia followed by 6 h of SCS (n = 6) ± 2 h of HOPE (n = 6) and 2 h of ex-situ warm reperfusion. The BA pool in bile samples was analyzed with liquid chromatography coupled with tandem mass spectrometry. We identified 16 BA and observed significant changes in response to ischemia-reperfusion, which were associated with both protective and injury mechanisms. Second, HOPE-treated liver grafts exhibited a more protective BA phenotype, characterized by a more hydrophilic BA pool compared to SCS. Key BA, such as GlycoCholic Acid, were identified and were associated with a decreased transaminase release and improved lactate clearance during reperfusion. Partial Least Square-Discriminant Analysis revealed a distinct injury profile for the HOPE group. In conclusion, the BA pool changes with liver graft IRI, and preservation with HOPE results in a protective BA phenotype compared to SCS.

Published
2024
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4. Early detection of ureteropelvic junction obstruction in neonates with prenatal diagnosis of renal pelvis dilatation using 1H NMR urinary metabolomics

Author

Aurélien Scalabre, Yohann Clément, Florence Guillière, Sophie Ayciriex, Ségolène Gaillard, Delphine Demède, Aurore Bouty, Pierre Lanteri, and Pierre-Yves Mure

Subjects
Medicine, Science
Abstract

Abstract Renal pelvis dilatation (RPD) is diagnosed in utero on prenatal ultrasonography (US) and can resolve spontaneously. However, isolated RPD can also reflect ureteropelvic junction obstruction (UPJO), which requires surgical treatment to prevent progressive renal deterioration. The diagnosis of UPJO can only be confirmed after birth with repeat US and renal isotope studies. 1H Nuclear Magnetic Resonance spectroscopy (NMR) was performed on urine of newborns with prenatally diagnosed unilateral RPD and healthy controls to identify specific urinary biomarkers for UPJO. The original combination of EigenMS normalization and sparse partial-least-squares discriminant analysis improved selectivity and sensitivity. In total, 140 urine samples from newborns were processed and 100 metabolites were identified. Correlation network identified discriminant metabolites in lower concentrations in UPJO patients. Two main metabolic pathways appeared to be impaired in patients with UPJO i.e. amino acid and betaine metabolism. In this prospective study, metabolic profiling of urine samples by NMR clearly distinguishes patients who required surgery for UPJO from patients with transient dilatations and controls. This study will pave the way for the use of metabolomics for the diagnosis of prenatal hydronephrosis in clinical routine.

Published
2022
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5. Biallelic variants in TAMM41 are associated with low muscle cardiolipin levels, leading to neonatal mitochondrial disease

Author

Kyle Thompson, Lucas Bianchi, Francesca Rastelli, Florence Piron-Prunier, Sophie Ayciriex, Claude Besmond, Laurence Hubert, Magalie Barth, Inês A. Barbosa, Charu Deshpande, Manali Chitre, Sarju G. Mehta, Eric J.M. Wever, Pascale Marcorelles, Sandra Donkervoort, Dimah Saade, Carsten G. Bönnemann, Katherine R. Chao, Chunyu Cai, Susan T. Iannaccone, Andrew F. Dean, Robert McFarland, Frédéric M. Vaz, Agnès Delahodde, Robert W. Taylor, and Agnès Rötig

Subjects
cardiolipin, mitochondria, mitochondrial disease, WES/WGS, OXPHOS defect, mitochondrial phospholipid, Genetics, QH426-470
Abstract

Summary: Mitochondrial disorders are clinically and genetically heterogeneous, with variants in mitochondrial or nuclear genes leading to varied clinical phenotypes. TAMM41 encodes a mitochondrial protein with cytidine diphosphate-diacylglycerol synthase activity: an essential early step in the biosynthesis of phosphatidylglycerol and cardiolipin. Cardiolipin is a mitochondria-specific phospholipid that is important for many mitochondrial processes. We report three unrelated individuals with mitochondrial disease that share clinical features, including lethargy at birth, hypotonia, developmental delay, myopathy, and ptosis. Whole exome and genome sequencing identified compound heterozygous variants in TAMM41 in each proband. Western blot analysis in fibroblasts showed a mild oxidative phosphorylation (OXPHOS) defect in only one of the three affected individuals. In skeletal muscle samples, however, there was severe loss of subunits of complexes I–IV and a decrease in fully assembled OXPHOS complexes I–V in two subjects as well as decreased TAMM41 protein levels. Similar to the tissue-specific observations on OXPHOS, cardiolipin levels were unchanged in subject fibroblasts but significantly decreased in the skeletal muscle of affected individuals. To assess the functional impact of the TAMM41 missense variants, the equivalent mutations were modeled in yeast. All three mutants failed to rescue the growth defect of the Δtam41 strains on non-fermentable (respiratory) medium compared with wild-type TAM41, confirming the pathogenicity of the variants. We establish that TAMM41 is an additional gene involved in mitochondrial phospholipid biosynthesis and modification and that its deficiency results in a mitochondrial disorder, though unlike families with pathogenic AGK (Sengers syndrome) and TAFAZZIN (Barth syndrome) variants, there was no evidence of cardiomyopathy.

Published
2022
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6. Vitamin A Deficiency Alters the Phototransduction Machinery and Distinct Non-Vision-Specific Pathways in the Drosophila Eye Proteome

Author

Mukesh Kumar, Canan Has, Khanh Lam-Kamath, Sophie Ayciriex, Deepshe Dewett, Mhamed Bashir, Clara Poupault, Kai Schuhmann, Oskar Knittelfelder, Bharath Kumar Raghuraman, Robert Ahrends, Jens Rister, and Andrej Shevchenko

Subjects
Drosophila, retina, vitamin A, retinal, proteome, lipidome, Microbiology, QR1-502
Abstract

The requirement of vitamin A for the synthesis of the visual chromophore and the light-sensing pigments has been studied in vertebrate and invertebrate model organisms. To identify the molecular mechanisms that orchestrate the ocular response to vitamin A deprivation, we took advantage of the fact that Drosophila melanogaster predominantly requires vitamin A for vision, but not for development or survival. We analyzed the impacts of vitamin A deficiency on the morphology, the lipidome, and the proteome of the Drosophila eye. We found that chronic vitamin A deprivation damaged the light-sensing compartments and caused a dramatic loss of visual pigments, but also decreased the molar abundance of most phototransduction proteins that amplify and transduce the visual signal. Unexpectedly, vitamin A deficiency also decreased the abundances of specific subunits of mitochondrial TCA cycle and respiratory chain components but increased the levels of cuticle- and lens-related proteins. In contrast, we found no apparent effects of vitamin A deficiency on the ocular lipidome. In summary, chronic vitamin A deficiency decreases the levels of most components of the visual signaling pathway, but also affects molecular pathways that are not vision-specific and whose mechanistic connection to vitamin A remains to be elucidated.

Published
2022
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7. Shotgun lipidomics and mass spectrometry imaging unveil diversity and dynamics in Gammarus fossarum lipid composition

Author

Tingting Fu, Oskar Knittelfelder, Olivier Geffard, Yohann Clément, Eric Testet, Nicolas Elie, David Touboul, Khedidja Abbaci, Andrej Shevchenko, Jerome Lemoine, Arnaud Chaumot, Arnaud Salvador, Davide Degli-Esposti, and Sophie Ayciriex

Subjects
Environmental Science, Lipidomics, Metabolomics, Pollution, Zoology, Science
Abstract

Summary: Sentinel species are playing an indispensable role in monitoring environmental pollution in aquatic ecosystems. Many pollutants found in water prove to be endocrine disrupting chemicals that could cause disruptions in lipid homeostasis in aquatic species. A comprehensive profiling of the lipidome of these species is thus an essential step toward understanding the mechanism of toxicity induced by pollutants. Both the composition and spatial distribution of lipids in freshwater crustacean Gammarus fossarum were extensively examined herein. The baseline lipidome of gammarids of different sex and reproductive stages was established by high throughput shotgun lipidomics. Spatial lipid mapping by high resolution mass spectrometry imaging led to the discovery of sulfate-based lipids in hepatopancreas and their accumulation in mature oocytes. A diverse and dynamic lipid composition in G. fossarum was uncovered, which deepens our understanding of the biochemical changes during development and which could serve as a reference for future ecotoxicological studies.

Published
2021
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8. Neuronal Cholesterol Accumulation Induced by Cyp46a1 Down-Regulation in Mouse Hippocampus Disrupts Brain Lipid Homeostasis

Author

Sophie Ayciriex, Fathia Djelti, Sandro Alves, Anne Regazzetti, Mathieu Gaudin, Jennifer Varin, Dominique Langui, Ivan Bièche, Eloise Hudry, Delphine Dargère, Patrick Aubourg, Nicolas Auzeil, Olivier Laprévote, and Nathalie Cartier

Subjects
neurodegeneration, gene silencing, Cyp46a1, cholesterol, lipidomics, lipid dysregulation, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Impairment in cholesterol metabolism is associated with many neurodegenerative disorders including Alzheimer's disease (AD). However, the lipid alterations underlying neurodegeneration and the connection between altered cholesterol levels and AD remains not fully understood. We recently showed that cholesterol accumulation in hippocampal neurons, induced by silencing Cyp46a1 gene expression, leads to neurodegeneration with a progressive neuronal loss associated with AD-like phenotype in wild-type mice. We used a targeted and non-targeted lipidomics approach by liquid chromatography coupled to high-resolution mass spectrometry to further characterize lipid modifications associated to neurodegeneration and cholesterol accumulation induced by CYP46A1 inhibition. Hippocampus lipidome of normal mice was profiled 4 weeks after cholesterol accumulation due to Cyp46a1 gene expression down-regulation at the onset of neurodegeneration. We showed that major membrane lipids, sphingolipids and specific enzymes involved in phosphatidylcholine and sphingolipid metabolism, were rapidly increased in the hippocampus of AAV-shCYP46A1 injected mice. This lipid accumulation was associated with alterations in the lysosomal cargoe, accumulation of phagolysosomes and impairment of endosome-lysosome trafficking. Altogether, we demonstrated that inhibition of cholesterol 24-hydroxylase, key enzyme of cholesterol metabolism leads to a complex dysregulation of lipid homeostasis. Our results contribute to dissect the potential role of lipids in severe neurodegenerative diseases like AD.

Published
2017
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9. Ceramides and sphingomyelinases in senile plaques

Author

Maï Panchal, Mathieu Gaudin, Adina N. Lazar, Elisa Salvati, Isabelle Rivals, Sophie Ayciriex, Luce Dauphinot, Delphine Dargère, Nicolas Auzeil, Massimo Masserini, Olivier Laprévote, and Charles Duyckaerts

Subjects
Alzheimer disease, Senile plaques, Laser microdissection, Lipidomics, Mass spectrometry, Ceramides, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

The senile plaque is a hallmark lesion of Alzheimer disease (AD). We compared, without a priori, the lipidome of the senile plaques and of the adjacent plaque-free neuropil. The analysis by liquid chromatography coupled with electrospray ionization mass spectrometry revealed that laser microdissected senile plaques were enriched in saturated ceramides Cer(d18:1/18:0) and Cer(d18:1/20:0) by 33 and 78% respectively with respect to the surrounding neuropil. This accumulation of ceramides was not explained by their affinity for Aβ deposits: no interaction between ceramide-liposomes and Aβ fibrils was observed in vitro by surface plasmon resonance and fluorescent ceramide-liposomes showed no affinity for the senile plaques in AD brain tissue. Accumulation of ceramides could be, at least partially, the result of a local production by acid and neutral sphingomyelinases that we found to be present in the corona of the senile plaques.

Published
2014
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10. OS-074 N-acetyl-phenylalanine, a new metabolite derived from the intestinal microbiota participating in hepatic steatosis by altering ER-mitochondria communication

Author

Caussy, Cyrielle, primary, Lefebvre, Rémy, additional, Bendridi, Nadia, additional, Stéphanie, Chanon, additional, Alexandre, Humbert, additional, Delphine, Arquier, additional, Sophie, Ayciriex, additional, Nicolas, Bertocchini, additional, Nawrot, Margaux, additional, Aurélie, Vielle-Marchiset, additional, Bruno, Pillot, additional, Claudie, Pinteur, additional, Loomba, Rohit, additional, and Rieusset, Jennifer, additional

Published
2024
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11. Challenges and perspectives in MS-based omics approaches for ecotoxicology studies: An insight on Gammarids sentinel amphipods

Author

Valentina Calabrese, Arnaud Salvador, Yohann Clément, Thomas Alexandre Brunet, Anabelle Espeyte, Arnaud Chaumot, Olivier Geffard, Davide Degli-Esposti, and Sophie Ayciriex

Abstract

The aquatic environment is one of the most complex biosystems, as organism at all trophic levels may be exposed to a multitude of pollutants. As major goals, ecotoxicology typically investigates the impact of toxic pollutants on the ecosystems through the study of sentinel organisms. Over the past decades, Mass Spectrometry (MS)-based omics approaches have been extended to sentinel species both in laboratory and field exposure conditions. Single-omics approaches enable the discovery of biomarkers mirroring the health status of an organism. By covering a restricted set of the molecular cascade, they turn out to only partially satisfy the understanding of complex ecotoxicological effects. In contrast, a more complete understanding of the ecotoxicity pathways can be accessed through multi-omics approaches. In this perspective, we provide a state-of-the-art and a critical evaluation on further developments in MS-based single and multi-omics studies in aquatic ecotoxicology. As case example, literature regarding Gammarids freshwater amphipods, non-model sentinel organisms sensitive to pollutants and environmental changes and crucial species for downstream ecosystems, will be reviewed.

Published
2023
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15. Development of a multi-omics extraction method for ecotoxicology: investigation of the reproductive cycle of Gammarus fossarum

Author

Julien Faugere, Thomas Alexandre Brunet, Yohann Clément, Anabelle Espeyte, Olivier Geffard, Jérôme Lemoine, Arnaud Chaumot, Davide Degli-Esposti, Sophie Ayciriex, and Arnaud Salvador

Subjects
Analytical Chemistry
Abstract

Omics study exemplified by proteomics, lipidomics or metabolomics, provides the opportunity to get insight of the molecular modifications occurring in living organisms in response to contaminants or in different physiological conditions. However, individual omics discloses only a single layer of information leading to a partial image of the biological complexity. Multiplication of samples preparation and processing can generate analytical variations resulting from several extractions and instrumental runs. To get all the -omics information at the proteins, metabolites and lipids level coming from a unique sample, a specific sample preparation must be optimized. In this study, we streamlined a biphasic extraction procedure based on a MTBE/Methanol mixture to provide the simultaneous extraction of polar (proteins, metabolites) and apolar compounds (lipids) for multi-omics analyses from a unique biological sample by a liquid chromatography (LC)/mass spectrometry (MS)/MS-based targeted approach. We applied the methodology for the study of female amphipod Gammarus fossarum during the reproductive cycle. Multivariate data analyses including Partial Least Squares Discriminant Analysis and multiple factor analysis were applied for the integration of the multi-omics data sets and highlighted molecular signatures, specific to the different stages.

Published
2023
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16. Multiple reaction monitoring mass spectrometry for the discovery of environmentally modulated proteins in an aquatic invertebrate sentinel species, Gammarus fossarum

Author

Maxime Leprêtre, Olivier Geffard, Anabelle Espeyte, Julien Faugere, Sophie Ayciriex, Arnaud Salvador, Nicolas Delorme, Arnaud Chaumot, and Davide Degli-Esposti

Subjects
Male, History, Polymers and Plastics, Health, Toxicology and Mutagenesis, Fresh Water, General Medicine, Toxicology, Pollution, Industrial and Manufacturing Engineering, Mass Spectrometry, Sentinel Species, Animals, Amphipoda, Business and International Management, Biomarkers, Environmental Monitoring
Abstract

Multiple reaction monitoring (MRM) mass spectrometry is emerging as a relevant tool for measuring customized molecular markers in freshwater sentinel species. While this technique is typically used for the validation of protein molecular markers preselected from shotgun experiments, recent gains of MRM multiplexing capacity offer new possibilities to conduct large-scale screening of animal proteomes. By combining the strength of active biomonitoring strategies and MRM technologies, this study aims to propose a new strategy for the discovery of candidate proteins that respond to environmental variability. For this purpose, 249 peptides derived from 147 proteins were monitored by MRM in 273 male gammarids caged in 56 environmental sites, representative of the diversity of French water bodies. A methodology is here proposed to identify a set of customized housekeeping peptides (HKPs) used to correct analytical batch effects and allow proper comparison of peptide levels in gammarids. A comparative analysis performed on HKPs-normalized data resulted in the identification of peptides highly modulated in the environment and derived from proteins likely involved in the environmental stress response. Overall, this study proposes a breakthrough approach to screen and identify potential proteins responding to relevant environmental conditions in sentinel species.

Published
2022
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17. Biallelic variants in

Author

Kyle, Thompson, Lucas, Bianchi, Francesca, Rastelli, Florence, Piron-Prunier, Sophie, Ayciriex, Claude, Besmond, Laurence, Hubert, Magalie, Barth, Inês A, Barbosa, Charu, Deshpande, Manali, Chitre, Sarju G, Mehta, Eric J M, Wever, Pascale, Marcorelles, Sandra, Donkervoort, Dimah, Saade, Carsten G, Bönnemann, Katherine R, Chao, Chunyu, Cai, Susan T, Iannaccone, Andrew F, Dean, Robert, McFarland, Frédéric M, Vaz, Agnès, Delahodde, Robert W, Taylor, and Agnès, Rötig

Abstract

Mitochondrial disorders are clinically and genetically heterogeneous, with variants in mitochondrial or nuclear genes leading to varied clinical phenotypes.

Published
2021

18. Shotgun lipidomics and mass spectrometry imaging unveil diversity and dynamics in Gammarus fossarum lipid composition

Author

Khedidja Abbaci, Olivier Geffard, Sophie Ayciriex, Andrej Shevchenko, David Touboul, Arnaud Chaumot, Jérôme Lemoine, Davide Degli-Esposti, Yohann Clément, Tingting Fu, Eric Testet, Nicolas Elie, Oskar Knittelfelder, Arnaud Salvador, ANABIO-MS - Analyse biomoléculaire par spectrométrie de masse - Biological Analysis by Mass Spectrometry, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute of Molecular Cell Biology and Genetics, Chemometrics and Theoretical Chemistry - Chimiométrie et chimie théorique, Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Riverly (Riverly), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by the French National Research Agency (ANR) (young investigator grant, ANR-18-CE34-0008 PLAN-TOX ), the Chemistry Institute of Lyon (young investigator inter-laboratory cooperation grant, ICL-2017 DOSAGE ), the ISA research funds grant, and also the French GDR 'Aquatic Ecotoxicology' framework which aims at fostering stimulating discussions and collaborations for more integrative approaches. MALDI-TOF instrument at CNRS-ICSN was founded by the Région Ile-de-France (DIM Analytics)., and ANR-18-CE34-0008,PLAN-TOX,Approches Protéomique et Lipidomique pour la compréhension des mécanismes moléculaires de toxicité en lien avec l'altération du métabolisme lipidique chez l'espèce sentinelle Gammarus fossarum durant le cycle de reproduction(2018)

Subjects
0301 basic medicine, STRUCTURAL-CHARACTERIZATION, Sentinel species, Environmental pollution, 02 engineering and technology, Article, Mass spectrometry imaging, CLASSIFICATION, 03 medical and health sciences, Metabolomics, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Lipidomics, [CHIM]Chemical Sciences, 14. Life underwater, lcsh:Science, ACCUMULATION, NM ULTRAVIOLET PHOTODISSOCIATION, Multidisciplinary, Aquatic ecosystem, CRAB, Shotgun lipidomics, MS, Lipidome, 021001 nanoscience & nanotechnology, OVARIAN MATURATION, CRUDE EXTRACTS, Pollution, 030104 developmental biology, Biochemistry, CRUSTACEA, 13. Climate action, [SDE]Environmental Sciences, Environmental Science, lcsh:Q, 0210 nano-technology, Zoology, AMPHIPODA
Abstract

Summary Sentinel species are playing an indispensable role in monitoring environmental pollution in aquatic ecosystems. Many pollutants found in water prove to be endocrine disrupting chemicals that could cause disruptions in lipid homeostasis in aquatic species. A comprehensive profiling of the lipidome of these species is thus an essential step toward understanding the mechanism of toxicity induced by pollutants. Both the composition and spatial distribution of lipids in freshwater crustacean Gammarus fossarum were extensively examined herein. The baseline lipidome of gammarids of different sex and reproductive stages was established by high throughput shotgun lipidomics. Spatial lipid mapping by high resolution mass spectrometry imaging led to the discovery of sulfate-based lipids in hepatopancreas and their accumulation in mature oocytes. A diverse and dynamic lipid composition in G. fossarum was uncovered, which deepens our understanding of the biochemical changes during development and which could serve as a reference for future ecotoxicological studies., Graphical Abstract, Highlights • Baseline lipidome profiling of G. fossarum of different sex and reproductive stages • Spatial localization of lipids in gammarid tissue by mass spectrometry imaging • SIMS imaging guided discovery of sulfate-based lipids in hepatopancreas epithelium • Disclosure of a dynamic lipid composition in maturing female oocytes, Environmental Science; Lipidomics; Metabolomics; Pollution; Zoology

Published
2021
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19. Shotgun Lipidomics and Mass Spectrometry Imaging Unveil Diversity and Dynamics in Lipid Composition in Gammarus Fossarum

Author

Yohann Clément, Khedidja Abbaci, Olivier Geffard, Sophie Ayciriex, Tingting Fu, Andrej Shevchenko, Nicolas Elie, Arnaud Chaumot, Oskar Knittelfelder, Jérôme Lemoine, Eric Testet, David Touboul, Davide Degli-Esposti, Arnaud Salvador, Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pollutant, 0303 health sciences, biology, Sentinel species, Aquatic ecosystem, [SDV]Life Sciences [q-bio], 010401 analytical chemistry, Zoology, Environmental pollution, Shotgun lipidomics, Lipidome, biology.organism_classification, 01 natural sciences, Mass spectrometry imaging, 0104 chemical sciences, 03 medical and health sciences, 13. Climate action, [CHIM]Chemical Sciences, Hepatopancreas, 14. Life underwater, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

SummarySentinel species are playing an indispensable role in monitoring environmental pollution in aquatic ecosystems. Many pollutants found in water prove to be endocrine disrupting chemicals that could cause disruptions in lipid homeostasis in aquatic species. A comprehensive profiling of the lipidome of these species is thus an essential step towards understanding the mechanism of toxicity induced by pollutants. We here extensively examined both the composition and spatial distribution of lipids in freshwater crustacean Gammarus fossarum. The baseline lipidome of gammarids of different gender and reproductive stage was established by high throughput shotgun lipidomics. Spatial lipid mapping by high resolution mass spectrometry imaging led to the discovery of sulfate-based lipids in hepatopancreas and their accumulation in mature oocytes. We uncovered in G. fossarum a diverse and dynamic lipid composition that deepens our understanding of the biochemical changes during development and which could serve as a reference for future ecotoxicological studies.

Published
2020
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20. In situ isobaric lipid mapping by MALDI-Ion Mobility Separation-Mass Spectrometry Imaging

Author

Arnaud Chaumot, Sophie Ayciriex, Olivier Geffard, Manuel Chapelle, Arnaud Salvador, Matthias Szesny, Yohann Clément, Davide Degli-Esposti, Alexandre Verdu, Janina Oetjen, Tingting Fu, ANABIO-MS - Analyse biomoléculaire par spectrométrie de masse - Biological Analysis by Mass Spectrometry, Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Bruker Daltonics GmbH, RiverLy (UR Riverly), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Chemometrics and Theoretical Chemistry - Chimiométrie et chimie théorique, Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Bruker Daltonik GmbH, Riverly (Riverly), ANR-18-CE34-0008,PLAN-TOX,Approches Protéomique et Lipidomique pour la compréhension des mécanismes moléculaires de toxicité en lien avec l'altération du métabolisme lipidique chez l'espèce sentinelle Gammarus fossarum durant le cycle de reproduction(2018), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and bruker

Subjects
In situ, Ion-mobility spectrometry, [SDV]Life Sciences [q-bio], ion mobility separation, mass spectrometry imaging, 01 natural sciences, Mass spectrometry imaging, Ion, Isomerism, Tandem Mass Spectrometry, Desorption, Ionization, Ion Mobility Spectrometry, Animals, [CHIM]Chemical Sciences, Amphipoda, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MALDI, TIMS, Spectroscopy, ComputingMilieux_MISCELLANEOUS, Chromatography, Molecular Structure, 010405 organic chemistry, Chemistry, 010401 analytical chemistry, lipid isomers, Biological tissue, Lipids, 0104 chemical sciences, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, [SDE]Environmental Sciences, Isobaric process, Female, [CHIM.OTHE]Chemical Sciences/Other
Abstract

note d'application; International audience; The highly diverse chemical structures of lipids make their analysis directly from biological tissue sections extremely challenging. Here, we report the in situ mapping and identification of lipids in a freshwater crustaceanGammarus fossarumusing matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) in combination with an additional separation dimension using ion mobility spectrometry (IMS). The high-resolution trapped ion mobility spectrometry (TIMS) allowed efficient separation of isobaric/isomeric lipids showing distinct spatial distributions. The structures of the lipids were further characterized by MS/MS analysis. It is demonstrated that MALDI MSI with mobility separation is a powerful tool for distinguishing and localizing isobaric/isomeric lipids.

Published
2020
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21. Scout-multiple reaction monitoring: A liquid chromatography tandem mass spectrometry approach for multi-residue pesticide analysis without time scheduling

Author

Arnaud Salvador, Christelle Margoum, Yves Leblanc, Romain Carrière, Sophie Ayciriex, Jérôme Lemoine, ANABIO-MS - Analyse biomoléculaire par spectrométrie de masse - Biological Analysis by Mass Spectrometry, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Riverly (Riverly), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SCIEX, Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), and Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)

Subjects
Scheduling (production processes), 010402 general chemistry, 01 natural sciences, Biochemistry, Analytical Chemistry, Liquid chromatography–mass spectrometry, Robustness (computer science), [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Tandem Mass Spectrometry, sMRM: scheduled multiple reaction monitoring, Calibration, [CHIM]Chemical Sciences, MRM: multiple reaction monitoring, Scout-MRM, Multiplexing capability, Retention time independency, ComputingMilieux_MISCELLANEOUS, Chromatography, Chemistry, 010401 analytical chemistry, Organic Chemistry, Selected reaction monitoring, Pesticide Residues, General Medicine, Pesticide, 0104 chemical sciences, Targeted mass spectrometry, Proof of concept, [SDE]Environmental Sciences, Biological system, Chromatography, Liquid
Abstract

The authors thank David Cox from SCIEX for developing the Scout-MRM software patch and Matthieu le Dréau from INRAE for pesticide quantification.; International audience; In this work, an innovative method is described for multi-residue pesticide analysis by liquid chromatography coupled to targeted mass spectrometry, called "Scout-MRM, this new acquisition mode relies on the monitoring by either endogenous or spiked Scout compounds, hence fully releasing the monitoring of target molecules from time scheduling. As a proof of concept, a Scout-MRM method was built where 5 transitions groups tracking a total of 191 pesticides where successively triggered under the control of 5 spiked-in deuterated pesticides. As expected from its retention time independency, Scout-MRM demonstrates strong detection robustness towards modifications of gradient parameters, as well as easy method transfer between distinct analytical platforms with nearly 100% recovery after a single run. Finally, Scout-MRM was used for the multi-residue screening and quantification of pesticides in real surface water samples, by applying an external calibration procedure and comparing it with classical scheduled reaction monitoring methods. (C) 2020 Elsevier B.V. All rights reserved.

Published
2019
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22. The lipidome associated with the γ-secretase complex is required for its integrity and activity

Author

Andrej Shevchenko, Mohamed Chami, Sophie Ayciriex, Hermeto Gerber, Henning Stahlberg, Guillermo M. Garcia Osuna, Patrick C. Fraering, Université Paris Descartes - Faculté de Pharmacie de Paris ( UPD5 Pharmacie ), Université Paris Descartes - Paris 5 ( UPD5 ), Max Planck Institute for Cell Biology and Genetics, Max-Planck-Institut, Institut des Sciences Analytiques ( ISA ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon, Laboratoire d'océanographie de Villefranche ( LOV ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Max Planck Institute of Molecular Cell Biology and Genetics ( MPI-CBG ), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Laboratoire d'océanographie de Villefranche (LOV), Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Faculté de Pharmacie de Paris - Université Paris Descartes (UPD5 Pharmacie), and Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.medical_treatment, Biochemistry, Substrate Specificity, lipid microenvironment, Amyloid beta-Protein Precursor, chemistry.chemical_compound, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], lipid species, APH-1, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], ComputingMilieux_MISCELLANEOUS, gamma-secretase, intramembrane-cleaving protease, mass spectrometry, chemistry.chemical_classification, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Lipidome, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Intramembrane protease, Proteolipids, Biology, 03 medical and health sciences, proteoliposomes, Alzheimer Disease, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Phosphatidylcholine, medicine, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, Gamma secretase, quantitative shotgun lipidomics, Protease, Cholesterol, Cell Biology, Lipid Metabolism, 030104 developmental biology, Enzyme, chemistry, biology.protein, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry, Amyloid Precursor Protein Secretases, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

gamma-Secretase is a multi-subunit membrane protease complex that catalyses the final intramembrane cleavage of the beta-amyloid precursor protein (APP) during the neuronal production of amyloid-beta peptides (A beta), which are implicated as the causative agents of Alzheimer's disease (AD). In the present study, we report the reconstitution of a highly purified, active gamma-secretase complex into proteoliposomes without exogenous lipids and provide the first direct evidence for the existence of a microenvironment of 53 molecular species from 11 major lipid classes specifically associated with the gamma-secretase complex, including phosphatidylcholine and cholesterol. Importantly, we demonstrate that the pharmacological modulation of certain phospholipids abolishes both the integrity and the enzymatic activity of the intramembrane protease. Together, our findings highlight the importance of a specific lipid microenvironment for the structure and function of gamma-secretase.

Published
2016
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23. On-Line Solid Phase Extraction Liquid Chromatography-Mass Spectrometry Method for Multiplexed Proteins Quantitation in an Ecotoxicology Test Specie: Gammarus fossarum

Author

Duarte Gouveia, Christine Almunia, Sophie Ayciriex, Aurore Charnot, Geffard Olivier, Jérôme Lemoine, Arnaud Salvador, Arnaud Chaumot, Jean Armengaud, ANABIO-MS - Analyse biomoléculaire par spectrométrie de masse - Biological Analysis by Mass Spectrometry, Institut des Sciences Analytiques (ISA), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Milieux aquatiques, écologie et pollutions (UR MALY), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Laboratoire Innovations technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), The authors acknowledge the French 'Ministère de la recherche et de l’enseignement supérieur', the ANR program 'ProteoGam' (ANR-14-CE21-0006-02) and the Regional Water Agency Rhône-Méditerranée-Corse for financial support., ANR-14-CE21-0006,ProteoGam,Protéomique pour de nouveaux biomarqueurs en écotoxicologie chez les gammares: challenge de la biodiversité et immunoanalyse multiplexée comme outil de diagnostic(2014), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, protein quantification, lcsh:RS1-441, Mass spectrometry, ecotoxicology, lcsh:Pharmacy and materia medica, lcsh:Chemistry, 03 medical and health sciences, Liquid chromatography–mass spectrometry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Ecotoxicology, [CHIM]Chemical Sciences, Sample preparation, Solid phase extraction, ComputingMilieux_MISCELLANEOUS, mass spectrometry, Chromatography, sample preparation, Chemistry, biomarkers, multiplex, 030104 developmental biology, lcsh:QD1-999, Gammarus fossarum, [SDE]Environmental Sciences
Abstract

OBJECTIVES: A fully automated on-line solid phase extraction procedure was developed and validated for the analysis of 30 key proteins biomarkers in Gammarus fossarum. METHODS: After protein extraction and tryptic digestion, peptides were cleaned-up onto an on-line SPE cartridge (Oasis HLB, 2.1 mmx20 mm, 25 μm particle size) coupled to a LC-MS/MS system. The SRM assay was performed on a quadrupole-trap mass spectrometer. RESULTS: The method targeted 30 proteins in G. fossarum (46 reporter peptides used in the SRM assay) was developed and validated. The method duration was 30 min including the on-line SPE step saving up to 6h per sample. The method’s performance was validated according to FDA guidelines. CONCLUSIONS: Our method substitutes valuably conventional methods like off-line SPE performed beforehand to the LC-MS/MS system. This assay offers higher sensitivity with no loss and/or degradation of reporter peptides and reached good specifications (linearity, precision and accuracy).

Published
2018
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24. Scout-MRM: Multiplexed Targeted Mass Spectrometry-Based Assay without Retention Time Scheduling Exemplified by Dickeya dadantii Proteomic Analysis during Plant Infection

Author

J. C. Yves Le Blanc, Romain Carrière, Hubert Hondermarck, Jérôme Lemoine, Sébastien Bontemps Gallo, Sophie Ayciriex, Blandine Rougemont, Jean-Marie Lacroix, ANABIO-MS - Analyse biomoléculaire par spectrométrie de masse - Biological Analysis by Mass Spectrometry, Institut des Sciences Analytiques (ISA), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Signalisation des facteurs de croissance dans le cancer du sein. Protéomique fonctionnelle, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), SCIEX Ltd, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS), and SCIEX

Subjects
0301 basic medicine, Proteomics, Dickeya dadantii, Nanotechnology, Computational biology, Multiplexing, Mass Spectrometry, Chicory, Analytical Chemistry, Scheduling (computing), 03 medical and health sciences, Enterobacteriaceae, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Scout-MRM, Chromatography, High Pressure Liquid, Multiplexed Targeted Mass Spectrometry, biology, Chemistry, Selected reaction monitoring, biology.organism_classification, plant infection, Plant Leaves, 030104 developmental biology, Targeted mass spectrometry, Peptides, Retention time, Protein network
Abstract

International audience; Targeted mass spectrometry of a surrogate peptide panel is a powerful method to study the dynamics of protein networks, but chromatographic time scheduling remains a major limitation for dissemination and implementation of robust and large multiplexed assays. We unveil a Multiple Reaction Monitoring method (Scout-MRM) where the use of spiked scout peptides triggers complex transition lists, regardless of the retention time of targeted surrogate peptides. The interest of Scout-MRM method regarding the retention time independency, multiplexing capability, reproducibility, and putative interest in facilitating method transfer was illustrated by a 782-peptide-plex relative assay targeting 445 proteins of the phytopathogen Dickeya dadantii during plant infection.

Published
2017
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25. Ultra performance liquid chromatography - mass spectrometry studies of formalin-induced alterations of human brain lipidome

Author

Alain Brunelle, David Touboul, Nicolas Auzeil, Erwan Werner, Olivier Laprévote, Bernard Walther, Sophie Ayciriex, Charles Duyckaerts, Maï Panchal, Claire Boursier-Neyret, and Mathieu Gaudin

Subjects
Analyte, chemistry.chemical_compound, Chromatography, Biochemistry, Liquid chromatography–mass spectrometry, Chemistry, Lipidomics, Phospholipid, Lipidome, Mass spectrometry, Sphingolipid, Spectroscopy, Triple quadrupole mass spectrometer
Abstract

The development of ‘omics’ sciences offers new opportunities for the study of neurodegenerative diseases but increases at the same time the sample demand on brain banks that collect and store valuable human post-mortem tissue. Our study aims to evaluate in lipidomics the potential of formalin-fixed tissue compared with the cryopreservation method, considered as the gold standard for biochemical research. Two complementary liquid chromatography/mass spectrometry analytical platforms were used on the basis of hybrid quadrupole time-of-flight and triple quadrupole mass spectrometers. Untargeted fingerprinting, semitargeted profiling of specific lipid classes and targeted monitoring of lipid species were performed in formalin-fixed and cryopreserved samples to provide detailed information at the molecular level on the formalin-induced alterations of the brain tissue. In vitro incubations of lipid standards were also performed to further describe the degradation processes induced by formaldehyde. Phospholipid compounds were found to be extensively hydrolysed, whilst the sphingolipid ones were preserved. N-methylation and N-formylation of amine-containing phospholipids have also been evidenced. These findings show that the potential detrimental effect of formalin on the analytes of interest must be taken into account when analysing formalin-fixed samples. Copyright © 2014 John Wiley & Sons, Ltd.

Published
2014
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26. Ceramides and sphingomyelinases in senile plaques

Author

Luce Dauphinot, Maï Panchal, Olivier Laprévote, Massimo Masserini, Isabelle Rivals, Charles Duyckaerts, Adina N. Lazar, Delphine Dargère, Nicolas Auzeil, Sophie Ayciriex, Elisa Salvati, Mathieu Gaudin, Faculté de Pharmacie de Paris - Université Paris Descartes (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Géosciences Marines (GM), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Equipe de Statistique Appliquée (UMRS 1158) (ESA), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire de Neurobiologie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et Toxicologie Analytique et Cellulaire (EA 4463), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Panchal, M, Gaudin, M, Lazar, A, Salvati, E, Rivals, I, Ayciriex, S, Dauphinot, L, Dargère, D, Auzeil, N, Masserini, M, Laprévote, O, Duyckaerts, C, Université Paris Descartes - Faculté de Pharmacie de Paris ( UPD5 Pharmacie ), Université Paris Descartes - Paris 5 ( UPD5 ), Max Planck Institute for Cell Biology and Genetics, Max-Planck-Institut, Institut des Sciences Analytiques ( ISA ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Claude Bernard Lyon 1 ( UCBL ), ICNS - Institut de Chimie des Substances naturelles, Unité de recherche Géosciences Marines (Ifremer) ( GM ), Institut Français de Recherche pour l'Exploitation de la Mer ( IFREMER ), Equipe de Statistique Appliquée ( ESA ), ESPCI ParisTech, ESPCI ParisTech-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Chimie et Toxicologie Analytique et Cellulaire ( EA 4463 ), Institut de Chimie des Substances Naturelles ( ICSN ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Neuropathologie Raymond Escourolle, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Unité de recherche Géosciences Marines (Ifremer) (GM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Equipe de Statistique Appliquée (ESA), ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]

Subjects
Male, Amyloid beta-Peptide, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Plaque, Amyloid, Ceramide, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 0302 clinical medicine, Senile plaques, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Lipid, Middle Aged, Lipidome, BIO/10 - BIOCHIMICA, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Sphingomyelin Phosphodiesterase, medicine.anatomical_structure, Neurology, Biochemistry, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Female, Alzheimer's disease, Alzheimer disease, Sphingomyelin, Microdissection, Human, Electrospray ionization, Fibril, Ceramides, lcsh:RC321-571, 03 medical and health sciences, Apolipoproteins E, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Aβ peptide, Lipidomics, Neuropil, medicine, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Aged, 030304 developmental biology, Amyloid beta-Peptides, Senile plaque, Mass spectrometry, Lipidomic, Surface Plasmon Resonance, medicine.disease, Molecular biology, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry, Sphingomyelinase, Laser microdissection, 030217 neurology & neurosurgery, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Chromatography, Liquid
Abstract

The senile plaque is a hallmark lesion of Alzheimer disease (AD). We compared, without a priori, the lipidome of the senile plaques and of the adjacent plaque-free neuropil. The analysis by liquid chromatography coupled with electrospray ionization mass spectrometry revealed that laser microdissected senile plaques were enriched in saturated ceramides Cer(d18:1/18:0) and Cer(d18:1/20:0) by 33 and 78% respectively with respect to the surrounding neuropil. This accumulation of ceramides was not explained by their affinity for Aβ deposits: no interaction between ceramide-liposomes and Aβ fibrils was observed in vitro by surface plasmon resonance and fluorescent ceramide-liposomes showed no affinity for the senile plaques in AD brain tissue. Accumulation of ceramides could be, at least partially, the result of a local production by acid and neutral sphingomyelinases that we found to be present in the corona of the senile plaques. © 2014 Elsevier Inc.

Published
2014
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27. PSI1 is responsible for the stearic acid enrichment that is characteristic of phosphatidylinositol in yeast

Author

Denis Coulon, René Lessire, Gisèle Velours, Eric Testet, Jean-Jacques Bessoule, Valérie Boyer, Willem Kulik, Sophie Ayciriex, Marina Le Guédard, Christer S. Ejsing, and Andrej Shevchenko

Subjects
Phospholipid, Cell Biology, Biochemistry, Palmitic acid, chemistry.chemical_compound, chemistry, Stearate, Acyltransferase, Saturated fatty acid, Lysophosphatidylinositol, lipids (amino acids, peptides, and proteins), Phosphatidylinositol, Stearic acid, Molecular Biology
Abstract

In yeast, both phosphatidylinositol and phosphatidylserine are synthesized from cytidine diphosphate-diacylglycerol. Because, as in other eukaryotes, phosphatidylinositol contains more saturated fatty acids than phosphatidylserine (and other phospholipids), it has been hypothesized that either phosphatidylinositol is synthesized from distinct cytidine diphosphate-diacylglycerol molecules, or that, after its synthesis, it is modified by a hypothetical acyltransferase that incorporates saturated fatty acid into neo-synthesized molecules of phosphatidylinositol. We used database search methods to identify an acyltransferase that could catalyze such an activity. Among the various proteins that we studied, we found that Psi1p (phosphatidylinositol stearoyl incorporating 1 protein) is required for the incorporation of stearate into phosphatidylinositol because GC and MS analyses of psi1Δ lipids revealed an almost complete disappearance of stearic (but not of palmitic acid) at the sn-1 position of this phospholipid. Moreover, it was found that, whereas glycerol 3-phosphate, lysophosphatidic acid and 1-acyl lysophosphatidylinositol acyltransferase activities were similar in microsomal membranes isolated from wild-type and psi1Δ cells, microsomal membranes isolated from psi1Δ cells are devoid of the sn-2-acyl-1-lysolysophosphatidylinositol acyltransferase activity that is present in microsomal membranes isolated from wild-type cells. Moreover, after the expression of PSI1 in transgenic psi1Δ cells, the sn-2-acyl-1-lysolysophosphatidylinositol acyltransferase activity was recovered, and was accompanied by a strong increase in the stearic acid content of lysophosphatidylinositol. As previously suggested for phosphatidylinositol from animal cells (which contains almost exclusively stearic acid as the saturated fatty acid), the results obtained in the present study demonstrate that the existence of phosphatidylinositol species containing stearic acid in yeast results from a remodeling of neo-synthesized molecules of phosphatidylinositol.

Published
2009
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28. Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology

Author

Kristin Michaelsen-Preusse, Sophie Ayciriex, David Blum, Luc Buée, Marie-Claude Potier, Ivan Bièche, Francisco-Jose Fernandez-Gomez, Fathia Djelti, Luce Dauphinot, Jérôme Braudeau, Raphaëlle Caillierez, Nathalie Cartier, Marie-Anne Burlot, Olivier Laprévote, Benoit Gautier, Patrick Dutar, Martin Korte, Mickael Audrain, Brigitte Potier, Nicolas Auzeil, Jennifer Varin, Faculté de Pharmacie de Paris - Université Paris Descartes (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Zoological Institute, Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig], Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, physiopathologie et approches thérapeutiques des maladies héréditaires du système nerveux (EA 7331), Inserm U986, Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes adaptatifs : des organismes aux communautés, Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Alzheimer & Tauopathies [JPArc], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Facultés des sciences pharmaceutiques et biologiques, Laboratoire de Chimie et Toxicologie Analytique et Cellulaire (EA 4463), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Descartes - Faculté de Pharmacie de Paris ( UPD5 Pharmacie ), Université Paris Descartes - Paris 5 ( UPD5 ), Max Planck Institute for Cell Biology and Genetics, Max-Planck-Institut, Institut des Sciences Analytiques ( ISA ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Claude Bernard Lyon 1 ( UCBL ), Thérapie génique, Génomique et Epigénomique ( U 1169 ), Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Technische Universität Braunschweig [Braunschweig], Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique, physiopathologie et approches thérapeutiques des maladies héréditaires du système nerveux ( EA 7331 ), Institut National de la Santé et de la Recherche Médicale, Mécanismes adaptatifs : des organismes aux communautés ( MECADEV ), Muséum National d'Histoire Naturelle ( MNHN ) -Centre National de la Recherche Scientifique ( CNRS ), Alzheimer & Tauopathies ( Equipe 1 ), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ) -Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172 ( JPArc ), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Institut de Chimie des Substances Naturelles ( ICSN ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Chimie et Toxicologie Analytique et Cellulaire ( EA 4463 ), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique ( CNRS ), Department of Cellular and Systems Neurobiology, Max-Planck-Institut für Neurobiologie, Service MIRCEN ( MIRCEN ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Alzheimer & Tauopathies (Equipe 1), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and Université Paris-Saclay-Institut de Biologie François JACOB (JACOB)

Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hippocampus, Mice, chemistry.chemical_compound, 0302 clinical medicine, Cerebrospinal fluid, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Gliosis, Phosphorylation, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, medicine.anatomical_structure, Tauopathies, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Alzheimer's disease, medicine.symptom, medicine.medical_specialty, Amyloid, Central nervous system, Mice, Transgenic, tau Proteins, Biology, 03 medical and health sciences, Alzheimer Disease, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Cholesterol 24-Hydroxylase, Genetics, medicine, Animals, Humans, Cholesterol 24-hydroxylase, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, 030304 developmental biology, Memory Disorders, Cholesterol, medicine.disease, Hydroxycholesterols, Disease Models, Animal, Endocrinology, chemistry, Steroid Hydroxylases, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry, 030217 neurology & neurosurgery, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

Alzheimer's disease (AD) is characterized by both amyloid and Tau pathologies. The amyloid component and altered cholesterol metabolism are closely linked, but the relationship between Tau pathology and cholesterol is currently unclear. Brain cholesterol is synthesized in situ and cannot cross the blood-brain barrier: to be exported from the central nervous system into the blood circuit, excess cholesterol must be converted to 24S-hydroxycholesterol by the cholesterol 24-hydroxylase encoded by the CYP46A1 gene. In AD patients, the concentration of 24S-hydroxycholesterol in the plasma and the cerebrospinal fluid are lower than in healthy controls. The THY-Tau22 mouse is a model of AD-like Tau pathology without amyloid pathology. We used this model to investigate the potential association between Tau pathology and CYP46A1 modulation. The amounts of CYP46A1 and 24S-hydroxycholesterol in the hippocampus were lower in THY-Tau22 than control mice. We used an adeno-associated virus (AAV) gene transfer strategy to increase CYP46A1 expression in order to investigate the consequences on THY-Tau22 mouse phenotype. Injection of the AAV-CYP46A1 vector into the hippocampus of THY-Tau22 mice led to CYP46A1 and 24S-hydroxycholesterol content normalization. The cognitive deficits, impaired long-term depression and spine defects that characterize the THY-Tau22 model were completely rescued, whereas Tau hyperphosphorylation and associated gliosis were unaffected. These results argue for a causal link between CYP46A1 protein content and memory impairments that result from Tau pathology. Therefore, CYP46A1 may be a relevant therapeutic target for Tauopathies and especially for AD.

Published
2015
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29. CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer’s disease

Author

Dominique Langui, Michel Vidaud, Eloise Hudry, Nathalie Cartier, Ivan Bièche, Marc Dhenain, Sandro Alves, Olivier Laprévote, Patrick Aubourg, Sophie Ayciriex, Charles Duyckaerts, Jérôme Braudeau, Catherine Marquer, Nicolas Auzeil, Farah Chali, Marie-Claude Potier, Richard B. Miles, Fathia Djelti, Jennifer Varin, Faculté de Pharmacie de Paris - Université Paris Descartes (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Mécanismes adaptatifs : des organismes aux communautés, Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Génétique, physiopathologie et approches thérapeutiques des maladies héréditaires du système nerveux (EA 7331), Facultés des sciences pharmaceutiques et biologiques, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et Toxicologie Analytique et Cellulaire (EA 4463), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Inserm U986, Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Faculté de Pharmacie de Paris ( UPD5 Pharmacie ), Université Paris Descartes - Paris 5 ( UPD5 ), Max Planck Institute for Cell Biology and Genetics, Max-Planck-Institut, Institut des Sciences Analytiques ( ISA ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Claude Bernard Lyon 1 ( UCBL ), Mécanismes adaptatifs : des organismes aux communautés ( MECADEV ), Muséum National d'Histoire Naturelle ( MNHN ) -Centre National de la Recherche Scientifique ( CNRS ), Thérapie génique, Génomique et Epigénomique ( U 1169 ), Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Laboratoire des Maladies Neurodégénératives - UMR 9199 ( LMN ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Génétique, physiopathologie et approches thérapeutiques des maladies héréditaires du système nerveux ( EA 7331 ), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Toxicologie, Pharmacologie et Signalisation Cellulaire ( U1124 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Chimie et Toxicologie Analytique et Cellulaire ( EA 4463 ), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut de Chimie des Substances Naturelles ( ICSN ), Centre National de la Recherche Scientifique ( CNRS ), Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux ( Inserm U745 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Neuropathologie Raymond Escourolle, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut National de la Santé et de la Recherche Médicale, Service MIRCEN ( MIRCEN ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hippocampus, Hippocampal formation, Small hairpin RNA, chemistry.chemical_compound, Amyloid beta-Protein Precursor, 0302 clinical medicine, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], RNA interference, Homeostasis, Enzyme Inhibitors, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Lipid raft, ComputingMilieux_MISCELLANEOUS, Neurons, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Neurodegeneration, Brain, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Cholesterol, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Female, medicine.medical_specialty, Mice, Transgenic, Biology, 03 medical and health sciences, Alzheimer Disease, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Cholesterol 24-Hydroxylase, Animals, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Liver X receptor, 030304 developmental biology, Amyloid beta-Peptides, medicine.disease, Mice, Inbred C57BL, Endocrinology, chemistry, Steroid Hydroxylases, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry, Neurology (clinical), Neuroscience, 030217 neurology & neurosurgery, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

Abnormalities in neuronal cholesterol homeostasis have been suspected or observed in several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and Huntington's disease. However, it has not been demonstrated whether an increased abundance of cholesterol in neurons in vivo contributes to neurodegeneration. To address this issue, we used RNA interference methodology to inhibit the expression of cholesterol 24-hydroxylase, encoded by the Cyp46a1 gene, in the hippocampus of normal mice. Cholesterol 24-hydroxylase controls cholesterol efflux from the brain and thereby plays a major role in regulating brain cholesterol homeostasis. We used an adeno-associated virus vector encoding short hairpin RNA directed against the mouse Cyp46a1 mRNA to decrease the expression of the Cyp46a1 gene in hippocampal neurons of normal mice. This increased the cholesterol concentration in neurons, followed by cognitive deficits and hippocampal atrophy due to apoptotic neuronal death. Prior to neuronal death, the recruitment of the amyloid protein precursor to lipid rafts was enhanced leading to the production of β-C-terminal fragment and amyloid-β peptides. Abnormal phosphorylation of tau and endoplasmic reticulum stress were also observed. In the APP23 mouse model of Alzheimer's disease, the abundance of amyloid-β peptides increased following inhibition of Cyp46a1 expression, and neuronal death was more widespread than in normal mice. Altogether, these results suggest that increased amounts of neuronal cholesterol within the brain may contribute to inducing and/or aggravating Alzheimer's disease.

Published
2015
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30. Stimulation, Inhibition, or Stabilization of Na,K-ATPase Caused by Specific Lipid Interactions at Distinct Sites

Author

Einat Kapri-Pardes, Sophie Ayciriex, Adriana Katz, Haruo Ogawa, Michael Habeck, Chikashi Toyoshima, Steven J.D. Karlish, Andrej Shevchenko, Haim Haviv, Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Université Paris Descartes - Faculté de Pharmacie de Paris ( UPD5 Pharmacie ), Université Paris Descartes - Paris 5 ( UPD5 ), Max Planck Institute for Cell Biology and Genetics, Max-Planck-Institut, Institut des Sciences Analytiques ( ISA ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Claude Bernard Lyon 1 ( UCBL ), and Max Planck Institute of Molecular Cell Biology and Genetics ( MPI-CBG )

Subjects
Membrane lipids, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Phospholipid, Phosphatidylserines, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 0302 clinical medicine, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Membrane Biology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, Na+/K+-ATPase, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Molecular Biology, Phospholipids, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Phosphatidylethanolamine, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Membrane Proteins, Cell Biology, Phosphatidylserine, Membrane transport, Phosphoproteins, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Cholesterol, Membrane protein, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry, lipids (amino acids, peptides, and proteins), Sodium-Potassium-Exchanging ATPase, Sphingomyelin, 030217 neurology & neurosurgery, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

The activity of membrane proteins such as Na,K-ATPase depends strongly on the surrounding lipid environment. Interactions can be annular, depending on the physical properties of the membrane, or specific with lipids bound in pockets between transmembrane domains. This paper describes three specific lipid-protein interactions using purified recombinant Na,K-ATPase. (a) Thermal stability of the Na,K-ATPase depends crucially on a specific interaction with 18:0/18:1 phosphatidylserine (1-stearoyl-2-oleoyl-sn-glycero-3-phospho-l-serine; SOPS) and cholesterol, which strongly amplifies stabilization. We show here that cholesterol associates with SOPS, FXYD1, and the α subunit between trans-membrane segments αTM8 and -10 to stabilize the protein. (b) Polyunsaturated neutral lipids stimulate Na,K-ATPase turnover by >60%. A screen of the lipid specificity showed that 18:0/20:4 and 18:0/22:6 phosphatidylethanolamine (PE) are the optimal phospholipids for this effect. (c) Saturated phosphatidylcholine and sphingomyelin, but not saturated phosphatidylserine or PE, inhibit Na,K-ATPase activity by 70–80%. This effect depends strongly on the presence of cholesterol. Analysis of the Na,K-ATPase activity and E1-E2 conformational transitions reveals the kinetic mechanisms of these effects. Both stimulatory and inhibitory lipids poise the conformational equilibrium toward E2, but their detailed mechanisms of action are different. PE accelerates the rate of E1 → E2P but does not affect E2(2K)ATP → E13NaATP, whereas sphingomyelin inhibits the rate of E2(2K)ATP → E13NaATP, with very little effect on E1 → E2P. We discuss these lipid effects in relation to recent crystal structures of Na,K-ATPase and propose that there are three separate sites for the specific lipid interactions, with potential physiological roles to regulate activity and stability of the pump.

Published
2015
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31. Production of systemically circulating Hedgehog by the intestine couples nutrition to growth and development

Author

Sophie Ayciriex, Oksana Lavrynenko, Andrej Shevchenko, Maria da Gloria Carvalho, Jonathan Rodenfels, Julio L. Sampaio, Suzanne Eaton, Université Paris Descartes - Faculté de Pharmacie de Paris ( UPD5 Pharmacie ), Université Paris Descartes - Paris 5 ( UPD5 ), Max Planck Institute for Cell Biology and Genetics, Max-Planck-Institut, Institut des Sciences Analytiques ( ISA ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon, Laboratoire de Physico-Chimie des Surfaces ( LPCS ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ), Max Planck Institute of Molecular Cell Biology and Genetics ( MPI-CBG ), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Laboratoire de Physico-Chimie des Surfaces (LPCS), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), and Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Fat body, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Signaling proteins, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, Genetics, medicine, Animals, Endocrine system, Hedgehog Proteins, Nutritional Physiological Phenomena, Intestinal Mucosa, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Hedgehog, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Ecdysteroid, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, Lipid metabolism, Prothoracic gland, biology.organism_classification, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Cell biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Drosophila melanogaster, Endocrinology, chemistry, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Larva, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry, Developmental biology, 030217 neurology & neurosurgery, Developmental Biology, Hormone, Drosophila larvae, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

In Drosophila larvae, growth and developmental timing are regulated by nutrition in a tightly coordinated fashion. The networks that couple these processes are far from understood. Here, we show that the intestine responds to nutrient availability by regulating production of a circulating lipoprotein-associated form of the signaling protein Hedgehog (Hh). Levels of circulating Hh tune the rates of growth and developmental timing in a coordinated fashion. Circulating Hh signals to the fat body to control larval growth. It regulates developmental timing by controlling ecdysteroid production in the prothoracic gland. Circulating Hh is especially important during starvation, when it is also required for mobilization of fat body triacylglycerol (TAG) stores. Thus, we demonstrate that Hh, previously known only for its local morphogenetic functions, also acts as a lipoprotein-associated endocrine hormone, coordinating the response of multiple tissues to nutrient availability.

Published
2014
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32. Ultra performance liquid chromatography - mass spectrometry studies of formalin-induced alterations of human brain lipidome

Author

Mathieu, Gaudin, Maï, Panchal, Sophie, Ayciriex, Erwan, Werner, Alain, Brunelle, David, Touboul, Claire, Boursier-Neyret, Nicolas, Auzeil, Bernard, Walther, Charles, Duyckaerts, and Olivier, Laprévote

Subjects
Brain Chemistry, Cryopreservation, Principal Component Analysis, Tissue Fixation, Formaldehyde, Humans, Lipids, Chromatography, High Pressure Liquid, Mass Spectrometry
Abstract

The development of 'omics' sciences offers new opportunities for the study of neurodegenerative diseases but increases at the same time the sample demand on brain banks that collect and store valuable human post-mortem tissue. Our study aims to evaluate in lipidomics the potential of formalin-fixed tissue compared with the cryopreservation method, considered as the gold standard for biochemical research. Two complementary liquid chromatography/mass spectrometry analytical platforms were used on the basis of hybrid quadrupole time-of-flight and triple quadrupole mass spectrometers. Untargeted fingerprinting, semitargeted profiling of specific lipid classes and targeted monitoring of lipid species were performed in formalin-fixed and cryopreserved samples to provide detailed information at the molecular level on the formalin-induced alterations of the brain tissue. In vitro incubations of lipid standards were also performed to further describe the degradation processes induced by formaldehyde. Phospholipid compounds were found to be extensively hydrolysed, whilst the sphingolipid ones were preserved. N-methylation and N-formylation of amine-containing phospholipids have also been evidenced. These findings show that the potential detrimental effect of formalin on the analytes of interest must be taken into account when analysing formalin-fixed samples.

Published
2014

33. A single run LC-MS/MS method for phospholipidomics

Author

Jean-Marie Schmitter, Corinne Buré, Eric Testet, Sophie Ayciriex, Université Paris Descartes - Faculté de Pharmacie de Paris ( UPD5 Pharmacie ), Université Paris Descartes - Paris 5 ( UPD5 ), Max Planck Institute for Cell Biology and Genetics, Max-Planck-Institut, Institut des Sciences Analytiques ( ISA ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon, Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), UMR5200, Laboratoire de biogenèse membranaire (LBM), Université de Bordeaux ( UB ), Chimie et Biologie des Membranes et des Nanoobjets ( CBMN ), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux ( ENITAB ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), French Agence Nationale de la Recherche [NT09_517917], Region Aquitaine, platforms Proteome, Centre National de la Recherche Scientifique, Conseil Regional d'Aquitaine, Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS)

Subjects
ELECTROSPRAY-IONIZATION, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MECHANISTIC PROPOSAL, Tandem mass spectrometry, Phosphatidylinositols, 01 natural sciences, Biochemistry, ENERGY COLLISIONAL ACTIVATION, Analytical Chemistry, DATA-DEPENDENT ACQUISITION, chemistry.chemical_compound, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Tandem Mass Spectrometry, BIOLOGICAL SAMPLES, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Chromatography, High Pressure Liquid, Phospholipids, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Hydrophilic interaction chromatography, Phosphatidylglycerols, Phosphatidic acid, Phosphatidylserine, QUANTITATIVE-ANALYSIS, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Lipids, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, DRIVEN FRAGMENTATION PROCESSES, Phosphatidylcholines, Shotgun, Phospholipid, Liquid chromatography, Phosphatidic Acids, Phosphatidylserines, Chemistry Techniques, Analytical, 03 medical and health sciences, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Phosphatidylcholine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], TANDEM MASS-SPECTROMETRY, MULTIPLE PRECURSOR, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030304 developmental biology, Phosphatidylethanolamine, Chromatography, Mass spectrometry, Phosphatidylethanolamines, 010401 analytical chemistry, Fungi, Fatty acid, Reproducibility of Results, Carbon, 0104 chemical sciences, chemistry, SHOTGUN LIPIDOMICS, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry, Acyltransferases, Chromatography, Liquid, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

International audience; Liquid chromatography coupled to tandem mass spectrometry has been compared to shotgun analysis with the objective of finding the best compromise for a single run analysis of whole cell phospholipids. Hydrophilic interaction liquid chromatography (HILIC), normal phase (NP), and reversed phase (RP) liquid chromatography were evaluated with reference phospholipids belonging to phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), and phosphatidylserine (PS) classes. NP-HPLC- and RP-HPLC-ESI-MS/MS were applied to yeast phospholipidome analysis, using a wild-type strain and two strains defective for acyltransferases that are known to be involved in de novo phospholipid synthesis or phospholipid remodeling. The MRM mode was used for relative quantitation of individual compounds based on reference phospholipids bearing fatty acid chains with an odd number of carbon atoms. Combined LC-MS/MS was found superior to shotgun analysis, leading to a larger number of quantified species than shotgun analysis. Finally, RP-HPLC-MS/MS was the preferred method for its higher selectivity, robustness, and better repeatability.

Published
2013
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34. P2‐099: Lipidome of human microdissected senile plaques: Increased level of long‐chain saturated ceramides

Author

Maï Panchal, Olivier Laprévote, Nicolas Auzeil, Adina Lazar, Sophie Ayciriex, Charles Duyckaerts, Isabelle Rivals, and Mathieu Gaudin

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Biochemistry, Epidemiology, Chemistry, Health Policy, Neurology (clinical), Senile plaques, Geriatrics and Gerontology, Lipidome, Long chain
Published
2012
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35. Development of a novel method for quantification of sterols and oxysterols by UPLC-ESI-HRMS: application to a neuroinflammation rat model

Author

Sophie Ayciriex, Anne Regazzetti, Mathieu Gaudin, Elise Prost, Delphine Dargère, France Massicot, Nicolas Auzeil, and Olivier Laprévote

Subjects
Lipopolysaccharides, Analyte, Spectrometry, Mass, Electrospray Ionization, Electrospray ionization, Rat model, Mass spectrometry, Biochemistry, High-performance liquid chromatography, Sensitivity and Specificity, Analytical Chemistry, chemistry.chemical_compound, polycyclic compounds, Animals, Rats, Wistar, Derivatization, Mice brain, Neuroinflammation, Chromatography, High Pressure Liquid, Brain Chemistry, Inflammation, Chromatography, Brain, Rats, Sterols, chemistry, lipids (amino acids, peptides, and proteins), Carbamates
Abstract

Cholesterol and oxysterols are involved as key compounds in the development of severe neurodegenerative diseases and in neuroinflammation processes. Monitoring their concentration changes under pathological conditions is of interest to get insights into the role of lipids in diseases. For numerous years, liquid chromatography coupled to mass spectrometry has been the method of choice for metabolites identification and quantification in biological samples. However, sterols and oxysterols are relatively apolar molecules poorly adapted to electrospray ionization (ESI). To circumvent this drawback, we developed a novel and robust analytical method involving derivatization of these analytes in cholesteryl N-4-(N,N-dimethylamino)phenyl carbamates under alkaline conditions followed by ultra-performance liquid chromatography–high resolution mass spectrometry analysis (UPLC-HRMS). Optimized UPLC conditions led to the separation of a mixture of 11 derivatized sterols and oxysterols especially side chain substituted derivatives after 6 min of chromatographic run. High sensitivity time-of-flight mass analysis allowed analytes to be detected in the nanomolar range. The method was validated for the analysis of oxysterols and sterols in mice brain in respect of linearity, limits of quantification, accuracy, precision, analyte stability, and recovery according to the Food and Drug Administration (FDA) guidelines. The developed method was successfully applied to investigate the impact of lipopolysaccharide (LPS) treatment on the rat cerebral steroidome.

Published
2012

36. YPR139c/LOA1 encodes a novel lysophosphatidic acid acyltransferase associated with lipid droplets and involved in TAG homeostasis

Author

Sophie Ayciriex, Jean-William Dupuy, René Lessire, Jean-Marie Schmitter, Gisèle Velours, Mario Schoene, Sebastien Leone, Jean-Jacques Bessoule, Valérie Wattelet-Boyer, Andrej Shevchenko, Marina Le Guédard, Eric Testet, Nadine Camougrand, Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut de biochimie et génétique cellulaires (IBGC), LIMES Membrane Biology & Lipid Biochemistry, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2], Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, and Grellety, Marie-Lise

Subjects
Saccharomyces cerevisiae Proteins, Mutant, Saccharomyces cerevisiae, Biosynthesis and Biodegradation, Phospholipid, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Endoplasmic Reticulum, 03 medical and health sciences, chemistry.chemical_compound, Lipid droplet, Organelle, Homeostasis, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Triglycerides, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, Endoplasmic reticulum, 030302 biochemistry & molecular biology, Cell Biology, Articles, Lipidome, biology.organism_classification, Biochemistry, chemistry, Acyltransferase, Gene Knockdown Techniques, lipids (amino acids, peptides, and proteins), Acyltransferases
Abstract

LOA1, a yeast member of the glycerolipid acyltransferase family, encodes a novel lysophosphatidic acid acyltransferase associated with lipid droplets (LDs) and involved in triacylglycerol (TAG) accumulation. Loa1p, recruited during LD formation, preferentially directs oleic acid–containing phosphatidic acid species into the TAG biosynthetic pathway., For many years, lipid droplets (LDs) were considered to be an inert store of lipids. However, recent data showed that LDs are dynamic organelles playing an important role in storage and mobilization of neutral lipids. In this paper, we report the characterization of LOA1 (alias VPS66, alias YPR139c), a yeast member of the glycerolipid acyltransferase family. LOA1 mutants show abnormalities in LD morphology. As previously reported, cells lacking LOA1 contain more LDs. Conversely, we showed that overexpression results in fewer LDs. We then compared the lipidome of loa1Δ mutant and wild-type strains. Steady-state metabolic labeling of loa1Δ revealed a significant reduction in triacylglycerol content, while phospholipid (PL) composition remained unchanged. Interestingly, lipidomic analysis indicates that both PLs and glycerolipids are qualitatively affected by the mutation, suggesting that Loa1p is a lysophosphatidic acid acyltransferase (LPA AT) with a preference for oleoyl-CoA. This hypothesis was tested by in vitro assays using both membranes of Escherichia coli cells expressing LOA1 and purified proteins as enzyme sources. Our results from purification of subcellular compartments and proteomic studies show that Loa1p is associated with LD and active in this compartment. Loa1p is therefore a novel LPA AT and plays a role in LD formation.

Published
2012
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37. Time-of-flight secondary ion mass spectrometry: a novel tool for lipid imaging

Author

David Touboul, Olivier Laprévote, Sophie Ayciriex, Alain Brunelle, Institut de Chimie des Substances Naturelles (ICSN), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
MALDI imaging, 0303 health sciences, Materials science, Ion beam, business.industry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Endocrinology, Diabetes and Metabolism, 010401 analytical chemistry, Selected reaction monitoring, Top-down proteomics, Mass spectrometry, 01 natural sciences, Mass spectrometry imaging, 0104 chemical sciences, Secondary ion mass spectrometry, 03 medical and health sciences, Time of flight, Optics, Cardiology and Cardiovascular Medicine, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

Mass spectrometry imaging is becoming an important complementary alternative technique to more well-established imaging techniques. It can determine the spatial distribution of a large number of intact molecular or fragment ions generated directly from tissue sections or single cells. Secondary ion mass spectrometry coupled with a time-of-flight mass spectrometer imaging technique, using a cluster ion beam as primary bombardment particles, is now an analytical tool of reference for high lateral resolution imaging (1–2 µm) of biological surfaces. It exhibits a high efficiency for lipids and inorganic species. While numerous studies have been performed with cells in culture or with animal models, few clinical studies dedicated to lipid perturbations have been performed, to date. This article will compare the main advantages of time-of-flight mass spectrometry imaging over other mass spectrometry imaging methods and several biological applications will be detailed.

Published
2011
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38. PSI1 is responsible for the stearic acid enrichment that is characteristic of phosphatidylinositol in yeast

Author

Marina, Le Guédard, Jean-Jacques, Bessoule, Valérie, Boyer, Sophie, Ayciriex, Gisèle, Velours, Willem, Kulik, Christer S, Ejsing, Andrej, Shevchenko, Denis, Coulon, René, Lessire, Eric, Testet, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), and Grellety, Marie-Lise

Subjects
Saccharomyces cerevisiae Proteins, Microsomes, Saccharomyces cerevisiae, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Phosphatidylinositols, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Acyltransferases, Stearic Acids, ComputingMilieux_MISCELLANEOUS
Abstract

In yeast, both phosphatidylinositol and phosphatidylserine are synthesized from cytidine diphosphate-diacylglycerol. Because, as in other eukaryotes, phosphatidylinositol contains more saturated fatty acids than phosphatidylserine (and other phospholipids), it has been hypothesized that either phosphatidylinositol is synthesized from distinct cytidine diphosphate-diacylglycerol molecules, or that, after its synthesis, it is modified by a hypothetical acyltransferase that incorporates saturated fatty acid into neo-synthesized molecules of phosphatidylinositol. We used database search methods to identify an acyltransferase that could catalyze such an activity. Among the various proteins that we studied, we found that Psi1p (phosphatidylinositol stearoyl incorporating 1 protein) is required for the incorporation of stearate into phosphatidylinositol because GC and MS analyses of psi1Delta lipids revealed an almost complete disappearance of stearic (but not of palmitic acid) at the sn-1 position of this phospholipid. Moreover, it was found that, whereas glycerol 3-phosphate, lysophosphatidic acid and 1-acyl lysophosphatidylinositol acyltransferase activities were similar in microsomal membranes isolated from wild-type and psi1Delta cells, microsomal membranes isolated from psi1Delta cells are devoid of the sn-2-acyl-1-lysolysophosphatidylinositol acyltransferase activity that is present in microsomal membranes isolated from wild-type cells. Moreover, after the expression of PSI1 in transgenic psi1Delta cells, the sn-2-acyl-1-lysolysophosphatidylinositol acyltransferase activity was recovered, and was accompanied by a strong increase in the stearic acid content of lysophosphatidylinositol. As previously suggested for phosphatidylinositol from animal cells (which contains almost exclusively stearic acid as the saturated fatty acid), the results obtained in the present study demonstrate that the existence of phosphatidylinositol species containing stearic acid in yeast results from a remodeling of neo-synthesized molecules of phosphatidylinositol.

Published
2009

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