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1. CD36 gene polymorphism is associated with Alzheimer's disease

Author

Vladimir J. Balcar, Alice Hálová, Vladimir Janout, Laura Ewerlingová, Jan Lochman, Jana Janoutová, Naim Akhtar Khan, Omar Šerý, Department of biochemistry, Masaryk University, Masaryk University [Brno] (MUNI), Institute of Animal Physiology and Genetics (Brno), Institute of Animal Physiology and Genetics, Department of Epidemiology and Public Health [university of Ostrava], Lékařská fakulta / Faculty of Medicine [University of Ostrava], Ostravská univerzita / University of Ostrava-Ostravská univerzita / University of Ostrava, Equipe NuTox (LNC - U1231) (NUTOX), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Bosch Institute [Sydney], The University of Sydney, Discipline of Anatomy and Histology {University of Sydney], Masaryk University, Equipe NuTox (LNC - U1231) ( NUTOX ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and The University of Sydney [Sydney]

Subjects
0301 basic medicine, Apolipoprotein E, MESH : Oxidative Stress, CD36 Antigens, Male, MESH : Polymorphism, Genetic, CD36, MESH : Aged, MESH : Alzheimer Disease, MESH : Genotype, Biochemistry, Gene, MESH: Genotype, 0302 clinical medicine, MESH: Cholesterol, MESH : Female, MESH : Cholesterol, Genetics, MESH: Aged, MESH: Oxidative Stress, biology, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, General Medicine, 3. Good health, MESH : Antigens, CD36, Cholesterol, Interleukin 18, Female, ApoE, Genotype, MESH : Male, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, MMSE, Association, 03 medical and health sciences, Alzheimer Disease, MESH: Polymorphism, Genetic, SNP, Humans, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Allele, Polymorphism, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetic association, Aged, Polymorphism, Genetic, MESH: Humans, MESH: Antigens, CD36, MESH : Humans, MESH: Male, Oxidative Stress, 030104 developmental biology, biology.protein, MESH : Genetic Predisposition to Disease, Gene polymorphism, MESH: Female, 030217 neurology & neurosurgery, MESH: Alzheimer Disease
Abstract

IF 3.112; International audience; CD36 gene encodes a membrane glycoprotein (type B scavenger receptor) present on the surface of many types of cells and having multiple cellular functions ranging from angiogenesis to gustatory perception of fatty acids. Using a case control genetic association approach we have analyzed selected single nucleotide polymorphisms (SNP's) in a total of 859 patients with Alzheimer's disease (AD) and controls and have identified the allele A in rs3211892 polymorphism of CD36 gene as significantly increasing the risk of AD. Additionally we have investigated, in the same sample of control subjects and patients, SNP's in ApoE gene and confirmed that the previously identified AD-associated SNP's indeed increased the risk and decreased the age of onset of AD as reported by others earlier. Based on the current knowledge of CD36 biochemistry we propose that the AD risk-imparting variants of CD36 alter cholesterol homeostasis, oxidation stress or induce pathological inflammatory cascades. The SNP rs3211892 has previously been associated with heart disease and other conditions but the present study is the first to identify a significant association between variations in CD36 gene and the risk of Alzheimer's disease.

Published
2017
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2. Shifted, the Drosophila Ortholog of Wnt Inhibitory Factor-1, Controls the Distribution and Movement of Hedgehog

Author

Michael A. Halbisen, Bruno Glise, Alain Vincent, Michèle Crozatier, Steve Wise, Catherine A. Miller, David J. Olson, Seth S. Blair, Institut de Recherches et d'Etudes sur le Monde Arabe et Musulman (IREMAM), Sciences Po Aix - Institut d'études politiques d'Aix-en-Provence (IEP Aix-en-Provence)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Bordelais de Recherche en Informatique (LaBRI), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Anatomopathologie Haut-Lévêque (ANATOMOPATHOLOGIE), CHU, Clinical Neurology Oxford (CLINICAL NEUROLOGY), Hospital, Departement /u661 : Endocrinologie, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de synthèse organique (DCSO), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), FLAveur, VIsion et Comportement du consommateur (FLAVIC), Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Institut de Recherches et d'Etudes sur les Mondes Arabes et Musulmans (IREMAM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), École polytechnique (X)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches et d'Etudes sur le Monde Arabe et Musulman ( IREMAM ), Sciences Po Aix - Institut d'études politiques d'Aix-en-Provence ( IEP Aix-en-Provence ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biologie du développement ( CBD ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Bordelais de Recherche en Informatique ( LaBRI ), Centre National de la Recherche Scientifique ( CNRS ) -École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Anatomopathologie Haut-Lévêque ( ANATOMOPATHOLOGIE ), Clinical Neurology Oxford ( CLINICAL NEUROLOGY ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de synthèse organique ( DCSO ), École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), FLAveur, VIsion et Comportement du consommateur ( FLAVIC ), Etablissement National d'Enseignement Supérieur Agronomique de Dijon ( ENESAD ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Recherche Agronomique (INRA)-Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Université de Bourgogne (UB)

Subjects
Male, MESH: Signal Transduction, MESH : Molecular Sequence Data, MESH: Sequence Homology, Amino Acid, MESH: Drosophila, MESH : Animals, Genetically Modified, Sequence Homology, MESH : Models, Biological, MESH: Amino Acid Sequence, Wing, MESH: Cholesterol, 0302 clinical medicine, Models, Drosophila Proteins, MESH : Female, MESH: Animals, MESH : Cholesterol, Genetics, 0303 health sciences, biology, MESH : Amino Acid Sequence, Wnt signaling pathway, Signal transducing adaptor protein, MESH : Sequence Homology, Amino Acid, Hedgehog signaling pathway, Cell biology, MESH : Phenotype, Amino Acid, Imaginal disc, Cholesterol, Phenotype, MESH: Repressor Proteins, Drosophila, Female, MESH : Mutation, MESH : Repressor Proteins, MESH : Carrier Proteins, Drosophila melanogaster, Signal transduction, MESH : Heparan Sulfate Proteoglycans, Drosophila Protein, Signal Transduction, MESH: Mutation, animal structures, MESH: Drosophila Proteins, MESH : Male, Molecular Sequence Data, MESH : Wing, Genetically Modified, MESH: Carrier Proteins, MESH: Phenotype, General Biochemistry, Genetics and Molecular Biology, MESH: Animals, Genetically Modified, 03 medical and health sciences, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, MESH : Drosophila, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Hedgehog, Alleles, 030304 developmental biology, MESH : Signal Transduction, MESH: Humans, MESH: Molecular Sequence Data, MESH: Alleles, MESH : Humans, MESH: Models, Biological, Cell Biology, MESH : Drosophila Proteins, Biological, MESH: Wing, biology.organism_classification, MESH: Male, Repressor Proteins, Mutation, MESH: Heparan Sulfate Proteoglycans, MESH : Animals, MESH : Alleles, Carrier Proteins, MESH: Female, Heparan Sulfate Proteoglycans, 030217 neurology & neurosurgery, Developmental Biology
Abstract

SummaryWe here identify and characterize an extracellular modulator of Hedgehog signaling in Drosophila, Shifted. Shifted is required for high levels of long-range signaling in the developing wing imaginal disc. Surprisingly, shifted encodes the only Drosophila ortholog of the secreted vertebrate protein Wnt Inhibitory Factor-1 (WIF-1), whose known role is to bind to extracellular Wnts and inhibit their activity. However, Shifted does not regulate Hedgehog signaling by affecting Wingless or Wnt signaling. We show instead that Shifted is a secreted protein that acts over a long distance and is required for the normal accumulation of Hh protein and its movement in the wing. Our data further indicate that Shf interacts with Hh and the heparan sulfate proteoglycans. Therefore, we propose that Shf stabilizes the interaction between Hh and the proteoglycans, an unexpected role for a member of the WIF-1 family.

Published
2005
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3. Single nucleotide polymorphism in the cholesterol-24S-hydroxylase (CYP46A1) gene and its association with CFH and LOC387715 gene polymorphisms in age-related macular degeneration

Author

Brice Dugas, Jennyfer Zerbib, Ingemar Björkhem, Niyazi Acar, Nathalie Puche, Catherine Creuzot-Garcher, Nicolas Leveziel, J.-F. Korobelnik, Cynthia Fourgeux, Lionel Bretillon, Florence Richard, Alain M. Bron, Eric H Souied, Centre des Sciences du Goût et de l'Alimentation (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Epidémiologie des maladies chroniques: impact des intéractions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Service d'ophtalmologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Programme Hospitalier de Recherche Clinique (Direction de la Recherche Clinique de l'Hôpital universitaire (Dijon, France) and Fournier/Solvay/Abbott Laboratory (Daix, France)., Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), and Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 )

Subjects
Male, Genotyping Techniques, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MESH : Aged, MESH : Gas Chromatography-Mass Spectrometry, Gastroenterology, MESH : Proteins, MESH : Hydroxycholesterols, MESH: Hydroxycholesterols, 0302 clinical medicine, MESH: Cholesterol, Risk Factors, MESH: Risk Factors, Genotype, Odds Ratio, MESH : Female, MESH: Proteins, MESH : Geographic Atrophy, MESH : Cholesterol, Genetics, MESH: Aged, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, MESH : Genotyping Techniques, MESH : Risk Factors, 3. Good health, Cholesterol, MESH: Complement Factor H, Complement Factor H, Female, MESH: Steroid Hydroxylases, medicine.medical_specialty, MESH : Male, Single-nucleotide polymorphism, MESH : Wet Macular Degeneration, Biology, Polymorphism, Single Nucleotide, Gas Chromatography-Mass Spectrometry, 03 medical and health sciences, Internal medicine, Geographic Atrophy, MESH: Genotyping Techniques, medicine, Cholesterol 24-Hydroxylase, SNP, Humans, Allele, Gene, Alleles, Aged, MESH: Geographic Atrophy, MESH : Steroid Hydroxylases, MESH: Humans, MESH: Alleles, MESH : Humans, Proteins, Odds ratio, Macular degeneration, medicine.disease, Confidence interval, Hydroxycholesterols, eye diseases, MESH: Male, MESH: Odds Ratio, MESH: Gas Chromatography-Mass Spectrometry, MESH : Complement Factor H, Steroid Hydroxylases, 030221 ophthalmology & optometry, Wet Macular Degeneration, MESH : Odds Ratio, MESH: Wet Macular Degeneration, sense organs, MESH : Alleles, MESH: Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery
Abstract

International audience; PURPOSE: We investigated the association of single nucleotide polymorphism (SNP) in the cholesterol-24S-hydroxylase (CYP46A1) gene, according to CFH and LOC387715 SNPs, with age-related macular degeneration (AMD). METHODS: We enrolled 1388 AMD patients with neovascular AMD or geographic atrophy and 487 unrelated control subjects. SNPs were genotyped in the CYP46A1 (rs754203), LOC387715 (rs10490924), and CFH (rs1061170) genes. Plasma 24S-hydroxycholesterol, the metabolic product of CYP46A1, was quantified by gas chromatography-mass spectrometry using an authentic deuterated internal standard in subgroups of patients and controls. The χ(2) test was used to compare categoric allelic and genotype distributions between cases and controls. The odds ratio (OR) with a 95% confidence interval (95% CI) was calculated for AMD risk, and adjusted for age and gender. Significance levels were set at P < 0.05. RESULTS: The rs754203 SNP in the CYP46A1 gene was not associated with AMD (crude OR = 1.2, 95% CI = 0.9-1.4, P = 0.2). The crude OR for risk of AMD was 2.9 (95% CI = 2.4-3.4, P < 0.0001) according to the number of rs10490924 T alleles in the LOC387715 gene, and 2.0 (95% CI = 1.7-2.3, P < 0.0001) according to the number of rs1061170 C alleles in the CFH gene. After adjustment for age and gender, an OR of 2.2 (95% CI = 1.1-4.1, P = 0.04) was obtained for AMD cases with the C allele in the CYP46A1 gene, and carrying no risk alleles in the CFH and LOC387715 genes. CONCLUSIONS: The rs754203 C allele in the CYP46A1 gene may confer a higher risk for exudative AMD in patients who carry no risk alleles in the CFH and LOC387715 genes. Additional studies with larger sample sizes are needed in AMD subjects at no risk in CFH and LOC387715.

Published
2012
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4. A role for the peroxisomal 3-ketoacyl-CoA thiolase B enzyme in the control of PPARα-mediated upregulation of SREBP-2 target genes in the liver.: ThB and cholesterol biosynthesis in the liver

Author

Marc Espeel, Norbert Latruffe, Marie Charlotte Royer, Grégory Chevillard, Ronald J.A. Wanders, Melina De Bruycker, Valérie Nicolas-Francès, Sander Kersten, Ségolène Arnauld, Anne Athias, Pierre Clouet, Marie Claude Clémencet, Stéphane Mandard, Joseph Gresti, Pascal Degrace, Marco Fidaleo, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Department of Human Anatomy, Embryology, Histology and Medical Physics, Universiteit Gent = Ghent University [Belgium] (UGENT), Laboratory Genetic Metabolic Diseases, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Universiteit van Amsterdam (UvA), Plateforme Lipidomique [Dijon] (LAP), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Nutrition, Metabolism and Genomics Group, Wageningen University and Research [Wageningen] (WUR), This work was supported by grants from the European Union project 'Peroxisomes' LSHG-CT-2004-512018, the Regional Council of Burgundy and the INSERM U866 center (Dijon). G.C. was supported by a French Ministry of Research and Technology Ph.D. fellowship and M.F. by the Italian 'Ministero della Ricerca Scientifica e Tecnologica'., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Ghent University [Belgium] ( UGENT ), Universiteit van Amsterdam ( UvA ) -Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), Plateforme Lipidomique [Dijon] ( LAP ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Wageningen University and Research Centre [Wageningen] ( WUR ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Universiteit van Amsterdam (UvA)-Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)

Subjects
Male, MESH: Hepatomegaly, Palmitates, MESH : Pyrimidines, MESH : Gene Deletion, Biochemistry, element-binding proteins, MESH : Acetyl-CoA C-Acyltransferase, Mice, MESH: Up-Regulation, MESH: Animals, MESH : Up-Regulation, MESH: Lipid Metabolism, 0303 health sciences, MESH : Gene Expression Regulation, Thiolase, 030302 biochemistry & molecular biology, General Medicine, MESH : Hepatomegaly, Up-Regulation, zellweger-syndrome, Peroxisome Proliferators, MESH: Peroxisome Proliferators, Hepatomegaly, Sterol Regulatory Element Binding Protein 2, peroxisomal 3-ketoacyl-CoA thiolase B, MESH: Mitochondria, 3-oxoacyl-coa thiolase, Lathosterol, fatty-acid oxidation, rat-liver, MESH: Sterol Regulatory Element Binding Protein 2, 03 medical and health sciences, MESH : Sterol Regulatory Element Binding Protein 2, Humans, PPAR alpha, MESH : Peroxisome Proliferators, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, PPARa, VLAG, MESH : Oxidation-Reduction, Fatty Acid Oxidation, MESH: Humans, Cholesterol, MESH : Humans, cholesterol, Lipid Metabolism, MESH: Peroxisomes, Sterol regulatory element-binding protein, chemistry, MESH: Pyrimidines, Micro-array analysis, Peroxisomal 3-ketoacyl-CoA thiolase B, PPARα and SREBP-2, Wy14,643, Gene Deletion, MESH: Liver, MESH: Oxidation-Reduction, MESH: Signal Transduction, MESH: Mice, Knockout, Voeding, Metabolisme en Genomica, chemistry.chemical_compound, MESH: Cholesterol, MESH : Lipid Metabolism, Wy14, MESH : Palmitates, MESH: PPAR alpha, MESH : Cholesterol, Mice, Knockout, neuronal migration, Peroxisome, Acetyl-CoA C-Acyltransferase, MESH: Gene Expression Regulation, Metabolism and Genomics, Mitochondria, Liver, Metabolisme en Genomica, ACOX1, Nutrition, Metabolism and Genomics, MESH : Mitochondria, Oxidation-Reduction, Signal Transduction, acyl-coa oxidase, cholesterol-synthesis, MESH : Male, MESH : PPAR alpha, Peroxisome Proliferation, Biology, beta-oxidation, Voeding, proliferator-activated receptors, MESH : Mice, Peroxisomes, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, SCP2, Nutrition, MESH : Signal Transduction, MESH : Liver, MESH: Palmitates, MESH: Male, Pyrimidines, MESH: Acetyl-CoA C-Acyltransferase, Gene Expression Regulation, MESH: Gene Deletion, MESH : Mice, Knockout, MESH : Animals, MESH : Peroxisomes
Abstract

International audience; Peroxisomal 3-ketoacyl-CoA thiolase B (Thb) catalyzes the final step in the peroxisomal β-oxidation of straight-chain acyl-CoAs and is under the transcription control of the nuclear hormone receptor PPARα. PPARα binds to and is activated by the synthetic compound Wy14,643 (Wy). Here, we show that the magnitude of Wy-mediated induction of peroxisomal β-oxidation of radiolabeled (1-(14)C) palmitate was significantly reduced in mice deficient for Thb. In contrast, mitochondrial β-oxidation was unaltered in Thb(-/-) mice. Given that Wy-treatment induced Acox1 and MFP-1/-2 activity at a similar level in both genotypes, we concluded that the thiolase step alone was responsible for the reduced peroxisomal β-oxidation of fatty acids. Electron microscopic analysis and cytochemical localization of catalase indicated that peroxisome proliferation in the liver after Wy-treatment was normal in Thb(-/-) mice. Intriguingly, micro-array analysis revealed that mRNA levels of genes encoding cholesterol biosynthesis enzymes were upregulated by Wy in Wild-Type (WT) mice but not in Thb(-/-) mice, which was confirmed at the protein level for the selected genes. The non-induction of genes encoding cholesterol biosynthesis enzymes by Wy in Thb(-/-) mice appeared to be unrelated to defective SREBP-2 or PPARα signaling. No difference was observed in the plasma lathosterol/cholesterol ratio (a marker for de novo cholesterol biosynthesis) between Wy-treated WT and Thb(-/-) mice, suggesting functional compensation. Overall, we conclude that ThA and SCPx/SCP2 thiolases cannot fully compensate for the absence of ThB. In addition, our data indicate that ThB is involved in the regulation of genes encoding cholesterol biosynthesis enzymes in the liver, suggesting that the peroxisome could be a promising candidate for the correction of cholesterol imbalance in dyslipidemia.

Published
2011
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5. Effects of oxysterols on cell viability, inflammatory cytokines, VEGF, and reactive oxygen species production on human retinal cells: cytoprotective effects and prevention of VEGF secretion by resveratrol

Author

Franck Ménétrier, Am Bron, Catherine Creuzot-Garcher, T. Khalfaoui, Jeannine Lherminier, L. Malvitte, Dominique Delmas, Kévin Ragot, Soeli Charbonnier, Norbert Latruffe, Mauhamad Baarine, Brice Dugas, Gérard Lizard, Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), FLAveur, VIsion et Comportement du consommateur ( FLAVIC ), Etablissement National d'Enseignement Supérieur Agronomique de Dijon ( ENESAD ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ), Agroécologie [Dijon], Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, This work was supported by grants from the INSERM, and the University Hospital of Dijon (CHU de Dijon)., Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), FLAveur, VIsion et Comportement du consommateur (FLAVIC), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), and Latruffe, Norbert

Subjects
MESH: Cell Death, MESH: Inflammation, Vascular Endothelial Growth Factor A, MESH : Cell Line, inflammatory cytokines, medicine.medical_treatment, MESH : Cytokines, Medicine (miscellaneous), MESH : Reactive Oxygen Species, Wine, Resveratrol, Pharmacology, resveratrol, MESH : Cytoprotection, Antioxidants, chemistry.chemical_compound, 0302 clinical medicine, MESH: Cholesterol, MESH: Stilbenes, Stilbenes, polycyclic compounds, [ SHS.INFO ] Humanities and Social Sciences/Library and information sciences, MESH : Cholesterol, Phospholipids, chemistry.chemical_classification, reactive oxygen species, 0303 health sciences, MESH: Cytokines, MESH : Cell Survival, Nutrition and Dietetics, Cell Death, MESH: Retina, food and beverages, MESH: Reactive Oxygen Species, phospholipidosis, Cytoprotection, VEGF, 3. Good health, Cytokine, Cholesterol, MESH: Cell Survival, MESH : Vascular Endothelial Growth Factor A, Cytokines, oxysterols, MESH : Antioxidants, lipids (amino acids, peptides, and proteins), medicine.symptom, Programmed cell death, Cell Survival, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, MESH : Wine, Inflammation, Biology, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, Retina, MESH : Phospholipids, Proinflammatory cytokine, Cell Line, MESH : Stilbenes, 03 medical and health sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Viability assay, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Phospholipids, Reactive oxygen species, MESH: Humans, MESH : Inflammation, MESH: Vascular Endothelial Growth Factor A, MESH: Antioxidants, MESH : Humans, MESH : Retina, MESH: Wine, MESH: Cell Line, MESH: Cytoprotection, chemistry, MESH : Cell Death, Immunology, 030221 ophthalmology & optometry, caspase independent cell death, ARPE-19 cells
Abstract

Oxysterols are assumed to play important roles in age-related macular degeneration, a major cause of blindness. So we characterized the cytotoxic, oxidative, inflammatory, and angiogenic activities of oxysterols (7β-hydroxycholesterol (7β-OH), 7-ketocholesterol (7KC), 25-hydroxycholesterol (25-OH)) in human retinal ARPE-19 cells, and evaluated the protective effects of resveratrol (Rsv: 1 μM), a polyphenol from red wine.ARPE-19 cells were treated with 7β-OH, 7KC, or 25-OH (5-40 μg/mL; 24-48 h) without or with Rsv. Cell viability was determined using trypan blue and the MTT assay. Cell death was characterized by electron microscopy and in situ detection of activated caspases with fluorochrome-labeled inhibitors of caspases. Reactive oxygen species (ROS) production was measured with hydroethidine. ELISA methods and a cytometric bead assay were used to quantify cytokines involved in inflammation (IL-8, IL-1β, IL-6, IL-10, IL-12p70, TNF-α, MCP-1) and VEGF.7β-OH and 7KC triggered a caspase-independent cell death process associated with the presence of multilamellar cytoplasmic structures evocating phospholipidosis, increased ROS production, and IL-8 secretion. 7β-OH enhanced VEGF secretion. No cytotoxic effects were identified with 25-OH, which highly stimulated ROS production, MCP-1, and VEGF secretion. With oxysterols, no IL-10, TNF-α, and IL-12p70 secretion were detected. 25-OH induced IL-8 secretion through the MEK/ERK½ signaling pathway, and Rsv showed cytoprotective activities and inhibited VEGF secretion.7β-OH, 7KC, and 25-OH have cytotoxic, oxidative, inflammatory, and/or angiogenic activities on ARPE-19 cells. As Rsv has some protective effects against oxysterol-induced cell death and VEGF secretion it could be valuable in ARMD treatment.

Published
2010
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6. Vitamin E transport in enterocytes

Author

Béatrice Gleize, Xavier Collet, Martina Schneider, Emmanuelle Reboul, Alexis Klein, Alain Margotat, Patrick Borel, Christiane Malezet-Desmoulins, Laurent Lagrost, Florence Bietrix, Nutrition humaine et lipides : Biodisponibilité, métabolisme et régulation, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique ( INRA ) -Université de Provence - Aix-Marseille 1-IFR125-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire des Lipoprotéines humaines et interactions vasculaires, Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Physiopathologie Toulouse Purpan, and Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
CD36 Antigens, Lutein, Time Factors, 030309 nutrition & dietetics, medicine.medical_treatment, alpha-Tocopherol, Tocopherols, MESH : Dose-Response Relationship, Drug, Biochemistry, Intestinal absorption, chemistry.chemical_compound, Mice, Vitamin E, Intestinal Mucosa, MESH : Cholesterol, Micelles, MESH : Intestines, 0303 health sciences, Temperature, Cell Differentiation, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Intestinal epithelium, Lipids, MESH : Mice, Transgenic, MESH : Epithelial Cells, MESH : Enterocytes, MESH : Antigens, CD36, medicine.anatomical_structure, Cholesterol, MESH : Cell Differentiation, medicine.medical_specialty, Enterocyte, Mice, Transgenic, Biology, Binding, Competitive, Article, Absorption, 03 medical and health sciences, Internal medicine, MESH : Mice, MESH : Micelles, medicine, Animals, Humans, RNA, Messenger, Scavenger receptor, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, gamma-Tocopherol, Dose-Response Relationship, Drug, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH : Binding, Competitive, MESH : Humans, MESH : Caco-2 Cells, MESH : Lipids, Biological Transport, Epithelial Cells, Cell Biology, Bioavailability, MESH : Absorption, MESH : Biological Transport, Endocrinology, Enterocytes, chemistry, MESH : Animals, Caco-2 Cells
Abstract

Although cellular uptake of vitamin E was initially described as a passive process, recent studies in the liver and brain have shown that SR-BI (scavenger receptor class B type I) is involved in this phenomenon. As SR-BI is expressed at high levels in the intestine, the present study addressed the involvement of SR-BI in vitamin E trafficking across enterocytes. Apical uptake and efflux of the main dietary forms of vitamin E were examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium. (R,R,R)-gamma-tocopherol bioavailability was compared between wild-type mice and mice overexpressing SR-BI in the intestine. The effect of vitamin E on enterocyte SR-BI mRNA levels was measured by real-time quantitative reverse transcription-PCR. Concentration-dependent curves for vitamin E uptake were similar for (R,R,R)-alpha-, (R,R,R)-gamma-, and dl-alpha-tocopherol. (R,R,R)-alpha-tocopherol transport was dependent on incubation temperature, with a 60% reduction in absorption at 4 degrees C compared with 37 degrees C (p < 0.05). Vitamin E flux in enterocytes was directed from the apical to the basal side, with a relative 10-fold reduction in the transfer process when measured in the opposite direction (p < 0.05). Co-incubation with cholesterol, gamma-tocopherol, or lutein significantly impaired alpha-tocopherol absorption. Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 80% of vitamin E uptake and up to 30% of apical vitamin E efflux (p < 0.05), and similar results were obtained for (R,R,R)-gamma-tocopherol. SR-BI mRNA levels were not significantly modified after a 24-h incubation of Caco-2 cells with vitamin E. Finally, (R,R,R)-gamma-tocopherol bioavailability was 2.7-fold higher in mice overexpressing SR-BI than in wild-type mice (p < 0.05). The present data show for the first time that vitamin E intestinal absorption is, at least in part, mediated by SR-BI.

Published
2005
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7. 7-Ketocholesterol favors lipid accumulation and colocalizes with Nile Red positive cytoplasmic structures formed during 7-ketocholesterol-induced apoptosis: analysis by flow cytometry, FRET biphoton spectral imaging microscopy, and subcellular fractionation

Author

Ginette Bessède, Gérard Lizard, Edmond Kahn, Anne Vejux, Jean-Marc Riedinger, Andrew Todd-Pokropek, Anne Athias, Franck Ménétrier, Frédérique Frouin, Eric Ogier-Denis, Jean-François Stoltz, Dominique Dumas, Laboratoire de Biochimie Moléculaire et Cellulaire ( LBMC ), Université de Bourgogne ( UB ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Laboratoire d'Imagerie Fonctionnelle ( LIF ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Energétique et de Mécanique Théorique Appliquée ( LEMTA ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Plate-forme Imagerie et Biophysique Cellulaire et Tissulaire ( PTIBC-IBISA Nancy ), Université Henri Poincaré - Nancy 1 ( UHP ), Plateforme Lipidomique [Dijon] ( LAP ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Laboratoire de Biologie Médicale [Centre Georges-François leclerc], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Faculté de Médecine Xavier Bichat, Laboratoire de Biochimie Moléculaire et Cellulaire (LBMC), Université de Bourgogne (UB), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Plate-forme Imagerie et Biophysique Cellulaire et Tissulaire (PTIBC-IBISA Nancy), Université Henri Poincaré - Nancy 1 (UHP), Plateforme Lipidomique [Dijon] (LAP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)

Subjects
MESH: Flow Cytometry, Apoptosis, 7. Clean energy, law.invention, MESH : Phosphatidylcholines, 0302 clinical medicine, Fluorescence Resonance Energy Transfer, MESH : Fluorescent Dyes, Enzyme Inhibitors, MESH: Lipid Metabolism, 0303 health sciences, MESH : Cell Nucleus, Flow Cytometry, MESH: Image Processing, Computer-Assisted, Cholesterol, MESH : Propidium, 030220 oncology & carcinogenesis, MESH : U937 Cells, MESH: Microscopy, Electron, Transmission, MESH: Cell Fractionation, MESH : Image Processing, Computer-Assisted, MESH: Propidium, Propidium, MESH: Cell Nucleus, MESH : Sphingomyelins, MESH: Mitochondria, Cell Fractionation, Filipin, Permeability, Pathology and Forensic Medicine, 03 medical and health sciences, Microscopy, Electron, Transmission, Oxazines, MESH: Membrane Potentials, Humans, Propidium iodide, MESH: Humans, MESH : Oxazines, MESH : Humans, Nile red, MESH: Phosphatidylcholines, Lipid Metabolism, Förster resonance energy transfer, chemistry, MESH: Subcellular Fractions, Cytoplasmic Structures, Benzimidazoles, MESH : Apoptosis, MESH: Fluorescence Resonance Energy Transfer, MESH: Sphingomyelins, Membrane Potentials, chemistry.chemical_compound, MESH: Cholesterol, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], law, MESH : Lipid Metabolism, Image Processing, Computer-Assisted, Fluorescence microscope, MESH : Membrane Potentials, Ketocholesterols, MESH : Cholesterol, MESH: Ketocholesterols, U937 Cells, MESH: Fluorescent Dyes, Mitochondria, Sphingomyelins, MESH: Intracellular Membranes, MESH : Microscopy, Electron, Transmission, Biochemistry, MESH : Benzimidazoles, MESH: Enzyme Inhibitors, MESH: Permeability, MESH : Cell Fractionation, Phosphatidylcholines, lipids (amino acids, peptides, and proteins), MESH : Mitochondria, Cell fractionation, Subcellular Fractions, Histology, MESH : Flow Cytometry, MESH: U937 Cells, MESH : Subcellular Fractions, Confocal microscopy, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Fluorescent Dyes, 030304 developmental biology, MESH : Ketocholesterols, Cell Nucleus, MESH : Enzyme Inhibitors, MESH: Apoptosis, Lipid metabolism, Intracellular Membranes, Cell Biology, MESH : Cytoplasmic Structures, MESH: Cytoplasmic Structures, MESH : Intracellular Membranes, MESH : Permeability, MESH : Fluorescence Resonance Energy Transfer, MESH: Benzimidazoles, MESH: Oxazines
Abstract

Background Oxidized low-density lipoproteins play key roles in atherosclerosis. Their toxicity is at least in part due to 7-ketocholesterol (7KC), which is a potent inducer of apoptosis. In this study on human promonocytic U937 cells, we determined the effects and the interactions of 7KC with cellular lipids during 7KC-induced apoptosis. Methods Morphologic and functional changes were investigated by microscopic and flow cytometric methods after staining with propidium iodide, 3,3′-dihexyloxacarbocyanine iodide, and Hoechst 33342. Cellular lipid content was identified by using filipin to quantify free cholesterol and Nile Red (NR), which emit a yellow or orange-red fluorescence in the presence of neutral and polar lipids, respectively. After staining with NR, interactions of 7KC with cellular lipids were identified by fluorescence resonance energy transfer biphoton spectral imaging confocal microscopy and by subcellular fractionation, gas chromatography, and mass spectrometry. Results During 7KC-induced apoptosis the fluorescence from filipin and the ratio of measured (orange-red vs. yellow) fluorescence of NR were enhanced. Spectral analysis of images obtained in biphoton mode and resulting factor images demonstrated the occurrence of fluorescence resonance energy transfer between 7KC and NR and the subsequent colocalization of 7KC and NR. These data were in agreement with biochemical characterization and demonstrated that 7KC and neutral and polar lipids accumulate in NR-stained cytoplasmic structures. Conclusions During 7KC-induced apoptosis, 7KC modifies the cellular content of neutral and polar lipids, favors free cholesterol accumulation, and colocalizes with neutral and polar lipids that are inside NR-stained cytoplasmic structures. © 2005 Wiley-Liss, Inc.

Published
2005
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8. Shape modification of phospholipid vesicles induced by high pressure: influence of bilayer compressibility

Author

Jean-Marie Perrier-Cornet, Murielle Hayert, Laurent Beney, Patrick Gervais, Procédés Alimentaires et Microbiologiques ( PAM ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Génie industriel alimentaire ( GENIAL ), and Institut National de la Recherche Agronomique ( INRA ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Institut National Agronomique Paris-Grignon ( INA P-G ) -Ecole Nationale Supérieure des Industries Agricoles et alimentaires

Subjects
MESH : Microscopy, Phase-Contrast, Surface Properties, Hydrostatic pressure, Lipid Bilayers, Molecular Conformation, Biophysics, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH : Phosphatidylcholines, chemistry.chemical_compound, [ PHYS.PHYS.PHYS-BIO-PH ] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Phosphatidylcholine, Hydrostatic Pressure, Microscopy, Phase-Contrast, MESH : Surface Properties, Water content, MESH : Cholesterol, Bilayer, Vesicle, [ SPI.GPROC ] Engineering Sciences [physics]/Chemical and Process Engineering, Compression (physics), MESH : Hydrostatic Pressure, Crystallography, Cholesterol, chemistry, Volume (thermodynamics), MESH : Molecular Conformation, Compressibility, Phosphatidylcholines, MESH : Lipid Bilayers, Research Article
Abstract

International audience; Giant vesicles composed of pure egg yolk phosphatidylcholine (EYPC) or containing cholesterol (28 mol%) have been studied during a high hydrostatic pressure treatment to 285 MPa by microscopic observation. During pressure loading the vesicles remain spherical. A shape transition consisting of budding only occurs on the cholesterol-free vesicles during pressure release. The decrease in the volume delimited by the pure EYPC bilayer between 0.1 and 285 MPa was found to be 16% of its initial volume, whereas the bulk compression of water in this pressure range is only 10%. So the compression at 285 MPa induced a water exit from the pure EYPC vesicle. The shape transition of the EYPC vesicle during pressure release is attributed to an increase in its area-to-volume ratio caused by the loss of its water content during compression. Because bulk compression of the cholesterol-containing vesicle is close to that of water, no water transfer would be induced across the bilayer and the vesicle remains spherical during the pressure release.

Published
1997
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