المؤلفون: Ursula Felderhoff-Müser, Wiebke Hansen, Ivo Bendix, Josephine Herz, Marco Sifringer, Katharina Lumpe, Karina Kempe, Ralf Herrmann, Martin Hadamitzky, Xinlin Hou, Yohan van de Looij, Meray Serdar, Stéphane Sizonenko, Barbara S. Reinboth, Rolf Heumann

المصدر: Brain, behavior, and immunity, Vol. 52 (2016) pp. 106-19

مصطلحات موضوعية: 0301 basic medicine, Male, Medizin, Sphingosine/analogs & derivatives/metabolism, medicine.disease_cause, Nerve Fibers, Myelinated, Cognition Disorders/metabolism/pathology/prevention & control, Behavioral Neuroscience, Microglia/drug effects/metabolism/pathology, Random Allocation, 0302 clinical medicine, Sphingosine, Pregnancy, hemic and lymphatic diseases, CIBM-AIT, Hyperoxia, ddc:618, Nerve Fibers, Myelinated/drug effects, Microglia, Brain, White Matter, Fingolimod, Oligodendroglia, Receptors, Lysosphingolipid, medicine.anatomical_structure, Female, medicine.symptom, medicine.drug, Oligodendroglia/drug effects/metabolism/pathology, Immunology, Biology, Neuroprotection, White matter, 03 medical and health sciences, Oxygen/administration & dosage, medicine, Animals, Brain/metabolism, Rats, Wistar, Fingolimod Hydrochloride/therapeutic use, White Matter/drug effects/metabolism/pathology, Fingolimod Hydrochloride, Endocrine and Autonomic Systems, Multiple sclerosis, Lysophospholipids/metabolism, Neonatal brain injury, medicine.disease, Oligodendrocyte, Rats, Oxygen, 030104 developmental biology, Diffusion Magnetic Resonance Imaging, Receptors, Lysosphingolipid/antagonists & inhibitors/metabolism, Animals, Newborn, Lysophospholipids, White matter development, Cognition Disorders, Hyperoxia/drug therapy/pathology, 030217 neurology & neurosurgery, Oxidative stress

الوصف: Cerebral white matter injury is a leading cause of adverse neurodevelopmental outcome in prematurely born infants involving cognitive deficits in later life. Despite increasing knowledge about the pathophysiology of perinatal brain injury, therapeutic options are limited. In the adult demyelinating disease multiple sclerosis the sphingosine-1-phosphate (S1P) receptor modulating substance fingolimod (FTY720) has beneficial effects. Herein, we evaluated the neuroprotective potential of FTY720 in a neonatal model of oxygen-toxicity, which is associated with hypomyelination and impaired neuro-cognitive outcome.A single dose of FTY720 (1mg/kg) at the onset of neonatal hyperoxia (24h 80% oxygen on postnatal day 6) resulted in improvement of neuro-cognitive development persisting into adulthood. This was associated with reduced microstructural white matter abnormalities 4months after the insult. In search of the underlying mechanisms potential non-classical (i.e. lymphocyte-independent) pathways were analysed shortly after the insult, comprising modulation of oxidative stress and local inflammatory responses as well as myelination, oligodendrocyte degeneration and maturation. Treatment with FTY720 reduced hyperoxia-induced oxidative stress, microglia activation and associated pro-inflammatory cytokine expression. In vivo and in vitro analyses further revealed that oxygen-induced hypomyelination is restored to control levels, which was accompanied by reduced oligodendrocyte degeneration and enhanced maturation. Furthermore, hyperoxia-induced elevation of S1P receptor 1 (S1P1) protein expression on in vitro cultured oligodendrocyte precursor cells was reduced by activated FTY720 and protection from degeneration is abrogated after selective S1P1 blockade. Finally, FTY720s’ classical mode of action (i.e. retention of immune cells within peripheral lymphoid organs) was analysed demonstrating that FTY720 diminished circulating lymphocyte counts independent from hyperoxia. Cerebral immune cell counts remained unchanged by hyperoxia and by FTY720 treatment.Taken together, these results suggest that beneficial effects of FTY720 in neonatal oxygen-induced brain injury may be rather attributed to its anti-oxidative and anti-inflammatory capacity acting in concert with a direct protection of developing oligodendrocytes than to a modulation of peripheral lymphocyte trafficking. Thus, FTY720 might be a potential new therapeutic option for the treatment of neonatal brain injury through reduction of white matter damage.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::107efda10ac14301a02fe7283fc9f3ef
https://www.ncbi.nlm.nih.gov/pubmed/26456693

المؤلفون: Bäckhed, Fredrik, 1973, Alsen, B., Roche, N., Angstrom, J., von Euler, A., Breimer, Michael, 1951, Westerlund-Wikstrom, B., Teneberg, Susann, 1955, Richter-Dahlfors, A.

المصدر: Journal of Biological Chemistry. 277(20):18198-205

مصطلحات موضوعية: Microbiology in the medical area, Mikrobiologi inom det medicinska området, Animals, Bacterial Adhesion, Chromatography, Thin Layer, Dogs, Escherichia coli, Escherichia coli Infections/ pathology, Galactosylceramides/metabolism, Glycosphingolipids/ metabolism, Humans, Interleukin-8/biosynthesis, Magnetic Resonance Spectroscopy, Mucous Membrane/pathology, Rats, Receptors, Immunologic/metabolism, Sphingosine/ analogs & derivatives/metabolism, Trihexosylceramides/metabolism, Urinary Tract/microbiology/ pathology, Urinary Tract Infections/microbiology/ pathology

الوصف: Bacterial adherence to mucosal cells is a key virulence trait of pathogenic bacteria. The type 1 fimbriae and the P-fimbriae of Escherichia coli have both been described to be important for the establishment of urinary tract infections. While P-fimbriae recognize kidney glycosphingolipids carrying the Galalpha4Gal determinant, type 1 fimbriae bind to the urothelial mannosylated glycoproteins uroplakin Ia and Ib. The F1C fimbriae are one additional type of fimbria correlated with uropathogenicity. Although it was identified 20 years ago its receptor has remained unidentified. Here we report that F1C-fimbriated bacteria selectively interact with two minor glycosphingolipids isolated from rat, canine, and human urinary tract. Binding-active compounds were isolated and characterized as galactosylceramide, and globotriaosylceramide, both with phytosphingosine and hydroxy fatty acids. Comparison with reference glycosphingolipids revealed that the receptor specificity is dependent on the ceramide composition. Galactosylceramide was present in the bladder, urethers, and kidney while globotriaosylceramide was present only in the kidney. Using a functional assay, we demonstrate that binding of F1C-fimbriated Escherichia coli to renal cells induces interleukin-8 production, thus suggesting a role for F1C-mediated attachment in mucosal defense against bacterial infections.

URL الوصول: https://gup.ub.gu.se/publication/105088

المؤلفون: Thierry Berney, Rahel A Sibler, Jan A. Ehses, Spiros Georgopoulos, Lucia Rohrer, Richard Prazak, Sabine Rütti, Marc Y. Donath, Nadja Niclauss, Daniel T. Meier, Arnold von Eckardstein

المساهمون: University of Zurich

المصدر: Endocrinology, Vol. 150, No 10 (2009) pp. 4521-30

مصطلحات موضوعية: Male, CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism, Interleukin-1beta, 10265 Clinic for Endocrinology and Diabetology, CASP8 and FADD-Like Apoptosis Regulating Protein, Nitric Oxide Synthase Type II, Apoptosis, Sphingosine/analogs & derivatives/metabolism, Mice, Endocrinology, Sphingosine, Insulin-Secreting Cells, 540 Chemistry, Insulin Secretion, Glucose/metabolism, Insulin, Receptor, Cells, Cultured, 10038 Institute of Clinical Chemistry, Mice, Knockout, ddc:617, biology, Middle Aged, Scavenger Receptors, Class B, 1310 Endocrinology, Lipoproteins, LDL, 10076 Center for Integrative Human Physiology, lipids (amino acids, peptides, and proteins), Apolipoprotein A1, Female, Lipoproteins, HDL, Nitric Oxide Synthase Type II/metabolism, Insulin-Secreting Cells/physiology, Lipoproteins, LDL/physiology, medicine.medical_specialty, Programmed cell death, Cell Survival, Receptors, LDL/metabolism, 610 Medicine & health, Lipoproteins, HDL/physiology, Apolipoprotein A-I/metabolism, Internal medicine, medicine, Animals, Humans, Scavenger Receptors, Class B/metabolism, fas Receptor, Scavenger receptor, Cell Proliferation, Insulin/secretion, Apolipoprotein A-I, Lysophospholipids/metabolism, Sphingolipid, Mice, Inbred C57BL, Glucose, Receptors, LDL, Antigens, CD95/metabolism, Interleukin-1beta/metabolism, LDL receptor, biology.protein, 570 Life sciences, Lysophospholipids, Lipoprotein

الوصف: A low high-density lipoprotein (HDL) plasma concentration and the abundance of small dense low-density lipoproteins (LDL) are risk factors for developing type 2 diabetes. We therefore investigated whether HDL and LDL play a role in the regulation of pancreatic islet cell apoptosis, proliferation, and secretory function. Isolated mouse and human islets were exposed to plasma lipoproteins of healthy human donors. In murine and human β-cells, LDL decreased both proliferation and maximal glucose-stimulated insulin secretion. The comparative analysis of β-cells from wild-type and LDL receptor-deficient mice revealed that the inhibitory effect of LDL on insulin secretion but not proliferation requires the LDL receptor. HDL was found to modulate the survival of both human and murine islets by decreasing basal as well as IL-1β and glucose-induced apoptosis. IL-1β-induced β-cell apoptosis was also inhibited in the presence of either the delipidated protein or the deproteinated lipid moieties of HDL, apolipoprotein A1 (the main protein component of HDL), or sphingosine-1-phosphate (a bioactive sphingolipid mostly carried by HDL). In murine β-cells, the protective effect of HDL against IL-1β-induced apoptosis was also observed in the absence of the HDL receptor scavenger receptor class B type 1. Our data show that both LDL and HDL affect function or survival of β-cells and raise the question whether dyslipidemia contributes to β-cell failure and hence the manifestation and progression of type 2 diabetes mellitus.

وصف الملف: Ruetti_vonEckardstein_Endocrinology_09_V.pdf - application/pdf; 4521.full.pdf - application/pdf

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25513697d42dc2ebe84188aa87b57fd7

المصدر: Fertility and sterility, 97 (4

مستخلص: To investigate key genes expression of the sphingosine-1-phosphate pathway in endometriotic tissues.
Journal Article
SCOPUS: ar.j
info:eu-repo/semantics/published

مصطلحات الفهرس: Médecine pathologie humaine, Aldehyde-Lyases -- genetics, Analysis of Variance, Case-Control Studies, Endometriosis -- genetics -- metabolism, Endometrium -- chemistry, Female, Hospitals, University, Humans, Immunohistochemistry, Lysophospholipids -- metabolism, Membrane Proteins -- genetics, Ovarian Diseases -- genetics -- metabolism, Paris, Phosphoric Monoester Hydrolases -- genetics, Phosphotransferases (Alcohol Group Acceptor) -- genetics, RNA, Messenger -- analysis, Real-Time Polymerase Chain Reaction, Receptors, Lysosphingolipid -- analysis -- genetics, Reverse Transcriptase Polymerase Chain Reaction, Sphingosine -- analogs & derivatives -- metabolism, apoptosis, Endometriosis, S1P, sphingosine pathway, sphingosine-1-phosphate, info:eu-repo/semantics/article, info:ulb-repo/semantics/articlePeerReview, info:ulb-repo/semantics/openurl/article

URL: https://dipot.ulb.ac.be/dspace/bitstream/2013/156127/3/Elsevier_141041.pdf
http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/156127
http://worldcat.org/search?q=on:EQY+http://difusion-oai.ulb.ac.be/oai/request+DCG_ENTIRE_REPOSITORY+CNTCOLL

المصدر: Fertility and sterility, 97 (4

مستخلص: To investigate key genes expression of the sphingosine-1-phosphate pathway in endometriotic tissues.
Journal Article
SCOPUS: ar.j
info:eu-repo/semantics/published

مصطلحات الفهرس: Médecine pathologie humaine, Aldehyde-Lyases -- genetics, Analysis of Variance, Case-Control Studies, Endometriosis -- genetics -- metabolism, Endometrium -- chemistry, Female, Hospitals, University, Humans, Immunohistochemistry, Lysophospholipids -- metabolism, Membrane Proteins -- genetics, Ovarian Diseases -- genetics -- metabolism, Paris, Phosphoric Monoester Hydrolases -- genetics, Phosphotransferases (Alcohol Group Acceptor) -- genetics, RNA, Messenger -- analysis, Real-Time Polymerase Chain Reaction, Receptors, Lysosphingolipid -- analysis -- genetics, Reverse Transcriptase Polymerase Chain Reaction, Sphingosine -- analogs & derivatives -- metabolism, apoptosis, Endometriosis, S1P, sphingosine pathway, sphingosine-1-phosphate, info:eu-repo/semantics/article, info:ulb-repo/semantics/articlePeerReview, info:ulb-repo/semantics/openurl/article

URL: https://dipot.ulb.ac.be/dspace/bitstream/2013/156127/3/Elsevier_141041.pdf
http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/156127
http://worldcat.org/search?q=on:EQY+http://difusion-oai.ulb.ac.be/oai/request+DCG_ENTIRE_REPOSITORY+CNTCOLL