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Ceramide

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https://www.readbyqxmd.com/read/28819979/the-influence-of-a-novel-dimeric-ceramide-molecule-on-the-nanostructure-and-the-thermotropic-phase-behavior-of-a-stratum-corneum-model-mixture
#1
Sören Stahlberg, Adina Eichner, Stefan Sonnenberger, Andrej Kovacik, Stefan Lange, Thomas Schmitt, Bruno Demé, Thomas Hauss, Bodo Dobner, Reinhard H H Neubert, Daniel Huster
The stratum corneum (SC) is the outermost layer of the skin and composed of a multilayered assembly of mostly ceramids (Cer), free fatty acids, cholesterol (Chol), and cholesterol sulphate (Chol-S). Due to the tight packing of these lipids, the SC features unique barrier properties defending the skin from environmental influences. Under pathological conditions, where the skin barrier function is compromised, topical application of molecules that rigidify the SC may lead to a restored barrier function. To this end, molecules are required that incorporate into the SC and bring back the original rigidity of the skin barrier...
August 18, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28815522/ceramide-transport-from-the-endoplasmic-reticulum-to-the-trans-golgi-region-at-organelle-membrane-contact-sites
#2
Kentaro Hanada
Lipids are the major constituents of all cell membranes and play dynamic roles in organelle structure and function. Although the spontaneous transfer of lipids between different membranes rarely occurs, lipids are appropriately transported between different organelles for their metabolism and to exert their functions in living cells. Proteins that have the biochemical capability to catalyze the intermembrane transfer of lipids are called lipid transfer proteins (LTPs). All organisms possess many types of LTPs...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28815463/the-many-faces-and-phases-of-ceramide-and-sphingomyelin-i-single-lipids
#3
REVIEW
María Laura Fanani, Bruno Maggio
Ceramides, the simplest kind of two-chained sphingolipids, contain a single hydroxyl group in position 1 of the sphingoid base. Sphingomyelins further contain a phosphocholine group at the OH of position 1 of ceramide. Ceramides and sphingomyelins show a variety of species depending on the fatty acyl chain length, hydroxylation, and unsaturation. Because of the relatively high transition temperature of sphingomyelin compared to lecithin and, particularly, of ceramides with 16:0-18:0 saturated chains, a widespread idea on their functional importance refers to formation of rather solid domains enriched in sphingomyelin and ceramide...
August 16, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28814641/ceramide-activation-of-rhoa-rho-kinase-impairs-actin-polymerization-during-aggregated-ldl-catabolism
#4
Rajesh K Singh, Abigail S Haka, Alexandria Brumfield, Inna Grosheva, Priya Bhardwaj, Harvey F Chin, Yuquan Xiong, Timothy Hla, Frederick R Maxfield
Macrophages use an extracellular, hydrolytic compartment formed by local actin polymerization to digest aggregated LDL (agLDL). Catabolism of agLDL promotes foam cell formation and creates an environment rich in LDL catabolites including cholesterol and ceramide. Increased ceramide levels are present in lesional LDL, but the effect of ceramide on macrophage pro-atherogenic processes remains unknown. Here, we show that macrophages accumulate ceramide in atherosclerotic lesions. Using macrophages from Sphingosine Kinase 2 knockout (SK2KO) mice to mimic ceramide rich conditions of atherosclerotic lesions, we show that SK2KO macrophages display impaired actin polymerization and foam cell formation in response to contact with agLDL...
August 16, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28812237/pharmacological-effects-on-ceroid-lipofuscin-and-neuronal-structure-in-cln3-%C3%A2-ex7-8-mouse-brain-cultures
#5
Douglas E Brenneman, David A Pearce, Attila Kovacs, Shawn DeFrees
Juvenile Batten disease (JBD) is an inherited disorder that is characterized by the development of blindness, seizures, and progressive motor, psychiatric, and cognitive impairment. A model of JBD expressing the predominant human mutation (Cln3 (∆ex7/8) ) has been explored. Dissociated brain cultures from Cln3 (∆ex7/8) knock-in mice were compared to wild type (WT) for effects on granules of ceroid lipofuscin (CL) and neuronal structure. Utilizing high content image analysis of CL granules identified with antibodies to mitochondrial ATP synthase subunit c or tripeptidyl peptidase-1, significant increases in the areas for both immunoreactive granules were observed in Cln3 (∆ex7/8) cultures in comparison to WT...
August 15, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28808666/lipidomic-evaluation-of-feline-neurologic-disease-after-aav-gene-therapy
#6
Heather L Gray-Edwards, Xuntian Jiang, Ashley N Randle, Amanda R Taylor, Taylor L Voss, Aime K Johnson, Victoria J McCurdy, Miguel Sena-Esteves, Daniel S Ory, Douglas R Martin
GM1 gangliosidosis is a fatal lysosomal disorder, for which there is no effective treatment. Adeno-associated virus (AAV) gene therapy in GM1 cats has resulted in a greater than 6-fold increase in lifespan, with many cats remaining alive at >5.7 years of age, with minimal clinical signs. Glycolipids are the principal storage product in GM1 gangliosidosis whose pathogenic mechanism is not completely understood. Targeted lipidomics analysis was performed to better define disease mechanisms and identify markers of disease progression for upcoming clinical trials in humans...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28806500/doxepin-mitigates-noise-induced-neuronal-damage-in-primary-auditory-cortex-of-mice-via-suppression-of-acid-sphingomyelinase-ceramide-pathway
#7
Yu-Ting Su, Xing-Xing Meng, Xi Zhang, Yi-Bin Guo, Hai-Jun Zhang, Yao-Ping Cheng, Xiao-Ping Xie, Yao-Ming Chang, Jun-Xiang Bao
Neuronal damage in primary auditory cortex (A1) underlies complex manifestations of noise exposure, prevention of which is critical for health maintenance. Acid sphingomyelinase (ASM) catalyzes generation of ceramide (Cer) which if over-activated mediates neuronal disorders in various diseases. Tricyclic antidepressants (TCAs), by restraining ASM/Cer, benefits multiple neuronal anomalies, so we aimed to elucidate the effect of TCA on noise induced hearing loss and auditory cortex derangement, unraveling mechanism involved...
August 14, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28800942/plasma-and-ovarian-tissue-sphingolipids-profiling-in-patients-with-advanced-ovarian-cancer
#8
Paweł Knapp, Lubomir Bodnar, Agnieszka Błachnio-Zabielska, Magdalena Świderska, Adrian Chabowski
PURPOSE: The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). METHODS: Seventy-four patients with ovarian cancer were enrolled...
August 8, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28798382/chronic-low-level-expression-of-hiv-1-tat-promotes-a-neurodegenerative-phenotype-with-aging
#9
Alex M Dickens, Seung Wan Yoo, Alfred C Chin, Jiadi Xu, Tory P Johnson, Amanda L Trout, Kurt F Hauser, Norman J Haughey
The widespread use of combinational antiretroviral therapies (cART) in developed countries has changed the course of Human Immunodeficiency Virus (HIV) infection from an almost universally fatal disease to a chronic infection for the majority of individuals. Although cART has reduced the severity of neurological damage in HIV-infected individuals, the likelihood of cognitive impairment increases with age, and duration of infection. As cART does not suppress the expression of HIV non-structural proteins, it has been proposed that a constitutive production of HIV regulatory proteins in infected brain cells may contribute to neurological damage...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797762/ceramide-enhances-cox-2-expression-and-vsmc-contractile-hyperreactivity-via-er-stress-signal-activation
#10
Huina Zhang, Juanfen Li, Linghai Li, Pingsheng Liu, Yongxiang Wei, Zongjie Qian
Ceramide accumulation in blood vessels has been attributed to vascular dysfunction in progressive vascular complications in metabolic diseases. The present study showed that ceramide pretreatment promoted PE-induced vasoconstriction in rat endothelium-denuded vascular rings in a time- and dose-dependent manner. Endoplasmic reticulum (ER) stress inhibitors, 4-PBA and TUDCA, COX-2 inhibitors, Celecoxib and NS398, as well as PGE2 receptor antagonist AH-6809 attenuated ceramide-promoted vascular hyperreactivity...
August 7, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28796418/role-of-the-gm1-ganglioside-oligosaccharide-portion-in-the-trka-dependent-neurite-sprouting-in-neuroblastoma-cells
#11
Elena Chiricozzi, Diego Yuri Pomè, Margherita Maggioni, Erika Di Biase, Chiara Parravicini, Luca Palazzolo, Nicoletta Loberto, Ivano Eberini, Sandro Sonnino
GM1 ganglioside (II(3) NeuAc-Gg4 Cer) is known to promote neurite formation in neuroblastoma cells by activating TrkA-MAPK pathway. The molecular mechanism by which GM1 is involved in the neurodifferentiation process is still unknown, however, in vitro and in vivo evidences have suggested that the oligosaccharide portion of this ganglioside could be involved. Here, we report that, similarly to the entire GM1 molecule, its oligosaccharide II(3) NeuAc-Gg4, rather than its ceramide (Cer) portion is responsible for the neurodifferentiation process by augmenting neurite elongation and increasing the neurofilament protein expression in murine neuroblastoma cells, Neuro2a...
August 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28795851/selective-induction-of-apoptosis-in-mcf7-cancer-cell-by-targeted-liposomes-functionalized-with-mannose-6-phosphate
#12
Cristina Minnelli, Laura Cianfruglia, Emiliano Laudadio, Roberta Galeazzi, Michela Pisani, Emanuela Crucianelli, Davide Bizzaro, Tatiana Armeni, Giovanna Mobbili
Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalization and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28795093/anandamide-ceramide-interactions-in-a-membrane-environment-molecular-dynamic-simulations-data
#13
Coralie Di Scala, Morgane Mazzarino, Nouara Yahi, Karine Varini, Nicolas Garmy, Jacques Fantini, Henri Chahinian
Anandamide is a lipid neurotransmitter that interacts with various plasma membrane lipids. The data here consists of molecular dynamics simulations of anandamide, C18-ceramide and cholesterol performed in vacuo and within a hydrated palmitoyl-oleoyl-phosphatidylcholine (POPC)/cholesterol membrane. Several models of anandamide/cholesterol and anandamide/ceramide complexes are presented. The energy of interaction and the nature of the intermolecular forces involved in each of these complexes are detailed. The impact of water molecules hydrating the POPC/cholesterol membrane for the stability of the anandamide/cholesterol and anandamide/ceramide complexes is also analyzed...
October 2017: Data in Brief
https://www.readbyqxmd.com/read/28793293/triggering-of-eryptosis-the-suicidal-erythrocyte-death-by-mammalian-target-of-rapamycin-mtor-inhibitor-temsirolimus
#14
Abdulla Al Mamun Bhuyan, Hang Cao, Florian Lang
BACKGROUND/AIMS: The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is utilized for the treatment of malignancy. Temsirolimus is at least in part effective by triggering suicidal tumor cell death. The most common side effect of temsirolimus treatment is anemia. At least in theory, the anemia following temsirolimus treatment could result from stimulation of eryptosis, the suicidal erythrocyte death. Hallmarks of eryptosis include cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface...
July 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28775166/aneuploid-cell-survival-relies-upon-sphingolipid-homeostasis
#15
Yun-Chi Tang, Hui Yuwen, Kaiying Wang, Peter M Bruno, Kevin Bullock, Amy A Deik, Stefano Santaguida, Marianna Trakala, Sarah J Pfau, Na Zhong, Tao Huang, Lan Wang, Clary B Clish, Michael T Hemann, Angelika Amon
Aneuploidy, a hallmark of cancer cells, poses an appealing opportunity for cancer treatment and prevention strategies. Using a cell-based screen to identify small molecules that could selectively kill aneuploid cells, we identified the compound N-[2-hydroxy-1-(4-morpholinylmethyl)-2-phenylethyl]-decanamide monohydrochloride (DL-PDMP), an antagonist of UDP-glucose ceramide glucosyltransferase. DL-PDMP selectively inhibited proliferation of aneuploid primary mouse embryonic fibroblasts and aneuploid colorectal cancer cells...
August 3, 2017: Cancer Research
https://www.readbyqxmd.com/read/28774589/biallelic-mutations-in-kdsr-disrupt-ceramide-synthesis-and-result-in-a-spectrum-of-keratinization-disorders-associated-with-thrombocytopenia
#16
Takuya Takeichi, Antonio Torrelo, John Y W Lee, Yusuke Ohno, María Luisa Lozano, Akio Kihara, Lu Liu, Yuka Yasuda, Junko Ishikawa, Takatoshi Murase, Ana Belén Rodrigo, Pablo Fernández-Crehuet, Yoichiro Toi, Jemima Mellerio, José Rivera, Vicente Vicente, David P Kelsell, Yutaka Nishimura, Yusuke Okuno, Daiei Kojima, Yasushi Ogawa, Kazumitsu Sugiura, Michael A Simpson, W H Irwin McLean, Masashi Akiyama, John A McGrath
Mutations in ceramide biosynthesis pathways have been implicated in a few Mendelian disorders of keratinization although ceramides are known to have key roles in several biological processes in skin and other tissues. Using whole-exome sequencing in four probands with undiagnosed skin hyperkeratosis/ichthyosis, we identified compound heterozygosity for mutations in KDSR, encoding an enzyme in the de novo synthesis pathway of ceramides. Two individuals had hyperkeratosis confined to palms and soles as well as anogenital skin, whereas the other two had more severe, generalized harlequin ichthyosis-like skin...
July 31, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28770378/comprehensive-quantitation-using-two-stable-isotopically-labeled-species-and-direct-detection-of-n-acyl-moiety-of-sphingomyelin
#17
Kotaro Hama, Yuko Fujiwara, Hidetsugu Tabata, Hideyo Takahashi, Kazuaki Yokoyama
Sphingomyelin (ceramide-phosphocholine, CerPCho) is a common sphingolipid in mammalian cells and is composed of phosphorylcholine and ceramide as polar and hydrophobic components, respectively. In this study, a qualitative liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS/MS) analysis is proposed in which CerPCho structures were assigned based on product ion spectra corresponding to sphingosylphosphorylcholine and N-acyl moieties. From MS/MS/MS analysis of CerPCho, we observed product ion spectra of the N-acyl fatty acids as [RCO2](-) ions as well as sphingosylphosphorylcholine...
August 2, 2017: Lipids
https://www.readbyqxmd.com/read/28768533/progression-of-pathology-in-pink1-deficient-mouse-brain-from-splicing-via-ubiquitination-er-stress-and-mitophagy-changes-to-neuroinflammation
#18
Sylvia Torres-Odio, Jana Key, Hans-Hermann Hoepken, Júlia Canet-Pons, Lucie Valek, Bastian Roller, Michael Walter, Blas Morales-Gordo, David Meierhofer, Patrick N Harter, Michel Mittelbronn, Irmgard Tegeder, Suzana Gispert, Georg Auburger
BACKGROUND: PINK1 deficiency causes the autosomal recessive PARK6 variant of Parkinson's disease. PINK1 activates ubiquitin by phosphorylation and cooperates with the downstream ubiquitin ligase PARKIN, to exert quality control and control autophagic degradation of mitochondria and of misfolded proteins in all cell types. METHODS: Global transcriptome profiling of mouse brain and neuron cultures were assessed in protein-protein interaction diagrams and by pathway enrichment algorithms...
August 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28768095/investigating-the-influence-of-membrane-composition-on-protein-glycolipid-binding-using-nanodiscs-and-proxy-ligand-electrospray-ionization-mass-spectrometry
#19
Ling Han, Luis C Morales, Michele R Richards, Elena N Kitova, Simonetta Sipione, John S Klassen
This work describes a versatile analytical approach, which combines the proxy ligand electrospray ionization mass spectrometry (ESI-MS) assay and model membranes of defined composition, to quantify the influence of lipid bilayer composition on protein-glycolipid binding in vitro. To illustrate the implementation of the assay (experimental design and data analysis), affinities of the monosialoganglioside ligand GM1, incorporated into nanodiscs (NDs), for cholera toxin B subunit homopentamer (CTB5) were measured...
August 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28763689/investigation-of-novel-pharmacological-chaperones-for-gaucher-disease
#20
Buge Yilmazer, Z Begum Yagci, Emre Bakar, Burcu Ozden, Kutlu Ulgen, Elif Ozkirimli
Beta-Glucocerebrosidase (GBA) is a lysosomal protein that is responsible for the hydrolysis of glycosylceramide into glucose and ceramide. Mutations in GBA lead to the accumulation of glycosylceramide in the lysosome causing an enlargement of the spleen and the liver and skeletal deformations. This disease is called Gaucher Disease. Enzyme replacement therapies and substrate reduction methods that are used to treat Gaucher Disease fail when the disease is neuropathic because they fail to pass the blood brain barrier...
July 20, 2017: Journal of Molecular Graphics & Modelling
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