Ceramides: Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.Sphingosine N-Acyltransferase: An enzyme that catalyzes the acyltransferase of SPHINGOSINE to N-acylsphingosine using acyl-COENZYME A as donor and COENZYME A as acceptor. The enzyme is mainly localized in the MITOCHONDRIA.Sphingolipids: A class of membrane lipids that have a polar head and two nonpolar tails. They are composed of one molecule of the long-chain amino alcohol sphingosine (4-sphingenine) or one of its derivatives, one molecule of a long-chain acid, a polar head alcohol and sometimes phosphoric acid in diester linkage at the polar head group. (Lehninger et al, Principles of Biochemistry, 2nd ed)Sphingosine: An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed)Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)Sphingomyelins: A class of sphingolipids found largely in the brain and other nervous tissue. They contain phosphocholine or phosphoethanolamine as their polar head group so therefore are the only sphingolipids classified as PHOSPHOLIPIDS.Glucosylceramides: Cerebrosides which contain as their polar head group a glucose moiety bound in glycosidic linkage to the hydroxyl group of ceramides. Their accumulation in tissue, due to a defect in beta-glucosidase, is the cause of Gaucher's disease.Alkaline Ceramidase: A ceramidase subtype that is active at alkaline pH. It is found at high levels within the SMALL INTESTINE.Sphingomyelin Phosphodiesterase: An enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide (N-acylsphingosine) plus choline phosphate. A defect in this enzyme leads to NIEMANN-PICK DISEASE. EC 3.1.4.12.Ichthyosiform Erythroderma, Congenital: Designation for several severe forms of ichthyosis, present at birth, that are characterized by hyperkeratotic scaling. Infants may be born encased in a collodion membrane which begins shedding within 24 hours. This is followed in about two weeks by persistent generalized scaling. The forms include bullous (HYPERKERATOSIS, EPIDERMOLYTIC), non-bullous (ICHTHYOSIS, LAMELLAR), wet type, and dry type.Fumonisins: A group of MYCOTOXINS found in CORN contaminated with FUSARIUM fungus. They are chains of about 20 carbons with acidic ester, acetylamino and sometimes other substituents. They inhibit ceramide synthetase conversion of SPHINGOLIPIDS to CERAMIDES.Cerebrosides: Neutral glycosphingolipids that contain a monosaccharide, normally glucose or galactose, in 1-ortho-beta-glycosidic linkage with the primary alcohol of an N-acyl sphingoid (ceramide). In plants the monosaccharide is normally glucose and the sphingoid usually phytosphingosine. In animals, the monosaccharide is usually galactose, though this may vary with the tissue and the sphingoid is usually sphingosine or dihydrosphingosine. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1st ed)Ceramidases: Amidohydrolases that are specific for the cleavage of the N-acyl linkage of CERAMIDES. Ceramidases are classified as acidic, neutral or basic according to the optimal pH with which they function.Serine C-Palmitoyltransferase: A key enzyme in SPHINGOLIPIDS biosynthesis, this enzyme catalyzes the pyridoxal-5'-phosphate-dependent condensation of L-SERINE and PALMITOYL COENZYME A to 3-dehydro-D-sphinganine. The enzyme consists of two different subunits.Chromatography, Thin Layer: Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Enzyme Assays: Methods used to measure the relative activity of a specific enzyme or its concentration in solution. Typically an enzyme substrate is added to a buffer solution containing enzyme and the rate of conversion of substrate to product is measured under controlled conditions. Many classical enzymatic assay methods involve the use of synthetic colorimetric substrates and measuring the reaction rates using a spectrophotometer.Glycosphingolipids: Lipids containing at least one monosaccharide residue and either a sphingoid or a ceramide (CERAMIDES). They are subdivided into NEUTRAL GLYCOSPHINGOLIPIDS comprising monoglycosyl- and oligoglycosylsphingoids and monoglycosyl- and oligoglycosylceramides; and ACIDIC GLYCOSPHINGOLIPIDS which comprises sialosylglycosylsphingolipids (GANGLIOSIDES); SULFOGLYCOSPHINGOLIPIDS (formerly known as sulfatides), glycuronoglycosphingolipids, and phospho- and phosphonoglycosphingolipids. (From IUPAC's webpage)Epidermis: The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of EPITHELIUM: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).I Blood-Group System: A blood group related both to the ABO and P systems that includes several different antigens found in most people on erythrocytes, in milk, and in saliva. The antibodies react only at low temperatures.Chromatography, Gas: Fractionation of a vaporized sample as a consequence of partition between a mobile gaseous phase and a stationary phase held in a column. Two types are gas-solid chromatography, where the fixed phase is a solid, and gas-liquid, in which the stationary phase is a nonvolatile liquid supported on an inert solid matrix.Spinocerebellar Degenerations: A heterogenous group of degenerative syndromes marked by progressive cerebellar dysfunction either in isolation or combined with other neurologic manifestations. Sporadic and inherited subtypes occur. Inheritance patterns include autosomal dominant, autosomal recessive, and X-linked.Water Loss, Insensible: Loss of water by diffusion through the skin and by evaporation from the respiratory tract.Fatty Acids: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Lipidoses: Conditions characterized by abnormal lipid deposition due to disturbance in lipid metabolism, such as hereditary diseases involving lysosomal enzymes required for lipid breakdown. They are classified either by the enzyme defect or by the type of lipid involved.Acid Ceramidase: A ceramidase subtype that is active at acid pH. It plays an important role in sphingolipid degradation by catalyzing the lysosomal hydrolysis of ceramide to sphingosine and free fatty acid. Inherited deficiency of acid ceramidase activity results in FARBER LIPOGRANULOMATOSIS.Activating Transcription Factor 6: One of the BASIC-LEUCINE ZIPPER TRANSCRIPTION FACTORS that is synthesized as a membrane-bound protein in the ENDOPLASMIC RETICULUM. In response to endoplasmic reticulum stress it translocates to the GOLGI APPARATUS. It is activated by PROTEASES and then moves to the CELL NUCLEUS to regulate GENETIC TRANSCRIPTION of GENES involved in the unfolded protein response.Neutral Glycosphingolipids: A subclass of GLYCOSPHINGOLIPIDS containing one or more sugars within their head group connected directly to a ceramide moiety. They consist of monoglycosyl-, and oligoglycosylsphingoids and monoglycosyl- and oligoglycosylceramides.Lipids: A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Sulfoglycosphingolipids: GLYCOSPHINGOLIPIDS with a sulfate group esterified to one of the sugar groups.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Hydroxy Acids: Organic compounds containing both the hydroxyl and carboxyl radicals.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Golgi Apparatus: A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)Amino Alcohols: Compounds possessing both a hydroxyl (-OH) and an amino group (-NH2).Glycolipids: Any compound containing one or more monosaccharide residues bound by a glycosidic linkage to a hydrophobic moiety such as an acylglycerol (see GLYCERIDES), a sphingoid, a ceramide (CERAMIDES) (N-acylsphingoid) or a prenyl phosphate. (From IUPAC's webpage)Lysophospholipids: Derivatives of PHOSPHATIDIC ACIDS that lack one of its fatty acyl chains due to its hydrolytic removal.Mice, Hairless: Mutant strains of mice that produce little or no hair.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.G(M3) Ganglioside: A ganglioside present in abnormally large amounts in the brain and liver due to a deficient biosynthetic enzyme, G(M3):UDP-N-acetylgalactosaminyltransferase. Deficiency of this enzyme prevents the formation of G(M2) ganglioside from G(M3) ganglioside and is the cause of an anabolic sphingolipidosis.Cell Line, Tumor: A cell line derived from cultured tumor cells.DiglyceridesGlucosylceramidase: A glycosidase that hydrolyzes a glucosylceramide to yield free ceramide plus glucose. Deficiency of this enzyme leads to abnormally high concentrations of glucosylceramide in the brain in GAUCHER DISEASE. EC 3.2.1.45.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Fatty Alcohols: Usually high-molecular-weight, straight-chain primary alcohols, but can also range from as few as 4 carbons, derived from natural fats and oils, including lauryl, stearyl, oleyl, and linoleyl alcohols. They are used in pharmaceuticals, cosmetics, detergents, plastics, and lube oils and in textile manufacture. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Galactosylceramides: Cerebrosides which contain as their polar head group a galactose moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in beta-galactosidase, is the cause of galactosylceramide lipidosis or globoid cell leukodystrophy.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Galactosylgalactosylglucosylceramidase: An enzyme that catalyzes the hydrolysis of a ceramidetrihexoside to a ceramidedihexoside plus galactose.Spectrometry, Mass, Electrospray Ionization: A mass spectrometry technique used for analysis of nonvolatile compounds such as proteins and macromolecules. The technique involves preparing electrically charged droplets from analyte molecules dissolved in solvent. The electrically charged droplets enter a vacuum chamber where the solvent is evaporated. Evaporation of solvent reduces the droplet size, thereby increasing the coulombic repulsion within the droplet. As the charged droplets get smaller, the excess charge within them causes them to disintegrate and release analyte molecules. The volatilized analyte molecules are then analyzed by mass spectrometry.Neutral Ceramidase: A ceramidase subtype that is active at neutral pH. It is found at high levels within the SMALL INTESTINE and in the BRAIN.Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Phospholipase D: An enzyme found mostly in plant tissue. It hydrolyzes glycerophosphatidates with the formation of a phosphatidic acid and a nitrogenous base such as choline. This enzyme also catalyzes transphosphatidylation reactions. EC 3.1.4.4.Lactosylceramides: Glycosphingolipids which contain as their polar head group a lactose moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in lactosylceramide beta-galactosidase, is the cause of lactosylceramidosis.Optical Rotation: The rotation of linearly polarized light as it passes through various media.Sphingolipidoses: A group of inherited metabolic disorders characterized by the intralysosomal accumulation of SPHINGOLIPIDS primarily in the CENTRAL NERVOUS SYSTEM and to a variable degree in the visceral organs. They are classified by the enzyme defect in the degradation pathway and the substrate accumulation (or storage). Clinical features vary in subtypes but neurodegeneration is a common sign.
  • The encoded enzyme synthesizes 18-carbon (C18) ceramide in brain neurons. (genecards.org)
  • Suppression of either enzyme using inhibitors or small interfering RNA potentiated the decreased viability, induction of cell death, and ceramide accumulation induced by R-MA treatment. (aacrjournals.org)
  • When CerS3 was overexpressed in HEK-293T cells, an increased production of C 18 and C 24 ceramide species was observed ( 10 ), whereas overexpression of CerS6 showed that the enzyme preferably synthesized the long-chain ceramide species C 14 and C 16 ceramide ( 11 ). (aacrjournals.org)
  • To determine whether induction of endogenous CerS1 is important in mediating mitochondrial tension signaling, we treated UM-SCC-22A cells using the known tension inducer, SoSe (5 M, 3 hours), and assessed its results on CerS1 mRNA/protein LY2109761 enzyme inhibitor great quantity, mitophagy, and cell loss of life. (antibodyassay.com)
  • LY2109761 enzyme inhibitor Brief hairpinCmediated RNA (shRNA)Cmediated knockdown (95%) of CerS1 (fig. S1G) nearly totally prevented SoSe-mediated LC3-II development and mitophagy (Fig. 1G, still left and right sections). (antibodyassay.com)
  • The PERMIT protein brings the enzyme that produces ceramide into the mitochondria, thus reducing cellular buildup. (prohealthlongevity.com)
  • In response to stress, the cell begins to make the enzyme responsible for producing ceramide. (prohealthlongevity.com)
  • The enzyme, known as CerS1, can then mass-produce ceramide at the precise location needed for mitochondrial regulation. (prohealthlongevity.com)
  • SMS is an enzyme that catalyzes the transfer of the phosphocholine head group of phosphatidylcholine to ceramide, generating SM ( Table 1 ). (molcells.org)
  • Expression of LASS1/CerS1 increases the sensitivity to all the drugs tested, whereas LASS5/CerS5 only increases sensitivity to doxorubicin and vincristine. (illinois.edu)
  • In a recent publication in Annals of Neurology, mutations in CERS1 , coding for ceramide synthetase, are identified in a family with progressive myoclonus epilepsy - and provides an unexpected linked between a group of storage disorders such as Niemann-Pick disease and Tay-Sachs disease and progressive myoclonus epilepsies . (epilepsygenetics.net)
  • Fig 2A and B). Data showed that I2PP2A/SET is overexpressed in 70% (7/10, n = 10) of these tumours (Fig 2A), whereas C18-ceramide and CerS1 mRNA levels are decreased (∼50%) in the majority of tumours (8/10, n = 10) compared to non-cancerous lung tissues (Fig 2C and D, respectively). (nih.gov)
  • The masses of the ceramide subspecies C 16 , C 18 , C 24 , and C 24:1 were normalized to lipid phosphate. (aacrjournals.org)
  • We found, through genetic manipulation and lipid analysis, that biosynthesis of ceramide, particularly those with longer fatty acid side chains, critically impacts animal survival during L1 diapause. (genetics.org)
  • Ceramide and the metabolites participate in various cellular events as lipid mediators. (jle.com)
  • The Ogretmen laboratory studies the signaling lipid ceramide and its role in many biological pathways, including cancer biology. (musc.edu)
  • Thus, these enzymes and their lipid products (ceramides) do not have overlapping functions, but have distinct activities and targets, based probably on their cellular location. (musc.edu)
  • This finding underlies the essential role of enzymes regulating either the synthesis (CERS1) or degradation (ASAH1) of ceramide, and the link between defects in ceramide metabolism and PME. (jle.com)
  • In the context of cancer, some ceramides, and the enzymes that produce them, contribute to tumor growth because they provide a critical component of the plasma membrane, enabling cells to divide. (musc.edu)
  • After that, the common metabolic item, ceramide, generated by either path is definitely additional deacylated by A-CDase to generate sphingosine and free of charge fatty acidity that can keep the lysosomes and enter into the cytosol [2,3, (exposed-skin-care.net)
  • The sphingoid base can be bound to a fatty acid via an amide link to produce ceramide (Cer). (jci.org)
  • Genetic and expression analyses indicate that ceramide is required for maintaining the proper expression of previously characterized starvation-responsive genes, genes that are regulated by the IIS pathway and tumor suppressor Rb, and genes responsive to pathogen. (genetics.org)
  • In addition, pro-ceramide genes, which promote insulin resistance, were increased in livers and brains of rats exposed to NDEA, HFD, or both. (biomedcentral.com)
  • Ceramide levels are elevated in mantle cell lymphoma (MCL) cells following treatment with cannabinoids. (aacrjournals.org)
  • Here we report a phase II clinical trial, which was designed to test a novel hypothesis that treatment with gemcitabine (GEM)/doxorubicin (DOX) would be efficacious via reconstitution of C 18 -ceramide signaling in head and neck squamous cell carcinoma (HNSCC) patients for whom first-line platinum-based therapy failed. (aacrjournals.org)