Ceramide synthase

Ceramide synthase 2

Ceramide synthase 4

Ceramide synthase 1

Synthases10

• It is expressed at highest levels in skin, leukocytes, heart and liver, although at much lower levels than other ceramide synthases. (wikipedia.org)
• Finally, N-acylation of sphinganine by ceramide synthases (CerS) generates dihydroceramide, which is subsequently converted into ceramide via dihydroceramide desaturase (DES) [ 2 ]. (clinsci.org)
• Ceramide synthases (CerS) are integral membrane proteins of the endoplasmic reticulum that catalyze the synthesis of ceramide. (wikipedia.org)
• Stiban J, Tidhar R, Futerman AH (2010) Ceramide synthases: roles in cell physiology and signaling. (wikipedia.org)
• Treatment with R-MA led to increased levels of ceramide species C 16 , C 18 , C 24 , and C 24:1 and transcriptional induction of ceramide synthases (CerS) 3 and 6. (aacrjournals.org)
• Different ceramide species are generated through the actions of ceramide synthases (CerSs), which incorporate specific acyl side chains. (garvan.org.au)
• here, caloric restriction down-regulates expression of Spt1 and Spt2 but up-regulates ceramide synthases (Cers1, Cers2). (genscript.com)
• Ben-David O, Futerman AH (2010) The role of the ceramide acyl chain length in neurodegeneration: involvement of ceramide synthases. (springer.com)
• Dephosphorylation of endogenous ceramide synthases in the mouse brain led to severely reduced activity toward the Cers2 substrates C22:0/C24:0-CoAs and modestly reduced activity toward the Cers5/6 substrate C16:0-CoA. (hokudai.ac.jp)
• These results suggest that the phosphorylation of ceramide synthases may be a key regulatory point in the control of the distribution and levels of sphingolipids of various acyl-chain lengths. (hokudai.ac.jp)

CerS48

• CerS4 synthesizes ceramides containing C18-22 fatty acids in a fumonisin B1-independent manner. (wikipedia.org)
• Unlike CerS1 and CerS5, CerS4 does not sensitize cells to chemotherapeutic drugs. (wikipedia.org)
• Upon administration of leptin, a decrease in ceramide levels was observed in rat white adipose tissue, as were expression levels of a number of genes in the sphingolipid metabolic pathway, including CerS2 and CerS4. (wikipedia.org)
• METHODS: CerS isoforms CerS1, CerS2, CerS4, CerS5 and CerS6 were overexpressed in L6 myotubes using adenovirus, and cells were treated with palmitate and stimulated with insulin. (garvan.org.au)
• Ceramide produced by CerS4 binds to Smad7, a cellular protein that can bind the TGF-beta receptor. (musc.edu)
• These studies also demonstrate that although there are at least six different enzymes that generate ceramide CerS1-6, only one of these six enzymes, CerS4, generates ceramide that selectively inhibits cancer cell migration enhanced by TGF-beta receptor in primary cilia. (musc.edu)
• Reflecting this, we show that the activation of the p38 mitogen-activated protein (MAP) kinase is increased only by LASS1/CerS1, and not by LASS4/CerS4 or LASS5/CerS5. (illinois.edu)
• Cisplatin was shown to cause a specific translocation of LASS1/CerS1, but not LASS4/CerS4 or LASS5/CerS5, from the endoplasmic reticulum (ER) to the Golgi apparatus. (illinois.edu)

Sphingolipids11

• When overexpressed in cells is involved in the production of sphingolipids containing mainly one fatty acid donor (N-linked stearoyl- (C18) ceramide) in a fumonisin B1-independent manner (By similarity). (genecards.org)
• Sphingolipids, such as sphingomyelins, ceramides, glycosphingolipids, and sphingosine-1-phosphates (S1P) are a large group of structurally and functionally diverse molecules. (clinsci.org)
• Sphingolipids are based on a ceramide parent structure. (clinsci.org)
• This de novo pathway is the major source of ceramide in cells, and all eukaryotic cells have the capacity to produce sphingolipids in this way. (clinsci.org)
• We further interfered with the conversion of ceramide into sphingolipids that promote cell growth. (aacrjournals.org)
• Detection of sphingolipids using high-resolution matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging mass spectrometry revealed increased accumulation of long acyl chain ceramide species, and sphingosine-1-phosphate (S1P) in the EtOH group that were significantly reduced in the EtOH/SPI group. (aacrjournals.org)
• Ceramide is one of the basic building blocks of sphingolipids. (epilepsygenetics.net)
• The molecular mechanisms are not well understood, but likely involve dysregulation of membrane composition, fluidity, and permeability, which are all essentially regulated by sphingolipids, including ceramides of different chain length and saturation. (springer.com)
• CerS2 knockdown, and associated changes in several sphingolipids such as a drop in very long-chain ceramides/(dh)-ceramides, an increase in long-chain ceramides/(dh)-ceramides, and sphinganine in the colon, may weaken endogenous defense against the endogenous microbiome. (springer.com)
• Ceramide and complex sphingolipids regulate important cellular functions including cell growth, apoptosis, and signaling. (hokudai.ac.jp)
• Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have been emerging as bioactive lipids since ceramide was reported to play a role in human leukemia HL-60 cell differentiation and death. (molcells.org)

Enzyme9

• 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)

CERS9

• 3) A salvage pathway generates ceramides by recycling sphingosine via CerS, as the sphingosine is produced by the hydrolysis of ceramide catalyzed by ceramidase (CDase) [ 4 ]. (clinsci.org)
• CerS are involved in the de novo synthesis pathway of ceramides. (wikipedia.org)
• All mammalian CerS, aside from CerS1, contain a Hox-like domain shared by transcription factors important in development, although the first 15 amino acids of this domain are missing in CerS, indicating that this domain likely does not function as a genuine transcription factor. (wikipedia.org)
• Inhibition of either of the enzymes serine palmitoyl transferase, CerS, and dihydroceramide desaturase within the de novo ceramide pathway reversed ceramide accumulation and cell death induced by R-MA treatment. (aacrjournals.org)
• (aacrjournals.org)
• We tested whether particular CerS isoforms promoted insulin resistance through the generation of more inhibitory ceramide species, thus representing potential targets for intervention. (garvan.org.au)
• Overexpression of CerS isoforms increased specific ceramides. (garvan.org.au)
• The modulation of ceramides through an alteration of CerS expression does not affect the action of insulin in the same way as ceramide generation by palmitate treatment. (garvan.org.au)
• Supporting the hypothesis that this translocation is mechanistically involved in the response to cisplatin, we showed that expression of SphK1, but not SphK2, abrogates both the increased cisplatin sensitivity in cells stably expressing LASS1/CerS and the translocation of the LASS1/CerS1. (illinois.edu)

CerS62

• CerS1 to CerS6 synthesize ceramides of varying chain length ( 2 ). (aacrjournals.org)
• Unexpectedly, the overexpression of CerS1 and CerS6 promoted insulin action, while no isoform had inhibitory effects. (garvan.org.au)

Sphingolipid6

• SM is definitely the many abundant sphingolipid, and therefore it is definitely an tremendous resource of ceramide era within the cell. (exposed-skin-care.net)
• Remarkably, serum sphingolipid analysis revealed significant differences in patterns of C 18 -ceramide elevation in patients with CR/PR/SD in comparison with patients with PD, indicating the reconstitution of tumor suppressor ceramide generation by GEM/DOX treatment. (aacrjournals.org)
• C 18 -ceramide is a bioactive sphingolipid with tumor suppressive functions. (aacrjournals.org)
• INTRODUCTION The bioactive sphingolipid ceramide is both a structural component of biological membranes and a signaling molecule that induces cell death and tumor suppression (= 3 independent experiments, ** 0.01). (antibodyassay.com)
• Ceramide (Cer) can be considered as a metabolic hub in the sphingolipid biosynthesis and catabolism (see Figure 1 ) ( Hannun and Obeid, 2008 ). (frontiersin.org)
• Castro BM, Prieto M, Silva LC (2014) Ceramide: a simple sphingolipid with unique biophysical properties. (springer.com)

CerS51

• Expression of LASS1/CerS1 increases the sensitivity to all the drugs tested, whereas LASS5/CerS5 only increases sensitivity to doxorubicin and vincristine. (illinois.edu)

Acyl chain1

• Ceramides are composed of a hydrophobic sphingoid backbone and a fatty acyl chain, linked to the backbone via an amino bond [ 1 ]. (clinsci.org)

Species5

• Accumulation of ceramide species C 16 , C 18 , C 24 , and C 24:1 in response to treatment with R-MA. (aacrjournals.org)
• When ceramide species C 18 was specifically induced in UM-SCC-22A cells (squamous cell carcinoma of hypopharynx) by overexpression of CerS1, cell growth was inhibited ( 6 ). (aacrjournals.org)
• CONCLUSIONS/INTERPRETATION: Palmitate may increase intracellular ceramide levels through sphingomyelin hydrolysis as well as de novo synthesis, but no particular species were implicated in the generation of insulin resistance. (garvan.org.au)
• TLR9-mediated dendritic cell activation uncovers mammalian ganglioside species with specific ceramide backbones that activate invariant natural kil. (nih.gov)
• 0.01, n = 10) in tumour compared to non-cancerous lung tissues, and there were no significant changes in the levels of other ceramide species (Supporting Information Fig S5). (nih.gov)

Dihydroceramide3

• The dihydroceramide is desaturated by dihydroceramide desaturase (DEGS) to ceramide ( 13 ). (aacrjournals.org)
• Dihydroceramide is normally desaturated by dihydroceramide desaturase [3 eventually, producing ceramide. (exposed-skin-care.net)
• In particular, reduction in the levels of sptlc1 and cerS1 mRNA in the brain tissues from manifest HD mice resulted in a significant decrease in the content of dihydroSphingosine, dihydroSphingosine-1-phospahte and dihydroCeramide [C18:as assessed by mass spectrometry. (frontiersin.org)

Synthetase1

• 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)

Isoforms2

• Conversely, certain isoforms promote insulin action, indicating the importance of ceramides in cell function. (garvan.org.au)
• In mammals, there are six TOK-001 isoforms of CerSs (CerS1-6), which present substrate choice for particular chain-length fatty acyl CoAs . (exposed-skin-care.net)

Sphingomyelin4

• Hydrolysis of the Sphingomyelin (SM) Path The second ceramide-generating path entails the hydrolysis of SM, which happens in the plasma walls, lysosomes, Emergency room, Golgi, and mitochondria [3, (exposed-skin-care.net)
• Acid sphingomyelinase (ASMase) catalyzes the hydrolysis of sphingomyelin to ceramide and mediates multiple responses involved in inflammatory and apoptotic signaling. (arvojournals.org)
• Sphingomyelinases are enzymes that catalyze the hydrolysis of sphingomyelin to ceramide, a central modulator of inflammatory cytokines and apoptotic signaling. (arvojournals.org)
• Recently, it is well-known that ceramide acts as an inducer of cell death, that sphingomyelin works as a regulator for microdomain function of the cell membrane, and that sphingosine-1-phosphate plays a role in cell survival/proliferation. (molcells.org)

Novo5

• Inhibition of enzymes in the de novo synthesis pathway before treatment with R-MA leads to disrupted ceramide synthesis. (aacrjournals.org)
• Our findings suggest that R-MA induces cell death in MCL via CB1-mediated up-regulation of the de novo ceramide synthesis pathway. (aacrjournals.org)
• For instance, C 16 ceramide, generated de novo , was accumulated during androgen ablation in the prostate cell line LNCaP ( 3 ). (aacrjournals.org)
• Several enzymes are involved in the de novo synthesis of ceramide, which starts with the precursors l -serine and palmitoyl-CoA. (aacrjournals.org)
• Para Novo Activity Path The activity path is normally the greatest characterized ceramide-generating path, which generally takes place in the endoplasmic reticulum (Er selvf?lgelig) and to a lesser level the mitochondrial membrane layer [3,(Amount 1). (exposed-skin-care.net)

Activity of ceramide1

• Once got into into the cytosol, the released sphingosine may re-enter the paths for the activity of ceramide and/or T1G and turns into as a base. (exposed-skin-care.net)

MRNA levels1

• 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)

Protein4

• G) LC3 protein great quantity in charge (Scr) and CerS1 little interfering RNA (siRNA)Ctreated cells incubated with 5 M SoSe for 3 hours. (antibodyassay.com)
• SoSe exposure elevated CerS1 mRNA and protein (fig. S1F) and in addition induced ceramide deposition in mitochondria (Fig. 1F). (antibodyassay.com)
• This protein is produced by a bicistronic gene which also produces the CERS1 protein from a non-overlapping reading frame. (genecards.org)
• By inducing cell stress and monitoring the various proteins that bind CerS1, we were able to show that PERMIT was the protein responsible for bringing CerS1 to the mitochondria. (prohealthlongevity.com)

Lipid5

• 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)

Enzymes2

• 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)

Mitochondria9

• content evaluations proof assisting a part of ceramide for apoptosis and discusses a part of mitochondria, including TOK-001 MOMP, Bcl-2 family members healthy proteins, ROS, and signaling paths, and crosstalk between these elements in the legislation of ceramide-induced apoptosis of RTCs. (exposed-skin-care.net)
• p17/PERMIT-mediated CerS1 import to mitochondria induces mitophagy. (antibodyassay.com)
• D) Left: Confocal images of UM-SCC-22A-Tet On cells induced for expression of CerS1WT stained for ceramide (green) and mitochondria (Tom20, red). (antibodyassay.com)
• E) TEMs show fusion of mitochondria, gold-labeled with ceramide antibodies, in UM-SCC-22A-Tet On cells Tet-induced for expression of CerS1WT (+Tet) compared to untreated (?Tet) control. (antibodyassay.com)
• F) Confocal pictures of UM-SCC-22A cells induced for appearance of CerS1WT by SoSe and stained for ceramide (green) and mitochondria (Tom20, reddish colored). (antibodyassay.com)
• Ceramide is a molecule that triggers mitophagy, the digestion of old mitochondria. (prohealthlongevity.com)
• So ceramide, a molecule that is produced in response to cell stress and damage, sends a signal to trigger digestion of the old mitochondria. (prohealthlongevity.com)
• In unravelling the secrets of mitochondrial maintenance, the team at MUSC hopes to one day develop a therapeutic that would mimic the signals the ceramides provide, allowing proper clearance of the damaged mitochondria. (prohealthlongevity.com)
• Our idea here is that, without changing PERMIT, we can generate ceramides in the mitochondria with targeted therapeutics. (prohealthlongevity.com)

Total ceramide1

• Time course of the accumulation of total ceramide in response to R-MA. (aacrjournals.org)

Gene2

• There is evidence the disease may be caused by homozygous mutation in the CERS1 gene on chromosome 19p12. (cdc.gov)
• An important paralog of this gene is CERS1 . (genecards.org)

Intracellular1

• Salvage Path A even more complicated legislation of intracellular ceramide amounts is definitely the repair path [2,3,(Number 1). (exposed-skin-care.net)

Accumulation5

• Here, we investigated the pathways of ceramide accumulation in the MCL cell line Rec-1 using the stable endocannabinoid analogue R (+)-methanandamide (R-MA). (aacrjournals.org)
• Ceramide accumulation is a widely described event in cancers after various treatments ( 1 ). (aacrjournals.org)
• In previous publications ( 7 - 9 ), we and others observed that induction of ceramide accumulation by cannabinoids leads to apoptosis in mantle cell lymphoma (MCL), glioma, and pancreatic cancer. (aacrjournals.org)
• In MCL, the accumulation of ceramide was mediated through the cannabinoid receptors type 1 (CB1) and type 2 (CB2), which are overexpressed on MCL cells, whereas control cells lacking the receptors remained unaffected. (aacrjournals.org)
• AIMS/HYPOTHESIS: An accumulation of ceramides has been implicated in the generation of insulin resistance in skeletal muscle upon an oversupply of fatty acid. (garvan.org.au)

CerSs2

• 3) Sphingosine can be recycled to generate ceramides by CerSs. (clinsci.org)
• The repair path re-utilizes sphingosine to form ceramide by an actions of CerSs [2,3, (exposed-skin-care.net)

Fatty2

• 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)

Genes2

• 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)

Apoptosis2

• C 16 -ceramide is described as one of the major ceramide subspecies, the levels of which are elevated during apoptosis induced by various agents ( 2 ). (aacrjournals.org)
• A controlling part TOK-001 between ceramide and H1G and the technique for avoiding ceramide-induced apoptosis by development elements are also talked about. (exposed-skin-care.net)

Ceramidase1

• The catabolism of ceramide in mammals occurs in lysosomes through the activity of ceramidase. (jle.com)

Modulation1

• Furthermore, this is the first study were the cytotoxic effect of a cannabinoid is enhanced by modulation of ceramide metabolism. (aacrjournals.org)

Mantle Cell Lym1

• Ceramide levels are elevated in mantle cell lymphoma (MCL) cells following treatment with cannabinoids. (aacrjournals.org)

Squamous1

• 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)

Phosphocholine2

• In the Golgi, ceramides transferred by CERT are predestined to synthesize sphingomyelins by the addition of phosphocholine head group or be phosphorylated to form ceramide-1-phosphate. (clinsci.org)
• This procedure is definitely mediated by either acidity sphingomyelinase (A-SMase) or natural sphingomyelinases (N-SMases), producing ceramide and phosphocholine [2,3,(Number 1). (exposed-skin-care.net)

Metabolic1

• Three metabolic pathways are involved in ceramide production ( Figure 1 ). (clinsci.org)

Proteins1

• Ultimately, ceramide prevents the cell from making the proteins necessary for migration. (musc.edu)