Sphingosine mediates the immediate negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian cardiac myocyte.
AuthorsOral H,Dorn GW 2nd,Mann DL
JournalThe Journal of biological chemistry
PubMed ID9030540
Tumor necrosis factor-alpha (TNF-alpha) signal transduction through ceramide. Dissociation of growth inhibitory effects of TNF-alpha from activation of nuclear factor-kappa B.
AuthorsDbaibo GS, Obeid LM, Hannun YA
JournalJ Biol Chem
PubMed ID8349660
Tumor necrosis factor-alpha (TNF-alpha) exerts pleiotropic biologic effects. Although TNF-alpha appears to activate a number of signal transduction pathways, the role of second messengers in mediating the different effects of TNF-alpha are not well defined. In this study, we investigated the role of ceramide as an intracellular mediator of TNF-alpha ... More
Sphingomyelinase and cell-permeable ceramide analogs stimulate cellular proliferation in quiescent Swiss 3T3 fibroblasts.
AuthorsOlivera A, Buckley NE, Spiegel S
JournalJ Biol Chem
PubMed ID1464623
Sphingomyelin or the products derived from its metabolism may constitute a signaling system involved in a variety of cellular processes. The activation of a plasma membrane neutral sphingomyelinase, which catalyzes the first step in sphingomyelin turnover, has been suggested to play an important role in cellular differentiation. We have studied ... More
Ceramide-mediated biology. Determination of structural and stereospecific requirements through the use of N-acyl-phenylaminoalcohol analogs.
AuthorsBielawska A, Linardic CM, Hannun YA
JournalJ Biol Chem
PubMed ID1526986
Ceramide is a postulated intracellular modulator of cell growth and differentiation (Okazaki, T., Bielawska, A., Bell, R.M., and Hannun, Y. A. (1990) J. Biol. Chem. 265, 15823-15831). In order to determine the structural and stereospecific requirements for ceramide effects on HL-60 cells, N-acyl-phenylaminoalcohol analogs were synthesized and evaluated for their ... More
Involvement of nuclear factor of activated T cells activation in UV response. Evidence from cell culture and transgenic mice.
AuthorsHuang C, Mattjus P, Ma WY, Rincon M, Chen NY, Brown RE, Dong Z
JournalJ Biol Chem
PubMed ID10734048
'Mammalian cells respond to UV radiation by signaling cascades leading to activation of transcription factors, such as activated protein 1, NFkappaB, and p53, a process known as the "UV response." Nuclear factor of activated T cells (NFAT) was first identified as an inducible nuclear factor in immune response and subsequently ... More
Neurotrophic factors prevent ceramide-induced apoptosis downstream of c-Jun N-terminal kinase activation in PC12 cells.
AuthorsHartfield PJ, Bilney AJ, Murray AW
JournalJ Neurochem
PubMed ID9648862
'Neurotrophic factors prevent apoptosis of PC12 cells in serum-free medium. The present study determines whether neurotrophic factors can prevent ceramide-induced apoptosis in PC12 cells and investigates the role that c-Jun N-terminal kinase (JNK) activation may play in this system. Ceramide-induced apoptosis was inhibited by nerve growth factor, basic fibroblast growth ... More
Sphingosine 1-phosphate induces platelet activation through an extracellular action and shares a platelet surface receptor with lysophosphatidic acid.
AuthorsYatomi Y, Yamamura S, Ruan F, Igarashi Y
JournalJ Biol Chem
PubMed ID9030602
'Sphingosine 1-phosphate (Sph-1-P) has been implicated as an intracellular second messenger in many studies. We investigated the metabolism of Sph-1-P and the mechanism by which Sph-1-P induces activation in enucleated and highly differentiated platelets. Platelets lack Sph-1-P lyase activity, possess persistently active sphingosine (Sph) kinase, and abundantly store Sph-1-P. Although ... More
Apoptogenic ganglioside GD3 directly induces the mitochondrial permeability transition.
AuthorsKristal BS, Brown AM
JournalJ Biol Chem
PubMed ID10438487
'Early events in apoptotic cascades initiated by ceramides or by activation of the surface receptor CD95 (Fas/APO-1) include the formation of ganglioside GD3. GD3 appears to be both necessary and sufficient to propagate this lipid-mediated apoptotic pathway. Later events common to many apoptotic pathways include induction of the mitochondrial permeability ... More
Regulatory role of ceramide in interleukin (IL)-1 beta-induced E-selectin expression in human umbilical vein endothelial cells. Ceramide enhances IL-1 beta action, but is not sufficient for E-selectin expression.
AuthorsMasamune A, Igarashi Y, Hakomori S
JournalJ Biol Chem
PubMed ID8621602
'Recent studies indicate that sphingolipids mediate several cellular processes. We assessed roles of sphingolipids in the regulation of E-selectin expression in human umbilical vein endothelial cells. All exogenously-added sphingolipids (sphingosine, C2-ceramide, sphingosine 1-phosphate, and N,N-dimethylsphingosine) failed to induce E-selectin expression by themselves. C2-ceramide at 5 micron enhanced interleukin-1 beta (IL-1 ... More
Fas/Apo-1 (CD95) receptor lacking the intracytoplasmic signaling domain protects tumor cells from Fas-mediated apoptosis.
AuthorsCascino I, Papoff G, De Maria R, Testi R, Ruberti G
JournalJ Immunol
PubMed ID8598453
'FAS/Apo-1 (CD95) is an apoptosis-signaling cell surface receptor belonging to the TNF receptor family. Tumor cells resistant to Fas-mediated apoptosis have been described, but to date, the mechanisms responsible for this resistance are not well understood. We found that a series of apoptosis-resistant clones from human HUT78 lymphoma cells express ... More
Dual role of ceramide in the control of apoptosis following IL-2 withdrawal.
AuthorsFlores I, Martinez-A C, Hannun YA, Mérida I
JournalJ Immunol
PubMed ID9531315
'Ceramide is largely known as a lipid second messenger with pleiotropic effects. Increases in ceramide levels have been related to the onset of apoptosis, terminal differentiation, or growth suppression. In this study, addition of exogenous C2-ceramide to CTLL-2 cells is found to block IL-2-induced cell cycle entry, as well as ... More
Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis.
AuthorsVerheij M, Bose R, Lin XH, Yao B, Jarvis WD, Grant S, Birrer MJ, Szabo E, Zon LI, Kyriakis JM, Haimovitz-Friedman A, Fuks Z, Kolesnick RN
JournalNature
PubMed ID8598911
'The induction of programmed cell death, or apoptosis, involves activation of a signalling system, many elements of which remain unknown. The sphingomyelin pathway, initiated by hydrolysis of the phospholipid sphingomyelin in the cell membrane to generate the second messenger ceramide, is thought to mediate apoptosis in response to tumour-necrosis factor ... More
Synthesis of Bcl-2 in response to anthracycline treatment may contribute to an apoptosis-resistant phenotype in leukemic cell lines.
AuthorsDurrieu F, Belaud-Rotureau MA, Lacombe F, Dumain P, Reiffers J, Boisseau MR, Bernard P, Belloc F
JournalCytometry
PubMed ID10554162
'BACKGROUND: Some forms of chemoresistance in leukemia may start from failure of tumour cells to successfully undergo apoptosis and Bcl-2 may play a role in this defect. Therefore, we evaluated the Bcl-2 content and synthesis in relation with the apoptotic potential in leukemic cell lines after anthracycline treatment. METHODS: U937, ... More
Selectivity of ceramide-mediated biology. Lack of activity of erythro-dihydroceramide.
AuthorsBielawska A, Crane HM, Liotta D, Obeid LM, Hannun YA
JournalJ Biol Chem
PubMed ID8253743
'Ceramide is emerging as a putative second messenger mediating effects of extracellular agents on cell growth and differentiation (Okazaki, T., Bielawska, A., Bell, R. M., and Hannun, Y. (1990) J. Biol. Chem. 265, 15822-15831) and programed cell death (Obeid, L. M., Linardic, C. M., Karolak, L. A., and Hannun, Y. ... More
Low temperatures and hypertonicity do not block cytokine-induced stimulation of the sphingomyelin pathway but inhibit nuclear factor-kappa B activation.
AuthorsAndrieu N, Salvayre R, Jaffrézou JP, Levade T
JournalJ Biol Chem
PubMed ID7592669
'In order to better understand the significance of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta)-receptor internalization in the sphingomyelin pathway signal transduction, we investigated receptor signaling under conditions in which receptor internalization is blocked. We demonstrate that human recombinant TNF-alpha and IL-1 beta both induced sphingomyelin and phosphatidylcholine ... More
Dissociation of endogenous cellular ceramide from NF-kappa B activation.
AuthorsBetts JC, Agranoff AB, Nabel GJ, Shayman JA
JournalJ Biol Chem
PubMed ID8132572
'The participation of cell ceramide in tumor necrosis factor (TNF)-alpha-stimulated NF-kappa B activation in Jurkat T cells and HL-60 cells was studied. TNF-alpha readily stimulated NF-kappa B activity in both cell lines as assayed by electrophoretic mobility shift assay and the use of a human immunodeficiency virus-chloramphenicol acetyltransferase reporter construct. ... More
N-acetylsphingosine (C2-ceramide) inhibited neutrophil superoxide formation and calcium influx.
AuthorsWong K, Li XB, Hunchuk N
JournalJ Biol Chem
PubMed ID7852386
'Ceramide, a product arising from sphingomyelinase activity, has been shown to act as an intracellular second messenger in effecting growth inhibition, cellular differentiation, and apoptosis. In the present study, the relative effects of cell-permeable ceramides, N-acetylsphingosine (C2-ceramide) and N-hexanoylsphingosine (C6-ceramide), on neutrophil responses were measured. When cells were activated with ... More
Requirement of AP-1 for ceramide-induced apoptosis in human leukemia HL-60 cells.
AuthorsSawai H, Okazaki T, Yamamoto H, Okano H, Takeda Y, Tashima M, Sawada H, Okuma M, Ishikura H, Umehara H
JournalJ Biol Chem
PubMed ID7592995
'Ceramide has emerged as a novel lipid mediator in cell proliferation, differentiation, and apoptosis. In this work, we demonstrate that the levels of c-jun mRNA, c-Jun protein, and DNA binding activity of a nuclear transcription factor AP-1 to 12-o-tetradecanoylphorbol 13-acetate responsive elements all increased following treatment with the cell-permeable ceramide, ... More
Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate.
AuthorsCuvillier O, Pirianov G, Kleuser B, Vanek PG, Coso OA, Gutkind S, Spiegel S
JournalNature
PubMed ID8657285
'Ceramide is an important regulatory participant of programmed cell death (apoptosis) induced by tumour-necrosis factor (TNF)-alpha and Fas ligand, members of the TNF superfamily. Conversely, sphingosine and sphingosine-1-phosphate, which are metabolites of ceramide, induce mitogenesis and have been implicated as second messengers in cellular proliferation induced by platelet-derived growth factor ... More
Binding of DNA to liposomes containing different derivatives of sphingosine.
AuthorsKõiv A, Kinnunen PK
JournalChem Phys Lipids
PubMed ID7923481
'Binding of DNA to dimyristoylphosphatidylcholine (DMPC) liposomes containing different sphingosine derivatives was investigated. DNA labelled with adriamycin was used as a fluorescence quencher and its membrane association was observed by resonance energy transfer from liposomes incorporating a pyrene-derivatized lipid bisPDPC as a donor and containing 19 mol% of sphingosine, dihydro-, ... More
Inhibition of Akt kinase by cell-permeable ceramide and its implications for ceramide-induced apoptosis.
Authors Zhou H; Summers S A; Birnbaum M J; Pittman R N;
JournalJ Biol Chem
PubMed ID9632728
'Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. However, mechanisms responsible for ceramide-induced apoptosis remain unclear. We investigated the possibility that ceramide may decrease antiapoptotic signaling in cells by inhibiting Akt kinase activity. Our data show that C2-ceramide induces apoptosis in HMN1 ... More
Sphingosine: a mediator of acute renal tubular injury and subsequent cytoresistance.
AuthorsIwata M, Herrington J, Zager RA
JournalProc Natl Acad Sci U S A
PubMed ID7568054
'The goal of this study was to determine whether sphingosine and ceramide, second messengers derived from sphingolipid breakdown, alter kidney proximal tubular cell viability and their adaptive responses to further damage. Adult human kidney proximal tubular (HK-2) cells were cultured for 0-20 hr in the presence or absence of sphingosine, ... More
Protein kinase CbetaII activation by 1-beta-D-arabinofuranosylcytosine is antagonistic to stimulation of apoptosis and Bcl-2alpha down-regulation.
AuthorsWhitman SP, Civoli F, Daniel LW
JournalJ Biol Chem
PubMed ID9295281
'1-beta-D-Arabinofuranosylcytosine (ara-C) stimulates the formation of both diglyceride and ceramide in the acute myelogenous leukemia cell line HL-60 (Strum, J. C., Small, G. W., Pauig, S. B., and Daniel, L. W. (1994) J. Biol. Chem 269, 15493-15497). ara-C also causes apoptosis in HL-60 cells which can be mimicked by exogenous ... More
Tumor necrosis factor-alpha autoregulates interleukin-6 synthesis via activation of protein kinase C. Function of sphingosine 1-phosphate and phosphatidylcholine-specific phospholipase C.
AuthorsKozawa O, Suzuki A, Kaida T, Tokuda H, Uematsu T
JournalJ Biol Chem
PubMed ID9312119
'We investigated the mechanism of interleukin-6 (IL-6) synthesis induced by tumor necrosis factor-alpha (TNF) in osteoblast-like MC3T3-E1 cells. TNF stimulated the synthesis of IL-6 dose dependently in the range between 1 and 30 ng/ml. Staurosporine and calphostin C, inhibitors of protein kinase C (PKC), significantly enhanced the TNF-induced synthesis of ... More
Ceramide-induced translocation of protein kinase C-delta and -epsilon to the cytosol. Implications in apoptosis.
AuthorsSawai H, Okazaki T, Takeda Y, Tashima M, Sawada H, Okuma M, Kishi S, Umehara H, Domae N
JournalJ Biol Chem
PubMed ID8999958
'Ceramide is now recognized as an intracellular lipid signal mediator, which induces various kinds of cell functions including apoptosis. Ceramide-induced apoptosis was reported to be blocked by 12-O-tetradecanoylphorbol 13-acetate, a protein kinase C (PKC) activator, but its mechanism remained unclear. Therefore, we investigated whether ceramide has any effects on PKC ... More
Ceramide formation leads to caspase-3 activation during hypoxic PC12 cell death. Inhibitory effects of Bcl-2 on ceramide formation and caspase-3 activation.
AuthorsYoshimura S, Banno Y, Nakashima S, Takenaka K, Sakai H, Nishimura Y, Sakai N, Shimizu S, Eguchi Y, Tsujimoto Y, Nozawa Y
JournalJ Biol Chem
PubMed ID9506997
'PC12 cells undergo apoptosis as well as necrosis following exposure to hypoxia. Following a 6-h hypoxic treatment, a time-dependent increase in intracellular ceramide level was observed with a concurrent decrease in sphingomyelin. It was also shown that the hypoxia-induced ceramide accumulation resulted from activation of neutral magnesium-dependent sphingomyelinase. Comparative kinetic ... More
Sphingosine 1-phosphate stimulates tyrosine phosphorylation of Crk.
AuthorsBlakesley VA, Beitner-Johnson D, Van Brocklyn JR, Rani S, Shen-Orr Z, Stannard BS, Spiegel S, LeRoith D
JournalJ Biol Chem
PubMed ID9195921
'The proto-oncogene molecule c-Crk plays a role in growth factor-induced activation of Ras. Sphingosine 1-phosphate (SPP), a metabolite of cellular sphingolipids, has previously been shown to play a role in growth factor receptor signaling (Olivera, A., and Spiegel, S. (1993) Nature 365, 557-560). SPP was found to strongly induce tyrosine ... More
Potential role for ceramide in mitogen-activated protein kinase activation and proliferation of vascular smooth muscle cells induced by oxidized low density lipoprotein.
AuthorsAugé N, Escargueil-Blanc I, Lajoie-Mazenc I, Suc I, Andrieu-Abadie N, Pieraggi MT, Chatelut M, Thiers JC, Jaffrézou JP, Laurent G, Levade T, Nègre-Salvayre A, Salvayre R
JournalJ Biol Chem
PubMed ID9582320
'Proliferation of vascular smooth muscle cells (SMC) is a hallmark in the pathogenesis of atherosclerotic lesions. Mildly oxidized low density lipoproteins (UV-oxLDL), which are mitogenic to cultured AG-08133A SMC, activate the sphingomyelin (SM)-ceramide pathway. We report here the following. (i) UV-oxLDL elicited a biphasic and sustained activation of MBP kinase ... More
A mediator role of ceramide in the regulation of neuroblastoma Neuro2a cell differentiation.
AuthorsRiboni L, Prinetti A, Bassi R, Caminiti A, Tettamanti G
JournalJ Biol Chem
PubMed ID7592930
'Current studies indicate that ceramide is involved in the regulation of important cell functions, namely cell growth, differentiation, and apoptosis. In the present study, the possible role of ceramide in the differentiation of neuroblastoma Neuro2a cells was investigated. The following results were obtained. (a) Ceramide content of Neuro2a cells, induced ... More
Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75.
AuthorsCasaccia-Bonnefil P, Carter BD, Dobrowsky RT, Chao MV
JournalNature
PubMed ID8878481
'Members of the nerve growth factor (NGF) family promote the survival of neurons during development. NGF specifically activates the receptor trkA, initiating a signal transduction cascade which ultimately blocks cell death. Here we show that NGF can have the opposite effect, inducing the death of mature oligodendrocytes cultured from postnatal ... More
Ceramide activates the stress-activated protein kinases.
AuthorsWestwick JK, Bielawska AE, Dbaibo G, Hannun YA, Brenner DA
JournalJ Biol Chem
PubMed ID7559390
'Tumor necrosis factor alpha (TNF alpha) activates the stress-activated protein kinases (SAPKs, also known as Jun nuclear kinases or JNKs) resulting in the stimulation of AP-1-dependent gene transcription and induces the translocation of NF kappa B to the nucleus resulting in the stimulation of NF kappa B-dependent gene transcription. A ... More
Induction of endocytic vesicles by exogenous C(6)-ceramide.
AuthorsLi R, Blanchette-Mackie EJ, Ladisch S
JournalJ Biol Chem
PubMed ID10409665
'Ceramide is a newly discovered second messenger that has been shown to cause cell growth arrest and apoptosis. Here, we present evidence that exogenously added C(6)-ceramide induces enlargement of late endosomes and lysosomes. 10 microM C(6)-ceramide caused the formation of numerous vesicles of varying sizes (2-10 micrometers) in fibroblasts (3T3-L1 ... More
Modified low density lipoprotein delivers substrate for ceramide formation and stimulates the sphingomyelin-ceramide pathway in human macrophages.
AuthorsKinscherf R, Claus R, Deigner HP, Nauen O, Gehrke C, Hermetter A, Russwurm S, Daniel V, Hack V, Metz J
JournalFEBS Lett
PubMed ID9094423
'Exposure of human blood monocytes derived macrophages to modified (oxidized or acetylated) LDL induced a approximately 40% elevation (60 pmol/10(6) cells) of the endogenous level of the sphingolipid ceramide. A rise of both neutral and acidic SMase activity was found after treatment with oxidized LDL (250 and 80%), while addition ... More
Ceramide reverses brefeldin A (BFA) resistance in BFA-resistant cell lines.
AuthorsOda T, Chen CH, Wu HC
JournalJ Biol Chem
PubMed ID7876158
'We have found that C6 ceramide, a cell-permeable ceramide analog, partially restored the brefeldin A (BFA) sensitivity in a BFA-resistant mutant of Vero cells (BER-40) and in the naturally BFA-resistant Madin-Darby canine kidney (MDCK) cells. Incubation of BER-40 and MDCK cells with low concentrations of C6 ceramide resulted in (i) ... More
Regulation of cytochrome P450 2C11 (CYP2C11) gene expression by interleukin-1, sphingomyelin hydrolysis, and ceramides in rat hepatocytes.
AuthorsChen J, Nikolova-Karakashian M, Merrill AH, Morgan ET
JournalJ Biol Chem
PubMed ID7559661
'Interleukin-1 triggers the down-regulation of several hepatic cytochrome P450 gene products, but the cellular signaling pathways involved are not known. We have examined the role of sphingomyelin hydrolysis to ceramide in the suppression of CYP2C11, a major constitutive form of cytochrome P450, by interleukin-1. Treatment of rat hepatocytes cultured on ... More
Ceramide regulates oxidant release in adherent human neutrophils.
AuthorsNakamura T, Abe A, Balazovich KJ, Wu D, Suchard SJ, Boxer LA, Shayman JA
JournalJ Biol Chem
PubMed ID8034585
'We investigated the role of sphingolipids in regulating oxidant release in adherent human neutrophils. Stimulation of adherent neutrophils with formyl-Met-Leu-Phe (fMLP) resulted in the accumulation of ceramide at a time when H2O2 release is terminated. H2O2 release in fMLP-stimulated neutrophils was suppressed in a concentration-dependent manner by the exogenous addition ... More
Changes in the activity and mRNA levels of phospholipase D during ceramide-induced apoptosis in rat C6 glial cells.
AuthorsYoshimura S, Sakai H, Ohguchi K, Nakashima S, Banno Y, Nishimura Y, Sakai N, Nozawa Y
JournalJ Neurochem
PubMed ID9231731
'N-Acetylsphingosine (C2-ceramide), a membrane-permeable analogue, induced apoptosis in C6 glial cells. Phase-contrast micrographs showed that the round cells appeared 3 h after exposure to 25 microM C2-ceramide and the number of floating cells increased time-dependently. Staining with Hoechst 33258 dye showed condensed or fragmented nuclei in round cells at 12 ... More
Sphingomyelinase stimulates 2-deoxyglucose uptake by skeletal muscle.
AuthorsTurinsky J, Nagel GW, Elmendorf JS, Damrau-Abney A, Smith TR
JournalBiochem J
PubMed ID8546686
'The effects of sphingomyelinase, phosphorylcholine, N-acetylsphingosine (C2-ceramide), N-hexanoylsphingosine (C6-ceramide) and sphingosine on basal and insulin-stimulated cellular accumulation of 2-deoxy-D-glucose in rat soleus muscles were investigated. Preincubation of muscles with sphingomyelinase (100 or 200 m-units/ml) for 1 or 2 h augmented basal 2-deoxyglucose uptake by 29-91%, and that at 0.1 and ... More
Sphingosylphosphocholine reduces the calcium ion requirement for activating tissue transglutaminase.
AuthorsLai TS, Bielawska A, Peoples KA, Hannun YA, Greenberg CS
JournalJ Biol Chem
PubMed ID9195933
'Tissue transglutaminase (tTG) catalyzes a Ca2+-dependent transglutaminase reaction resulting in the formation of gamma-glutamyl-epsilon-lysine bonds and is activated during apoptosis to catalyze the formation of apoptotic body. We investigate whether lipids that are membrane components and involved in cell signaling could modify the Ca2+-dependent activation of tTG. We found that ... More
Synergy between tumor necrosis factor alpha and interleukin 1beta in inducing transcriptional down-regulation of muscarinic M2 receptor gene expression. Involvement of protein kinase A and ceramide pathways.
'Stimulation of HEL 299 cells with tumor necrosis factor alpha (TNF-alpha) or interleukin 1beta (IL-1beta) had no effect on M2 muscarinic receptor expression. However, the combination of these two cytokines markedly down-regulated muscarinic M2 receptor protein and mRNA expression and uncoupled M2 receptors from adenylyl cyclase. There was no effect ... More
CD95/Fas-induced ceramide formation proceeds with slow kinetics and is not blocked by caspase-3/CPP32 inhibition.
AuthorsTepper AD, Cock JG, de Vries E, Borst J, van Blitterswijk WJ
JournalJ Biol Chem
PubMed ID9305886
'The current confusion regarding the relevance of endogenous ceramide in mediating CD95/Fas-induced apoptosis is based mainly on (i) discrepancies in kinetics of the ceramide response between different studies using the same apoptotic stimulus and (ii) the observation that late ceramide formation (hours) often parallels apoptosis onset. We investigated CD95-induced ceramide ... More
Direct inhibition of mitochondrial respiratory chain complex III by cell-permeable ceramide.
AuthorsGudz TI, Tserng KY, Hoppel CL
JournalJ Biol Chem
PubMed ID9305864
'Ceramide is a lipid second messenger that mediates the effects of tumor necrosis factor alpha and other agents on cell growth and differentiation. Ceramide is believed to act via activation of protein phosphatase, proline-directed protein kinase, or protein kinase C. Tumor necrosis factor alpha-induced common pathway of apoptosis is associated ... More
Inhibition of acyl-CoA:cholesterol acyltransferase in Chinese hamster ovary (CHO) cells by short-chain ceramide and dihydroceramide.
AuthorsRidgway ND
JournalBiochim Biophys Acta
PubMed ID7742354
'The biological activity of ceramide, an intermediate in the synthesis and catabolism of sphingolipids, has been shown to be mimicked by short-chain N-acyl analogues. A potential role for ceramide in modulating cholesterol esterification was investigated using a series of short-chain ceramides and dihydroceramides. Acyl-CoA:cholesterol acyltransferase (ACAT) in CHO cells was ... More
Homeostasis of cell-surface glycosphingolipid content in B16 melanoma cells. Evidence revealed by an endoglycoceramidase.
AuthorsIto M, Komori H
JournalJ Biol Chem
PubMed ID8647878
'This paper describes the homeostasis of glycosphingolipid (GSL) on the cell surface as revealed for the first time by an application of endoglycoceramidase (EGCase) capable of hydrolyzing the linkage between the oligosaccharide and the ceramide of various GSLs. When cell-surface GSLs of B16 melanoma cells were hydrolyzed by the action ... More
Purification, characterization, and biosynthesis of human acid ceramidase.
'Acid ceramidase (N-acylsphingosine deacylase, EC 3.5.1.23) is the lysosomal enzyme catalyzing the hydrolysis of ceramide to sphingosine and free fatty acid. Its inherited deficiency causes ceramide accumulation in Farber''s disease. The enzyme was purified to apparent homogeneity from human urine by sequential chromatography on octyl-Sepharose, concanavalin A-Sepharose, blue-Sepharose, and DEAE-cellulose. ... More
Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate.
AuthorsLee MJ, Thangada S, Claffey KP, Ancellin N, Liu CH, Kluk M, Volpi M, Sha'afi RI, Hla T
JournalCell
PubMed ID10555146
Vascular endothelial cells undergo morphogenesis into capillary networks in response to angiogenic factors. We show here that sphingosine-1-phosphate (SPP), a platelet-derived bioactive lipid, activates the EDG-1 and -3 subtypes of G protein-coupled receptors on endothelial cells to regulate angiogenesis. SPP induces the Gi/mitogen-activated protein kinase/cell survival pathway and the small ... More
Proteolysis of fodrin (non-erythroid spectrin) during apoptosis.
AuthorsMartin SJ, O'Brien GA, Nishioka WK, McGahon AJ, Mahboubi A, Saido TC, Green DR
JournalJ Biol Chem
PubMed ID7534762
Several recent studies have implicated proteases as important triggers of apoptosis. Thus far, substrates that are cleaved during apoptosis have been elusive. In this report we demonstrate that cleavage of alpha-fodrin (non-erythroid spectrin) accompanies apoptosis, induced by activation via the CD3/T cell receptor complex in a murine T cell hybridoma, ... More
Programmed cell death induced by ceramide.
AuthorsObeid LM, Linardic CM, Karolak LA, Hannun YA
JournalScience
PubMed ID8456305
Sphingomyelin hydrolysis and ceramide generation have been implicated in a signal transduction pathway that mediates the effects of tumor necrosis factor-alpha (TNF-alpha) and other agents on cell growth and differentiation. In many leukemic cells, TNF-alpha causes DNA fragmentation, which leads to programmed cell death (apoptosis). C2-ceramide (0.6 to 5 microM), ... More
Sphingosine-induced inhibition of capacitative calcium influx in CFPAC-1 cells.
AuthorsOrlati S, Cavazzoni M, Rugolo M
JournalCell Calcium
PubMed ID8955554
Sphingosine (10 microM) induced mobilization of intracellular Ca2+ stores in the pancreatic duct adenocarcinoma cell line CFPAC-1. The effect was specific for sphingosine, since the sphingosine analog C2-ceramide had no effect. Sphingosine did not cause Ca2+ entry from extracellular medium, as also shown by following Mn2+ quenching of Fura-2 fluorescence. ... More
Brain-derived neurotrophic factor binding to the p75 neurotrophin receptor reduces TrkA signaling while increasing serine phosphorylation in the TrkA intracellular domain.
AuthorsMacPhee IJ, Barker PA
JournalJ Biol Chem
PubMed ID9295291
We have examined whether the low affinity neurotrophin receptor p75NTR modulates TrkA function by intracellular signaling. Using ligands that selectively bind p75NTR or TrkA, we found that a p75NTR-derived signal reduces TrkA activation. Short term treatment of PC12 cells with ceramide analogues also resulted in reduced NGF-stimulated TrkA activation, suggesting ... More
Inflammatory activation of arachidonic acid signaling in murine P388D1 macrophages via sphingomyelin synthesis.
AuthorsBalsinde J, Balboa MA, Dennis EA
JournalJ Biol Chem
PubMed ID9252342
Ceramide has emerged as an important lipid messenger for many cellular processes triggered via surface receptors. In the present study, inflammatory activation of P388D1 macrophages with bacterial lipopolysaccharide (LPS) and platelet-activating factor (PAF) stimulated a transient accumulation of ceramide. Moreover, cell-permeable ceramide mimicked LPS/PAF in triggering arachidonate mobilization in these ... More
Keratinocyte differentiation is induced by cell-permeant ceramides and its proliferation is promoted by sphingosine.
AuthorsWakita H, Tokura Y, Yagi H, Nishimura K, Furukawa F, Takigawa M
JournalArch Dermatol Res
PubMed ID7979551
Ceramide and sphingosine have been suggested to be intracellular modulators of cell growth and differentiation. The effects of these sphingolipids on the growth and differentiation of keratinocytes were examined using cultured human keratinocytes (the squamous cell carcinoma cell line, DJM-1). The synthetic short-chain cell-permeant analogues of ceramides, N-acetylsphingosine, N-hexanoylsphingosine and ... More
Mitochondrial free radical signal in ceramide-dependent apoptosis: a putative mechanism for neuronal death in Parkinson's disease.
AuthorsFrance-Lanord V, Brugg B, Michel PP, Agid Y, Ruberg M
JournalJ Neurochem
PubMed ID9326290
Activation of the apoptogenic sphingomyelin-dependent signaling pathway in neuronally differentiated PC12 cells with cell-permeant C2-ceramide resulted in a transient and short-lived emission of reactive oxygen species that was maximal 6 h after the beginning of treatment, followed immediately by nuclear translocation of the transcription factor nuclear factor kappaB. The production ... More
Direct evidence for an important role of sphingomyelinase in ultraviolet-induced activation of c-Jun N-terminal kinase.
AuthorsHuang C, Ma W, Ding M, Bowden GT, Dong Z
JournalJ Biol Chem
PubMed ID9346918
Sphingomyelinase (SMase) and its product ceramide have recently attracted a great deal of attention because of their possible role in the signal transduction pathway. However, the role of sphingomyelinase in UV-induced c-June N-terminal kinase (JNK) activation is still unclear. Thus, we investigated this issue directly using a genetic SMase-deficient (2 ... More
Evidence that ceramide selectively inhibits protein kinase C-alpha translocation and modulates bradykinin activation of phospholipase D.
AuthorsJones MJ, Murray AW
JournalJ Biol Chem
PubMed ID7890607
Sphingomyelinase (SMase) treatment (0.1 unit/ml for up to 30 min) of mouse epidermal (HEL-37) or human skin fibroblast (SF 3155) cells preincubated with [3H]serine to label the sphingomyelin pool caused the accumulation of labeled ceramide but not sphingosine or ceramide 1-phosphate. Incubation of HEL-37 cells with dioctanoylglycerol (diC8) or SF ... More
Sphingomyelinase and ceramide suppress insulin-induced tyrosine phosphorylation of the insulin receptor substrate-1.
AuthorsKanety H, Hemi R, Papa MZ, Karasik A
JournalJ Biol Chem
PubMed ID8626623
The sphingomyelin pathway is a newly described signal transduction pathway mediating the action of several cytokines including tumor necrosis factor-alpha (TNF). TNF was recently shown to interfere with insulin-induced tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1). In this work we examined the possible effect of direct activation of the ... More
Endothelial cell death induced by tumor necrosis factor-alpha is inhibited by the Bcl-2 family member, A1.
AuthorsKarsan A, Yee E, Harlan JM
JournalJ Biol Chem
PubMed ID8910286
Endothelial cells play a central role in the inflammatory process. Tumor necrosis factor-alpha (TNF) is a multifunctional cytokine which elicits many of the inflammatory responses of endothelial cells. While TNF directly causes apoptosis of tumor cells and virally infected cells, normal cells are generally resistant. However, most resistant cells, including ... More
Flow cytometric analysis of mitochondrial activity in situ: application to acetylceramide-induced mitochondrial swelling and apoptosis.
AuthorsMacouillard-Poulletier de Gann Belaud-Rotureau MA, Voisin P, Leducq N, Belloc F, Canioni P, Diolez P
JournalCytometry
PubMed ID9822344
Changes in mitochondrial matrix volume were studied both on isolated mitochondria and in situ on CHME 5 human microglia and monoblastoid U 937 cells using multiparametric flow cytometric analysis. The use of specific effectors of mitochondrial activity (oligomycin and KCN) allowed the demonstration, on whole cells, of a strict correlation ... More
Requirement of calmodulin binding by HIV-1 gp160 for enhanced FAS-mediated apoptosis.
AuthorsMicoli KJ, Pan G, Wu Y, Williams JP, Cook WJ, McDonald JM
JournalJ Biol Chem
PubMed ID10625668
Accelerated apoptosis is one mechanism proposed for the loss of CD4+ T-lymphocytes in human immunodeficiency virus type 1 (HIV-1) infection. The HIV-1 envelope glycoprotein, gp160, contains two C-terminal calmodulin-binding domains. Expression of gp160 in Jurkat T-cells results in increased sensitivity to FAS- and ceramide-mediated apoptosis. The pro-apoptotic effect of gp160 ... More
Cell-permeable ceramides prevent the activation of phospholipase D by ADP-ribosylation factor and RhoA.
AuthorsAbousalham A, Liossis C, O'Brien L, Brindley DN
JournalJ Biol Chem
PubMed ID8995404
The mechanism of inhibition of phospholipase D (PLD) by ceramides was determined using granulocytes differentiated from human promyelocytic leukemic (HL-60) cells. In a cell-free system, hydrolysis of phosphatidylcholine by membrane-bound PLD depended upon phosphatidylinositol 4,5-bisphosphate, guanosine 5'-3-O-(thio)triphosphate) (GTPgammaS), and cytosolic factors including ADP-ribosylating factor (ARF) and RhoA. C2-(N-acetyl-), C8- (N-octanoyl-), ... More
The p75(NTR)-induced apoptotic program develops through a ceramide-caspase pathway negatively regulated by nitric oxide.
AuthorsLièvremont JP, Sciorati C, Morandi E, Paolucci C, Bunone G, Della Valle G, Meldolesi J, Clementi E
JournalJ Biol Chem
PubMed ID10336437
SK-N-BE neuroblastoma cell clones transfected with p75(NTR) and lacking Trk neurotrophin receptors, previously reported to undergo extensive spontaneous apoptosis and to be protected by nerve growth factor (NGF) (Bunone, G., Mariotti, A., Compagni, A., Morandi, E., and Della Valle, G. (1997) Oncogene 14, 1463-1470), are shown to exhibit (i) increased ... More
Ceramide triggers meiotic cell cycle progression in Xenopus oocytes. A potential mediator of progesterone-induced maturation.
AuthorsStrum JC, Swenson KI, Turner JE, Bell RM
JournalJ Biol Chem
PubMed ID7768956
The role of sphingomyelin-derived second messengers in progesterone-induced reinitiation of the meiotic cell cycle of Xenopus laevis oocytes was investigated. A brief treatment of defolliculated oocytes with sphingomyelinase (Staphylococcus aureus) was sufficient to induce maturation as measured by H1 kinase activity and germinal vesicle breakdown (GVBD). Pretreatment with cycloheximide inhibited ... More
Ceramide as a modulator of endocytosis.
AuthorsChen CS, Rosenwald AG, Pagano RE
JournalJ Biol Chem
PubMed ID7768929
The effects of ceramide analogs on the uptake of markers for fluid-phase (horseradish peroxidase, HRP) and receptor-mediated (low density lipoprotein, LDL) endocytosis were studied in Chinese hamster fibroblasts. N-Hexanoyl-D-erythro-sphingosine (C6-Cer) decreased the uptake of HRP in a dose-dependent manner. Internalization was inhibited > 40% with 25 microM C6-Cer, relative to ... More
Sphingomyelinase and ceramide activate mitogen-activated protein kinase in myeloid HL-60 cells.
AuthorsRaines MA, Kolesnick RN, Golde DW
JournalJ Biol Chem
PubMed ID7686898
Mechanisms involved in tumor necrosis factor (TNF)-alpha signal transduction are incompletely understood. In some circumstances, TNF may use a signal transduction pathway involving hydrolysis of sphingomyelin to ceramide and stimulation of a ceramide-activated protein kinase. In HL-60 cells, TNF rapidly activates this pathway and induces monocytic differentiation. Here, we demonstrate ... More
Nitric oxide inhibits the tumor necrosis factor alpha -regulated endocytosis of human dendritic cells in a cyclic GMP-dependent way.
AuthorsPaolucci C, Rovere P, De Nadai C, Manfredi AA, Clementi E
JournalJ Biol Chem
PubMed ID10777484
Tumor necrosis factor-alpha (TNFalpha)-induced maturation of dendritic cells (DC), with down-regulation of their endocytic ability, has been reported to be mediated by the accumulation of the lipid messenger ceramide. We have now studied the effects and mechanisms of action of NO on endocytosis, investigated with fluorescein isothiocyanate-labeled dextran using human ... More
Dual actions of sphingosine-1-phosphate: extracellular through the Gi-coupled receptor Edg-1 and intracellular to regulate proliferation and survival.
AuthorsVan Brocklyn JR, Lee MJ, Menzeleev R, Olivera A, Edsall L, Cuvillier O, Thomas DM, Coopman PJ, Thangada S, Liu CH, Hla T, Spiegel S
JournalJ Cell Biol
PubMed ID9660876
Sphingosine-1-phosphate (SPP), a bioactive lipid, acts both intracellularly and extracellularly to cause pleiotropic biological responses. Recently, we identified SPP as a ligand for the G protein-coupled receptor Edg-1 (Lee, M.-J., J.R. Van Brocklyn, S. Thangada, C.H. Liu, A.R. Hand, R. Menzeleev, S. Spiegel, and T. Hla. 1998. Science. 279:1552-1555). Edg-1 ... More
Differential modulation of apoptosis sensitivity in CD95 type I and type II cells.
AuthorsScaffidi C, Schmitz I, Zha J, Korsmeyer SJ, Krammer PH, Peter ME
JournalJ Biol Chem
PubMed ID10428830
We have recently identified two different pathways of CD95-mediated apoptosis (Scaffidi, C., Fulda, S., Srinivasan, A., Feng, L., Friesen, C., Tomaselli, K. J., Debatin, K.-M., Krammer, P. H., and Peter, M. E. (1998) EMBO J. 17, 1675-1687). CD95-mediated apoptosis in type I cells is initiated by large amounts of active ... More
Identification of a Saccharomyces gene, LCB3, necessary for incorporation of exogenous long chain bases into sphingolipids.
AuthorsQie L, Nagiec MM, Baltisberger JA, Lester RL, Dickson RC
JournalJ Biol Chem
PubMed ID9195906
To identify genes necessary for sphingolipid synthesis in Saccharomyces cerevisiae we developed a procedure to enrich for mutants unable to incorporate exogenous long chain base into sphingolipids. We show here that a mutant strain, AG84-3, isolated by using the enrichment procedure, makes sphingolipids from endogenously synthesized but not from exogenously ... More
Interaction of ceramides, sphingosine, and sphingosine 1-phosphate in regulating DNA synthesis and phospholipase D activity.
AuthorsGómez-Muñoz A, Waggoner DW, O'Brien L, Brindley DN
JournalJ Biol Chem
PubMed ID7592842
C2- and C6-ceramides (N-acetylsphingosine and N-hexanoylsphingosine, respectively) abolished the stimulation of DNA synthesis by sphingosine 1-phosphate in rat fibroblasts. This inhibition by ceramide was partially prevented by insulin. C2-ceramide did not alter the stimulation of DNA synthesis by insulin and decreased the sphingosine-induced stimulation by only 16%. The ceramides did ... More
Regulation of phospholipase D by sphingosine involves both protein kinase C-dependent and -independent mechanisms in NIH 3T3 fibroblasts.
AuthorsKiss Z, Deli E
JournalBiochem J
PubMed ID1472000
Previously, the protein kinase C (PKC) inhibitor sphingosine was found to stimulate phospholipase D (PLD)-mediated hydrolysis of both phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (PtdCho) in NIH 3T3 fibroblasts [Kiss & Anderson (1990) J. Biol. Chem. 265, 7345-7350]. Here we examined the possible relationship between the opposite effects of sphingosine on PKC-mediated ... More
Programmed cell death in cortical chick embryo astrocytes is associated with activation of protein kinase PK60 and ceramide formation.
AuthorsMangoura D, Dawson G
JournalJ Neurochem
PubMed ID9422355
Embryonic astrocytes respond readily to serine/threonine kinase regulation in terms of cytoskeleton assembly, mitotic activity, and cell fate. We now present evidence that these responses include apoptosis. Staurosporine induced apoptosis in astrocyte cultures derived from chick embryo cerebral hemispheres, as assayed both by immunocytochemical detection of new 3-hydroxy DNA ends ... More
Modulation by sphingolipids of calcium signals evoked by epidermal growth factor.
AuthorsHudson PL, Pedersen WA, Saltsman WS, Liscovitch M, MacLaughlin DT, Donahoe PK, Blusztajn JK
JournalJ Biol Chem
PubMed ID8063833
Receptor-activated breakdown of complex sphingolipids has been proposed as a mechanism for generating sphingoid base-containing putative second messenger molecules whose actions may modulate responses to extracellular signals. In human epidermoid carcinoma A431 cells, sphingosine (1-10 microM) by itself had no effect on intracellular free calcium concentrations ([Ca2+]i), yet within seconds, ... More
(1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol as an inhibitor of ceramidase.
AuthorsBielawska A, Greenberg MS, Perry D, Jayadev S, Shayman JA, McKay C, Hannun YA
JournalJ Biol Chem
PubMed ID8647877
In this study, we have examined the cellular and biochemical activities of the ceramide analog (1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol (D-erythro-MAPP). Addition of 5 microM D-e-MAPP to HL-60 human promyelocytic leukemia cells resulted in a concentration- and time-dependent growth suppression accompanied by an arrest in the G0/G1 phase of the cell cycle; thus mimicking ... More
A novel enzyme that catalyzes the esterification of N-acetylsphingosine. Metabolism of C2-ceramides.
AuthorsAbe A, Shayman JA, Radin NS
JournalJ Biol Chem
PubMed ID8662981
A unique transacylase that catalyzes esterification of a short chain ceramide, N-acetylsphingosine, was found in Madin-Darby canine kidney cell and mouse tissue homogenates. It esterified the hydroxyl group at the carbon-1 position of the ceramide. The enzyme has a pH optimum of 4.2 and a Km of 9.4 microM for ... More
Ceramide interaction with the respiratory chain of heart mitochondria.
AuthorsDi Paola M, Cocco T, Lorusso M
JournalBiochemistry
PubMed ID10828984
A study is presented on the interaction of ceramide with the respiratory chain of rat heart mitochondria, and a comparison is made between the effects elicited by short- and long-chain ceramides. N-Acetylsphingosine (C(2)-ceramide) and N-palmitoylsphingosine (C(16)-ceramide) inhibited to the same extent the pyruvate+malate-dependent oxygen consumption. Succinate-supported respiration was also inhibited ... More
Interleukin-1 activates p54 mitogen-activated protein (MAP) kinase/stress-activated protein kinase by a pathway that is independent of p21ras, Raf-1, and MAP kinase kinase.
AuthorsBird TA, Kyriakis JM, Tyshler L, Gayle M, Milne A, Virca GD
JournalJ Biol Chem
PubMed ID7527398
In KB epidermoid cells, we previously showed that interleukin-1 alpha (IL-1) and various mitogens activate the mitogen-activated protein (MAP) kinases ERK1 and ERK2, which phosphorylate both myelin basic protein (MBP) and a peptide containing Thr669 of the epidermal growth factor receptor. In cell-free extracts made from gingival fibroblasts treated with ... More
Activation of NF-kappaB protects hippocampal neurons against oxidative stress-induced apoptosis: evidence for induction of manganese superoxide dismutase and suppression of peroxynitrite production and protein tyrosine nitration.
AuthorsMattson MP, Goodman Y, Luo H, Fu W, Furukawa K
JournalJ Neurosci Res
PubMed ID9335256
The transcription factor NF-kappaB is expressed in neurons wherein it is activated in response to a variety of stress- and injury-related stimuli including exposure to cytokines such as tumor necrosis factor-alpha (TNFalpha), and excitotoxic and oxidative insults. NF-kappaB may play a role in the anti-death actions of TNFalpha in cultured ... More
Anti-immunoglobulin-induced apoptosis in WEHI 231 cells involves the slow formation of ceramide from sphingomyelin and is blocked by bcl-XL.
AuthorsWiesner DA, Kilkus JP, Gottschalk AR, Quintáns J, Dawson G
JournalJ Biol Chem
PubMed ID9092523
Prolonged (>24 h) exposure to anti-IgM (an antigen surrogate that induces membrane cross-linking and apoptosis) induced a 3-fold increase in the mass of endogenous ceramide measured by 32P labeling by diacylglycerol kinase and a 4-fold increase in ceramide as measured by metabolic labeling with [3H]palmitate in a B-lymphocyte cell line, ... More
Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species. Role of mitochondrial glutathione.
AuthorsGarcía-Ruiz C, Colell A, Marí M, Morales A, Fernández-Checa JC
JournalJ Biol Chem
PubMed ID9111045
Ceramide is a sphingolipid that is generated in the signaling of inflammatory cytokines such as tumor necrosis factor (TNF), which exerts many functional roles depending on the cell type where it is produced. Since TNF cytotoxicity is mediated by overproduction of reactive oxygen species from mitochondria, we have examined the ... More
C2-ceramide primes specifically for the superoxide anion production induced by N-formylmethionylleucyl phenylalanine (fMLP) in human neutrophils.
AuthorsRichard A, Bourgoin S, Naccache PH, L'Heureux GP, Krump E, McColl SR, Pelletier G
JournalBiochim Biophys Acta
PubMed ID8555272
Activated sphingomyelinases release ceramide molecules believed to be involved in intracellular signalling. The present study investigated whether soluble C2-ceramide modulates some of the effects of N-formylmethionylleucyl phenylalanine (fMLP) and other agonists on human neutrophils (or polymorphonuclear leukocytes-PMN); principally superoxide anion (O2-) production. The preincubation of PMN for 15 min with ... More
Biosynthesis of N-acetylsphingosine by platelet-activating factor: sphingosine CoA-independent transacetylase in HL-60 cels.
AuthorsLee TC, Ou MC, Shinozaki K, Malone B, Snyder F
JournalJ Biol Chem
PubMed ID8550561
We have previously identified a novel CoA-independent transacetylase in the membrane fraction of HL-60 cells that transfers the acetate group from platelet activating factor (PAF) to a variety of lysophospholipid acceptors (Lee, T.-c., Uemura, Y., and Snyder, F. (1992) J. Biol. Chem. 267, 19992-20001). In the present study, we demonstrate ... More
Membrane-destabilizing properties of C2-ceramide may be responsible for its ability to inhibit platelet aggregation.
AuthorsSimon CG, Gear AR
JournalBiochemistry
PubMed ID9485333
We have studied the effects of short-chain ceramides on platelet structure and function. N-Acetylsphingosine (C2-ceramide), a cell-permeable short-chain analogue, and N-acetyldihydrosphingosine (C2-dihydroceramide), which lacks the 4-5 double bond, have been investigated. C2-Ceramide (15 microM) inhibited ADP-induced aggregation by 50% at a platelet concentration of 1.25 x 10(8)/mL, while it took ... More
Sphingosine-mediated phosphatidylinositol metabolism and calcium mobilization.
AuthorsChao CP, Laulederkind SJ, Ballou LR
JournalJ Biol Chem
PubMed ID8119927
The cytokine-mediated stimulation of sphingomyelin (SM) metabolism is emerging as an important signal transduction pathway via the generation of ceramide and sphingosine, products which have been shown to affect a wide variety of biological processes. Because SM-mediated signal transduction is initiated via the hydrolysis of an integral membrane phospholipid by ... More
Bimodal regulation of ceramidase by interleukin-1beta. Implications for the regulation of cytochrome p450 2C11.
AuthorsNikolova-Karakashian M, Morgan ET, Alexander C, Liotta DC, Merrill AH
JournalJ Biol Chem
PubMed ID9228043
Interleukin 1beta (IL-1beta) induces the hydrolysis of sphingomyelin (SM) to ceramide (Cer) in primary cultures of rat hepatocytes, and Cer has been proposed to play a role in the down-regulation of cytochrome P450 2C11 (CYP2C11) and induction of alpha1-acid glycoprotein (AGP) by this cytokine (Chen, J., Nikolova-Karakashian, M., Merrill, A. ... More
The dimeric and catalytic subunit forms of protein phosphatase 2A from rat brain are stimulated by C2-ceramide.
AuthorsLaw B, Rossie S
JournalJ Biol Chem
PubMed ID7759536
Protein phosphatase 2A (PP-2A) is a heterotrimeric enzyme consisting of a catalytic (C) subunit and A and B regulatory subunits. PP-2A is activated by ceramide in vitro suggesting that PP-2A may be a target of this putative second messenger in vivo (Dobrowsky, R. T., Kamibayashi, C., Mumby, M. C., and ... More
Antagonism of immunostimulatory CpG-oligodeoxynucleotides by quinacrine, chloroquine, and structurally related compounds.
AuthorsMacfarlane DE, Manzel L
JournalJ Immunol
PubMed ID9570525
Phosphorothioate oligodeoxynucleotides containing CpG (CpG-ODN) activate immune responses. We report that quinacrine, chloroquine, and structurally related compounds completely inhibit the antiapoptotic effect of CpG-ODN on WEHI 231 murine B lymphoma cells and inhibit CpG-ODN-induced secretion of IL-6 by WEHI 231. They also inhibit IL-6 synthesis and thymidine uptake by human ... More
Selective involvement of ceramide in cytokine-induced apoptosis. Ceramide inhibits phorbol ester activation of nuclear factor kappaB.
AuthorsGamard CJ, Dbaibo GS, Liu B, Obeid LM, Hannun YA
JournalJ Biol Chem
PubMed ID9195956
Among its diverse biologic effects, the cytokine tumor necrosis factor alpha causes the rapid nuclear translocation of the transcription factor, nuclear factor kappaB (NF-kappaB). The p55 tumor necrosis factor (TNF) receptor shares with the related APO-1/Fas antigen the ability to initiate apoptosis. We investigated the role of the sphingolipid mediator ... More
Cell-permeable ceramide inhibits the growth of B lymphoma Raji cells lacking TNF-alpha-receptors by inducing G0/G1 arrest but not apoptosis: a new model for dissecting cell-cycle arrest and apoptosis.
AuthorsKuroki J, Hirokawa M, Kitabayashi A, Lee M, Horiuchi T, Kawabata Y, Miura AB
JournalLeukemia
PubMed ID8946936
We examined the effects of a cell-permeable ceramide analog, C2-ceramide, on the growth of TNF-alpha-resistant B lymphoma Raji cells lacking TNF-alpha-receptors (TNF-R). C2-ceramide inhibited the clonal growth of not only TNF-alpha-sensitive myeloid leukemia cells (HL60 and U937) but also Raji cells. Following stimulation with C2-ceramide, HL60 and U937 cells showed ... More
Cell-permeable ceramides inhibit the stimulation of DNA synthesis and phospholipase D activity by phosphatidate and lysophosphatidate in rat fibroblasts.
AuthorsGomez-Muñoz A, Martin A, O'Brien L, Brindley DN
JournalJ Biol Chem
PubMed ID8132631
The interactions of ceramides with phosphatidate and lysophosphatidate in the regulation of signal transduction in rat fibroblasts were examined. C2- and C6-ceramides (N-acetylsphingosine and N-hexanoylsphingosine, respectively) at 10 microM inhibited the stimulation of DNA synthesis that was produced by 50-100 microM phosphatidate, or lysophosphatidate, or by exogenous phospholipase D. Sphingosine ... More
C2-Ceramide increases cytoplasmic calcium concentrations in human parathyroid cells.
AuthorsMihai R, Lai T, Schofield G, Farndon JR
JournalBiochem Biophys Res Commun
PubMed ID10679256
Effects of extracellular calcium ([Ca(2+)](ext)) on parathyroid cells are mainly due to the activation of a plasma membrane calcium receptor (CaR) coupled with release of intracellular calcium. In addition, high [Ca(2+)](ext) activates the sphingomyelin pathway in bovine parathyroid cells, generating ceramides and sphingosine. This study explored the direct effects of ... More
Ceramide inhibits IgE-mediated activation of phospholipase D, but not of phospholipase C, in rat basophilic leukemia (RBL-2H3) cells.
AuthorsNakamura Y, Nakashima S, Ojio K, Banno Y, Miyata H, Nozawa Y
JournalJ Immunol
PubMed ID8598470
Ceramide, a product of sphingomyelin hydrolysis by sphingomyelinase, elicits various cellular functions and has recently been regarded as a second messenger. To investigate the role of ceramide in rat basophilic leukemia (RBL-2H3) cells, the effects of a cell-permeable analogue, N-acetylsphingosine (C2-ceramide), on Ag-mediated cellular responses were examined. C2-Ceramide inhibited Ag- ... More
Mitochondrial free calcium levels (Rhod-2 fluorescence) and ultrastructural alterations in neuronally differentiated PC12 cells during ceramide-dependent cell death.
AuthorsMuriel MP, Lambeng N, Darios F, Michel PP, Hirsch EC, Agid Y, Ruberg M
JournalJ Comp Neurol
PubMed ID10982470
Mitochondrial free calcium levels measured by Rhod-2 fluorescence and ultrastructure were examined during cell death in nerve growth factor (NGF)-differentiated PC12 cells that were 1) exposed to C2-ceramide, 2) deprived of serum to induce endogenous ceramide production, or 3) treated with calcium ionophore A23187. Rhod-2 fluorescence in mitochondria and also ... More
Ceramide activates heterotrimeric protein phosphatase 2A.
AuthorsDobrowsky RT, Kamibayashi C, Mumby MC, Hannun YA
JournalJ Biol Chem
PubMed ID8393446
Ceramide activates a cytosolic protein phosphatase present in rat T9 glioma cells and rat brain. Ceramide-activated protein phosphatase (CAPP) was found to share several properties with protein phosphatase 2A (PP2A) leading to the hypothesis that ceramide may directly activate PP2A. PP2A was isolated as a heterotrimer (AB'C, AB alpha C), ... More
Sphingosine induces p125FAK and paxillin tyrosine phosphorylation, actin stress fiber formation, and focal contact assembly in Swiss 3T3 cells.
AuthorsSeufferlein T, Rozengurt E
JournalJ Biol Chem
PubMed ID7525558
Treatment of Swiss 3T3 cells with sphingosine, a potential breakdown product of all sphingolipids, induced tyrosine phosphorylation of multiple substrates including bands of M(r) 110,000-130,000 and M(r) 70,000-80,000. Tyrosine phosphorylation in response to sphingosine occurred in a concentration dependent manner (EC50 = 10 microM) and developed gradually reaching half maximum ... More
Interleukin-1 beta-induced ceramide and diacylglycerol generation may lead to activation of the c-Jun NH2-terminal kinase and the transcription factor ATF2 in the insulin-producing cell line RINm5F.
AuthorsWelsh N
JournalJ Biol Chem
PubMed ID8626526
The aim of this investigation was to study the putative involvement of lipid second messengers, protein kinases, and transcription factors in interleukin-1 beta (IL-1beta)-induced signal transduction in insulin-producing cells. For this purpose, insulin-producing RINm5F cells were exposed to IL-1beta (25 units/ml), and the ceramide, ceramide 1-phosphate, sphingomyelin, diacylglycerol, and phosphatidic ... More
Ceramides modulate protein kinase C activity and perturb the structure of Phosphatidylcholine/Phosphatidylserine bilayers.
AuthorsHuang HW, Goldberg EM, Zidovetzki R
JournalBiophys J
PubMed ID10465759
We studied the effects of natural ceramide and a series of ceramide analogs with different acyl chain lengths on the activity of rat brain protein kinase C (PKC) and on the structure of bovine liver phosphatidylcholine (BLPC)/dipalmitoylphosphatidylcholine (DPPC)/dipalmitoylphosphatidylserine (DPPS) (3:1:1 molar ratio) bilayers using (2)H-NMR and specific enzymatic assays in ... More
The transcription factor NF-kappaB mediates increases in calcium currents and decreases in NMDA- and AMPA/kainate-induced currents induced by tumor necrosis factor-alpha in hippocampal neurons.
AuthorsFurukawa K, Mattson MP
JournalJ Neurochem
PubMed ID9572271
Tumor necrosis factor-alpha (TNF alpha) is a cytokine rapidly produced in the brain in response to vigorous neuronal activity and tissue injury. TNF alpha may protect neurons against excitotoxic and oxidative insults by a mechanism involving activation of the transcription factor NF-kappaB. Whole-cell perforated patch clamp recordings in cultured rat ... More
Cell cycle arrest induced by an inhibitor of glucosylceramide synthase. Correlation with cyclin-dependent kinases.
AuthorsRani CS, Abe A, Chang Y, Rosenzweig N, Saltiel AR, Radin NS, Shayman JA
JournalJ Biol Chem
PubMed ID7852361
In an attempt to define the basis for sphingolipid regulation of cell proliferation, we studied the effects of glucosylceramide (GlcCer) synthase inhibition by threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on NIH 3T3 cells overexpressing insulin-like growth factor-1 (IGF-1) receptor. PDMP treatment resulted in a time-dependent decrease in GlcCer levels and an increase in cellular ... More
Oxidized low density lipoprotein induces apoptosis in cultured human umbilical vein endothelial cells by common and unique mechanisms.
AuthorsHarada-Shiba M, Kinoshita M, Kamido H, Shimokado K
JournalJ Biol Chem
PubMed ID9545302
Oxidized low density lipoprotein (oxLDL) induces apoptosis in vascular cells. To elucidate the mechanisms involved in this apoptosis, we studied the apoptosis-inducing activity in lipid fractions of oxLDL and the roles of two common mechanisms, ceramide generation and the activation of caspases, in apoptosis in human umbilical vein endothelial cells ... More
Ceramide inactivates cellular protein kinase Calpha.
AuthorsLee JY, Hannun YA, Obeid LM
JournalJ Biol Chem
PubMed ID8662781
Ceramide mediates the effects of extracellular agents on cellular growth, differentiation and apoptosis. In this study, we explored the mechanisms by which ceramide induces its cellular effects. In Molt-4 cells, phorbol 12-myristate 13-acetate (PMA) induced retinoblastoma gene product (Rb) phosphorylation, and ceramide inhibited this effect, suggesting an inhibitory effect of ... More