Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 27 March 1992:
Vol. 255. no. 5052, pp. 1715 - 1718
DOI: 10.1126/science.1313189
Prev | Table of Contents | Next

Articles

Science, Vol 255, Issue 5052, 1715-1718
Copyright © 1992 by American Association for the Advancement of Science

articles

Tumor necrosis factor-alpha activates the sphingomyelin signal transduction pathway in a cell-free system

KA Dressler, S Mathias, and RN Kolesnick

Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

The mechanism of tumor necrosis factor (TNF)-alpha signaling is unknown. TNF-alpha signaling may involve sphingomyelin hydrolysis to ceramide by a sphingomyelinase and stimulation of a ceramide-activated protein kinase. In a cell-free system, TNF-alpha induced a rapid reduction in membrane sphingomyelin content and a quantitative elevation in ceramide concentrations. Ceramide-activated protein kinase activity also increased. Kinase activation was mimicked by addition of sphingomyelinase but not by phospholipases A2, C, or D. Reconstitution of this cascade in a cell-free system demonstrates tight coupling to the receptor, suggesting this is a signal transduction pathway for TNF-alpha.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I.
A. B. Ghering and W. S. Davidson (2006)
J. Lipid Res. 47, 2781-2788
   Abstract »    Full Text »    PDF »
Substrate specificity of human ceramide kinase.
D. S. Wijesinghe, A. Massiello, P. Subramanian, Z. Szulc, A. Bielawska, and C. E. Chalfant (2005)
J. Lipid Res. 46, 2706-2716
   Abstract »    Full Text »    PDF »
Myocardial protective effect of FR167653; a novel cytokine inhibitor in ischemic-reperfused rat heart.
A. Aleshin, Y. Sawa, M. Ono, T. Funatsu, S. Miyagawa, and H. Matsuda (2004)
Eur. J. Cardiothorac. Surg. 26, 974-980
   Abstract »    Full Text »    PDF »
Sphingosine Kinase Protects Lipopolysaccharide-Activated Macrophages from Apoptosis.
W. Wu, R. D. Mosteller, and D. Broek (2004)
Mol. Cell. Biol. 24, 7359-7369
   Abstract »    Full Text »    PDF »
Desensitization of the Permeability Transition Pore by Cyclosporin A Prevents Activation of the Mitochondrial Apoptotic Pathway and Liver Damage by Tumor Necrosis Factor-{alpha}.
M. E. Soriano, L. Nicolosi, and P. Bernardi (2004)
J. Biol. Chem. 279, 36803-36808
   Abstract »    Full Text »    PDF »
Role of FAN in Tumor Necrosis Factor-{alpha} and Lipopolysaccharide-induced Interleukin-6 Secretion and Lethality in D-Galactosamine-sensitized Mice.
S. Malagarie-Cazenave, B. Segui, S. Leveque, V. Garcia, S. Carpentier, M.-F. Altie, A. Brouchet, V. Gouaze, N. Andrieu-Abadie, Y. Barreira, et al. (2004)
J. Biol. Chem. 279, 18648-18655
   Abstract »    Full Text »    PDF »
Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death.
F. Darios, O. Corti, C. B. Lucking, C. Hampe, M.-P. Muriel, N. Abbas, W.-J. Gu, E. C. Hirsch, T. Rooney, M. Ruberg, et al. (2003)
Hum. Mol. Genet. 12, 517-526
   Abstract »    Full Text »    PDF »
Side-Stream Cigarette Smoke Induces Dose-Response in Systemic Inflammatory Cytokine Production and Oxidative Stress.
J. Zhang, Y. Liu, J. Shi, D. F. Larson, and R. R. Watson (2002)
Experimental Biology and Medicine 227, 823-829
   Abstract »    Full Text »    PDF »
Synthetic Phytoceramides Induce Apoptosis with Higher Potency than Ceramides.
O. Hwang, G. Kim, Y. J. Jang, S. W. Kim, G. Choi, H. J. Choi, S. Y. Jeon, D. G. Lee, and J. D. Lee (2001)
Mol. Pharmacol. 59, 1249-1255
   Abstract »    Full Text »
Subtype-Specific Translocation of the {delta} Subtype of Protein Kinase C and Its Activation by Tyrosine Phosphorylation Induced by Ceramide in HeLa Cells.
T. Kajimoto, S. Ohmori, Y. Shirai, N. Sakai, and N. Saito (2001)
Mol. Cell. Biol. 21, 1769-1783
   Abstract »    Full Text »    PDF »
Sphingolipids and cholesterol modulate membrane susceptibility to cytosolic phospholipase A2.
E. Klapisz, J. Masliah, G. Béréziat, C. Wolf, and K. S. Koumanov (2000)
J. Lipid Res. 41, 1680-1688
   Abstract »    Full Text »
Differential Effects of Sphingomyelin Hydrolysis and Resynthesis on the Activation of NF-kappa B in Normal and SV40-transformed Human Fibroblasts.
C. Luberto, D. S. Yoo, H. S. Suidan, G. M. Bartoli, and Y. A. Hannun (2000)
J. Biol. Chem. 275, 14760-14766
   Abstract »    Full Text »    PDF »
Ceramide Path in Human Lung Cell Death.
C. Chan and T. Goldkorn (2000)
Am. J. Respir. Cell Mol. Biol. 22, 460-468
   Abstract »    Full Text »
Down-Regulation of Ceramide Production Abrogates Ionizing Radiation-Induced Cytochrome c Release and Apoptosis.
S. J. Chmura, E. Nodzenski, S. Kharbanda, P. Pandey, J. Quintans, D. W. Kufe, and R. R. Weichselbaum (2000)
Mol. Pharmacol. 57, 792-796
   Abstract »    Full Text »
Mass Spectrometric Identification of Increased C16 Ceramide Levels During Apoptosis.
R. L. Thomas Jr., C. M. Matsko, M. T. Lotze, and A. A. Amoscato (1999)
J. Biol. Chem. 274, 30580-30588
   Abstract »    Full Text »    PDF »
12-O-tetradecanoylphorbol-13-acetate-induced Apoptosis Is Mediated by Tumor Necrosis Factor alpha in Human Monocytic U937 Cells.
Y. Takada, M. Hachiya, Y. Osawa, Y. Hasegawa, K. Ando, Y. Kobayashi, and M. Akashi (1999)
J. Biol. Chem. 274, 28286-28292
   Abstract »    Full Text »    PDF »
Tumor Necrosis Factor-{alpha} Stimulates Lactate Dehydrogenase A Expression in Porcine Cultured Sertoli Cells: Mechanisms of Action.
F. Boussouar, R. Grataroli, J. Ji, and M. Benahmed (1999)
Endocrinology 140, 3054-3062
   Abstract »    Full Text »
Tumor Necrosis Factor alpha  Stimulates Lipolysis in Adipocytes by Decreasing Gi Protein Concentrations.
S. Gasic, B. Tian, and A. Green (1999)
J. Biol. Chem. 274, 6770-6775
   Abstract »    Full Text »    PDF »
Immunosuppressive Leflunomide Metabolite (A77 1726) Blocks TNF-Dependent Nuclear Factor-{kappa}B Activation and Gene Expression.
S. K. Manna and B. B. Aggarwal (1999)
J. Immunol. 162, 2095-2102
   Abstract »    Full Text »    PDF »
Interleukin-1{beta} and Catecholamines Synergistically Stimulate Interleukin-6 Release from Rat C6 Glioma Cells in Vitro: a Potential Role for Lysophosphatidylcholine.
J. W. Zumwalt, B. J. Thunstrom, and B. L. Spangelo (1999)
Endocrinology 140, 888-896
   Abstract »    Full Text »
Novel ceramides recovered from Porphyromonas gingivalis: relationship to adult periodontitis.
F. C. Nichols (1998)
J. Lipid Res. 39, 2360-2372
   Abstract »    Full Text »
BAD Enables Ceramide to Signal Apoptosis via Ras and Raf-1.
S. Basu, S. Bayoumy, Y. Zhang, J. Lozano, and R. Kolesnick (1998)
J. Biol. Chem. 273, 30419-30426
   Abstract »    Full Text »    PDF »
TNF-alpha -induced endothelium-independent vasodilation: a role for phospholipase A2-dependent ceramide signaling.
D. G. Johns and R. C. Webb (1998)
Am J Physiol Heart Circ Physiol 275, H1592-H1598
   Abstract »    Full Text »    PDF »
Analysis of Human Breast Adenocarcinoma MCF7 Resistance to Tumor Necrosis Factor-induced Cell Death. LACK OF CORRELATION BETWEEN JNK ACTIVATION AND CERAMIDE PATHWAY.
M. Ameyar, A. Atfi, Z. Cai, R. Stancou, V. Shatrov, A. Bettaieb, and S. Chouaib (1998)
J. Biol. Chem. 273, 29002-29008
   Abstract »    Full Text »    PDF »
Activation of a Plasma Membrane-Associated Neutral Sphingomyelinase and Concomitant Ceramide Accumulation During IgG-Dependent Phagocytosis in Human Polymorphonuclear Leukocytes.
V. Hinkovska-Galcheva, L. Kjeldsen, P. J. Mansfield, L. A. Boxer, J. A. Shayman, and S. J. Suchard (1998)
Blood 91, 4761-4769
   Abstract »    Full Text »    PDF »
Fas-Induced Apoptosis in Rat Thecal/Interstitial Cells Signals Through Sphingomyelin-Ceramide Pathway.
A. Foghi, A. Ravandi, K. J. Teerds, H. van der Donk, A. Kuksis, and J. Dorrington (1998)
Endocrinology 139, 2041-2047
   Abstract »    Full Text »    PDF »
Cloned mammalian neutral sphingomyelinase: Functions in sphingolipid signaling?.
S. Tomiuk, K. Hofmann, M. Nix, M. Zumbansen, and W. Stoffel (1998)
PNAS 95, 3638-3643
   Abstract »    Full Text »    PDF »
Ceramide Formation Leads to Caspase-3 Activation during Hypoxic PC12 Cell Death. INHIBITORY EFFECTS OF Bcl-2 ON CERAMIDE FORMATION AND CASPASE-3 ACTIVATION.
S.-i. Yoshimura, Y. Banno, S. Nakashima, K. Takenaka, H. Sakai, Y. Nishimura, N. Sakai, S. Shimizu, Y. Eguchi, Y. Tsujimoto, et al. (1998)
J. Biol. Chem. 273, 6921-6927
   Abstract »    Full Text »    PDF »
Nuclear Targeted Suppression of NF-{kappa}B Activity by the Novel Quinone Derivative E3330.
M. Hiramoto, N. Shimizu, K. Sugimoto, J. Tang, Y. Kawakami, M. Ito, S. Aizawa, H. Tanaka, I. Makino, and H. Handa (1998)
J. Immunol. 160, 810-819
   Abstract »    Full Text »    PDF »
H2O2 acts on cellular membranes to generate ceramide signaling and initiate apoptosis in tracheobronchial epithelial cells.
T Goldkorn, N Balaban, M Shannon, V Chea, K Matsukuma, D Gilchrist, H Wang, and C Chan (1998)
J. Cell Sci. 111, 3209-3220
   Abstract »    PDF »
Intracellular Staphylococcus aureus Escapes the Endosome and Induces Apoptosis in Epithelial Cells.
K. W. Bayles, C. A. Wesson, L. E. Liou, L. K. Fox, G. A. Bohach, and W. R. Trumble (1998)
Infect. Immun. 66, 336-342
   Abstract »    Full Text »    PDF »
Activation of CPP32-like Proteases Is Not Sufficient to Trigger Apoptosis: Inhibition of Apoptosis by Agents that Suppress Activation of AP24, but Not CPP32-like Activity.
S. C. Wright, U. Schellenberger, H. Wang, D. H. Kinder, J. W. Talhouk, and J. W. Larrick (1997)
J. Exp. Med. 186, 1107-1117
   Abstract »    Full Text »    PDF »
Fas-induced apoptosis of T cells occurs independently of ceramide generation.
J. D. Watts, M. Gu, A. J. Polverino, S. D. Patterson, and R. Aebersold (1997)
PNAS 94, 7292-7296
   Abstract »    Full Text »    PDF »
Selective Involvement of Ceramide in Cytokine-induced Apoptosis. CERAMIDE INHIBITS PHORBOL ESTER ACTIVATION OF NUCLEAR FACTOR kappa B.
C. J. Gamard, G. S. Dbaibo, B. Liu, L. M. Obeid, and Y. A. Hannun (1997)
J. Biol. Chem. 272, 16474-16481
   Abstract »    Full Text »    PDF »
Expression of Neutral Sphingomyelinase Identifies a Distinct Pool of Sphingomyelin Involved in Apoptosis.
P. Zhang, B. Liu, G. M. Jenkins, Y. A. Hannun, and L. M. Obeid (1997)
J. Biol. Chem. 272, 9609-9612
   Abstract »    Full Text »    PDF »
TAK1 Mediates the Ceramide Signaling to Stress-activated Protein Kinase/c-Jun N-terminal Kinase.
K. Shirakabe, K. Yamaguchi, H. Shibuya, K. Irie, S. Matsuda, T. Moriguchi, Y. Gotoh, K. Matsumoto, and E. Nishida (1997)
J. Biol. Chem. 272, 8141-8144
   Abstract »    Full Text »    PDF »
Organized Endothelial Cell Surface Signal Transduction in Caveolae Distinct from Glycosylphosphatidylinositol-anchored Protein Microdomains.
J. Liu, P. Oh, T. Horner, R. A. Rogers, and J. E. Schnitzer (1997)
J. Biol. Chem. 272, 7211-7222
   Abstract »    Full Text »    PDF »
Inhibition of Carnitine Palmitoyltransferase I Augments Sphingolipid Synthesis and Palmitate-induced Apoptosis.
M. B. Paumen, Y. Ishida, M. Muramatsu, M. Yamamoto, and T. Honjo (1997)
J. Biol. Chem. 272, 3324-3329
   Abstract »    Full Text »    PDF »
Elevation of Ceramide within Distal Neurites Inhibits Neurite Growth in Cultured Rat Sympathetic Neurons.
E. I.P. de Chaves, M. Bussiere, D. E. Vance, R. B. Campenot, and J. E. Vance (1997)
J. Biol. Chem. 272, 3028-3035
   Abstract »    Full Text »    PDF »
Ceramide-induced Translocation of Protein Kinase C-delta and -epsilon to the Cytosol. IMPLICATIONS IN APOPTOSIS.
H. Sawai, T. Okazaki, Y. Takeda, M. Tashima, H. Sawada, M. Okuma, S. Kishi, H. Umehara, and N. Domae (1997)
J. Biol. Chem. 272, 2452-2458
   Abstract »    Full Text »    PDF »
Ceramide Is Not a Signal for Tumor Necrosis Factor–Induced Gene Expression but Does Cause Programmed Cell Death in Human Vascular Endothelial Cells.
M. R. Slowik, L. G. De Luca, W. Min, and J. S. Pober (1996)
Circ. Res. 79, 736-747
   Abstract »    Full Text »
c-Jun Is a Downstream Target for Ceramide-activated Protein Phosphatase in A431 Cells.
J. G. Reyes, I. G. Robayna, P. S. Delgado, I. H. Gonzalez, J. Q. Aguiar, F. E. Rosas, L. F. Fanjul, and C. M.R. d. Galarreta (1996)
J. Biol. Chem. 271, 21375-21380
   Abstract »    Full Text »    PDF »
The Sphingomyelin-Ceramide Signaling Pathway Is Involved in Oxidized Low Density Lipoprotein-induced Cell Proliferation.
N. Auge, N. Andrieu, A. Negre-Salvayre, J.-C. Thiers, T. Levade, and R. Salvayre (1996)
J. Biol. Chem. 271, 19251-19255
   Abstract »    Full Text »    PDF »
Accumulation of Glucosylceramides in Multidrug-resistant Cancer Cells.
Y. Lavie, H.-t. Cao, S. L. Bursten, A. E. Giuliano, and M. C. Cabot (1996)
J. Biol. Chem. 271, 19530-19536
   Abstract »    Full Text »    PDF »
Endothelial Cell Inflammatory Responses to Tumor Necrosis Factor alpha . CERAMIDE-DEPENDENT AND -INDEPENDENT MITOGEN-ACTIVATED PROTEIN KINASE CASCADES.
V. Modur, G. A. Zimmerman, S. M. Prescott, and T. M. McIntyre (1996)
J. Biol. Chem. 271, 13094-13102
   Abstract »    Full Text »    PDF »
Ceramide Inactivates Cellular Protein Kinase Calpha.
J. Y. Lee, Y. A. Hannun, and L. M. Obeid (1996)
J. Biol. Chem. 271, 13169-13174
   Abstract »    Full Text »    PDF »
(1S,2R)-D-erythro-2-(N-Myristoylamino)-1-phenyl-1-propanol as an Inhibitor of Ceramidase.
A. Bielawska, M. S. Greenberg, D. Perry, S. Jayadev, J. A. Shayman, C. McKay, and Y. A. Hannun (1996)
J. Biol. Chem. 271, 12646-12654
   Abstract »    Full Text »    PDF »
Inhibition of Tumor Necrosis Factor-induced p42/p44 Mitogen-Activated Protein Kinase Activation by Sodium Salicylate.
P. Schwenger, E. Y. Skolnik, and J. Vilcek (1996)
J. Biol. Chem. 271, 8089-8094
   Abstract »    Full Text »    PDF »
A Physical Interaction between the Cell Death Protein Fas and the Tyrosine Kinase p59[IMAGE].
E. A. Atkinson, H. Ostergaard, K. Kane, M. J. Pinkoski, A. Caputo, M. W. Olszowy, and R. C. Bleackley (1996)
J. Biol. Chem. 271, 5968-5971
   Abstract »    Full Text »    PDF »
A ceramide-activated protein phosphatase mediates ceramide-induced G1 arrest of Saccharomyces cerevisiae..
J T Nickels and J R Broach (1996)
Genes & Dev. 10, 382-394
   Abstract »    PDF »
Requirement of AP-1 for Ceramide-induced Apoptosis in Human Leukemia HL-60 Cells.
H. Sawai, T. Okazaki, H. Yamamoto, H. Okano, Y. Takeda, M. Tashima, H. Sawada, M. Okuma, H. Ishikura, H. Umehara, et al. (1995)
J. Biol. Chem. 270, 27326-27331
   Abstract »    Full Text »    PDF »
Activation of Transcription Factor NF-kappaB Is Suppressed by Curcumin (Diferuloylmethane).
S. Singh and B. B. Aggarwal (1995)
J. Biol. Chem. 270, 24995-25000
   Abstract »    Full Text »    PDF »
Low Temperatures and Hypertonicity Do Not Block Cytokine-induced Stimulation of the Sphingomyelin Pathway but Inhibit Nuclear Factor-kappaB Activation.
N. Andrieu, R. Salvayre, J.-P. Jaffrézou, and T. Levade (1995)
J. Biol. Chem. 270, 24518-24524
   Abstract »    Full Text »    PDF »
Casein Kinase-1 Phosphorylates the p75 Tumor Necrosis Factor Receptor and Negatively Regulates Tumor Necrosis Factor Signaling for Apoptosis.
R. Beyaert, B. Vanhaesebroeck, W. Declercq, J. Van Lint, P. Vandenabeele, P. Agostinis, J. R. Vandenheede, and W. Fiers (1995)
J. Biol. Chem. 270, 23293-23299
   Abstract »    Full Text »    PDF »
Differential Regulation of Sphingomyelinase and Ceramidase Activities by Growth Factors and Cytokines.
E. Coroneos, M. Martinez, S. McKenna, and M. Kester (1995)
J. Biol. Chem. 270, 23305-23309
   Abstract »    Full Text »    PDF »
Sphingolipid Biosynthesis de Novo by Rat Hepatocytes in Culture.
A. H. Merrill Jr., S. Lingrell, E. Wang, M. Nikolova-Karakashian, T. R. Vales, and D. E. Vance (1995)
J. Biol. Chem. 270, 13834-13841
   Abstract »    Full Text »    PDF »
Ceramide As a Modulator of Endocytosis.
C.-S. Chen, A. G. Rosenwald, and R. E. Pagano (1995)
J. Biol. Chem. 270, 13291-13297
   Abstract »    Full Text »    PDF »
Ceramide Reverses Brefeldin A (BFA) Resistance in BFA-resistant Cell Lines.
T. Oda, C.-H. Chen, and H. C. Wu (1995)
J. Biol. Chem. 270, 4088-4092
   Abstract »    Full Text »    PDF »
Role for Ceramide in Cell Cycle Arrest.
S. Jayadev, B. Liu, A. E. Bielawska, J. Y. Lee, F. Nazaire, M. Yu. Pushkareva, L. M. Obeid, and Y. A. Hannun (1995)
J. Biol. Chem. 270, 2047-2052
   Abstract »    Full Text »    PDF »
Induction of human tenascin (neuronectin) by growth factors and cytokines: cell type-specific signals and signalling pathways.
W. Rettig, H. Erickson, A. Albino, and P Garin-Chesa (1994)
J. Cell Sci. 107, 487-497
   Abstract »    PDF »
Activation of the sphingomyelin signaling pathway in intact EL4 cells and in a cell-free system by IL-1 beta.
S Mathias, A Younes, C. Kan, I Orlow, C Joseph, and R. Kolesnick (1993)
Science 259, 519-522
   Abstract »    PDF »
Ceramide Inhibits Axonal Growth and Nerve Growth Factor Uptake without Compromising the Viability of Sympathetic Neurons.
E. P. de Chaves, M. Bussiere, B. MacInnis, D. E. Vance, R. B. Campenot, and J. E. Vance (2001)
J. Biol. Chem. 276, 36207-36214
   Abstract »    Full Text »    PDF »
FAS Activation Induces Dephosphorylation of SR Proteins. DEPENDENCE ON THE DE NOVO GENERATION OF CERAMIDE AND ACTIVATION OF PROTEIN PHOSPHATASE 1.
C. E. Chalfant, B. Ogretmen, S. Galadari, B.-J. Kroesen, B. J. Pettus, and Y. A. Hannun (2001)
J. Biol. Chem. 276, 44848-44855
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)