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Science 13 December 1996:
Vol. 274. no. 5294, pp. 1855 - 1859
DOI: 10.1126/science.274.5294.1855
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Articles

Functions of Ceramide in Coordinating Cellular Responses to Stress

Yusuf A. Hannun

Sphingolipid metabolites participate in key events of signal transduction and cell regulation. In the sphingomyelin cycle, a number of extracellular agents and insults (such as tumor necrosis factor, Fas ligands, and chemotherapeutic agents) cause the activation of sphingomyelinases, which act on membrane sphingomyelin and release ceramide. Multiple experimental approaches suggest an important role for ceramide in regulating such diverse responses as cell cycle arrest, apoptosis, and cell senescence. In vitro, ceramide activates a serine-threonine protein phosphatase, and in cells it regulates protein phosphorylation as well as multiple downstream targets [such as interleukin converting enzyme (ICE)-like proteases, stress-activated protein kinases, and the retinoblastoma gene product] that mediate its distinct cellular effects. This spectrum of inducers of ceramide accumulation and the nature of ceramide-mediated responses suggest that ceramide is a key component of intracellular stress response pathways.

The author is in the Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

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   Abstract »    Full Text »    PDF »
Ceramide in the antiapoptotic effect of ischemic preconditioning.
L. Argaud, A.-F. Prigent, L. Chalabreysse, J. Loufouat, M. Lagarde, and M. Ovize (2004)
Am J Physiol Heart Circ Physiol 286, H246-H251
   Abstract »    Full Text »    PDF »
Resistance to different classes of drugs is associated with impaired apoptosis in childhood acute lymphoblastic leukemia.
A. Holleman, M. L. d. Boer, K. M. Kazemier, G. E. Janka-Schaub, and R. Pieters (2003)
Blood 102, 4541-4546
   Abstract »    Full Text »    PDF »
Mitochondrial Cytochrome c Release Mediates Ceramide-induced Activator Protein 2 Activation and Gene Expression in Keratinocytes.
S. Grether-Beck, I. Felsner, H. Brenden, and J. Krutmann (2003)
J. Biol. Chem. 278, 47498-47507
   Abstract »    Full Text »    PDF »
Liposomal Delivery Enhances Short-Chain Ceramide-Induced Apoptosis of Breast Cancer Cells.
T. Stover and M. Kester (2003)
J. Pharmacol. Exp. Ther. 307, 468-475
   Abstract »    Full Text »    PDF »
Sphingosine-1-Phosphate Inhibition of Apoptosis Requires Mitogen-Activated Protein Kinase Phosphatase-1 in Mouse Fibroblast C3H10T1/2 Cells.
S. S. Castillo and D. Teegarden (2003)
J. Nutr. 133, 3343-3349
   Abstract »    Full Text »    PDF »
Role of Human Sphingosine-1-phosphate Phosphatase 1 in the Regulation of Intra- and Extracellular Sphingosine-1-phosphate Levels and Cell Viability.
K. R. Johnson, K. Y. Johnson, K. P. Becker, J. Bielawski, C. Mao, and L. M. Obeid (2003)
J. Biol. Chem. 278, 34541-34547
   Abstract »    Full Text »    PDF »
Metabolism of the unnatural anticancer lipid safingol, L-threo-dihydrosphingosine, in cultured cells.
M. Dragusin, C. Gurgui, G. Schwarzmann, J. Hoernschemeyer, and G. van Echten-Deckert (2003)
J. Lipid Res. 44, 1772-1779
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Reovirus-Induced Alteration in Expression of Apoptosis and DNA Repair Genes with Potential Roles in Viral Pathogenesis.
R. L. DeBiasi, P. Clarke, S. Meintzer, R. Jotte, B. K. Kleinschmidt-Demasters, G. L. Johnson, and K. L. Tyler (2003)
J. Virol. 77, 8934-8947
   Abstract »    Full Text »    PDF »
Formation and Remodeling of Inositolphosphoceramide during Differentiation of Trypanosoma cruzi from Trypomastigote to Amastigote.
M. L. Salto, L. E. Bertello, M. Vieira, R. Docampo, S. N. J. Moreno, and R. M. de Lederkremer (2003)
Eukaryot. Cell 2, 756-768
   Abstract »    Full Text »    PDF »
The sphingosine kinase 1/sphingosine-1-phosphate pathway mediates COX-2 induction and PGE2 production in response to TNF-{alpha}.
B. J. PETTUS, J. BIELAWSKI, A. M. PORCELLI, D. L. REAMES, K. R. JOHNSON, J. MORROW, C. E. CHALFANT, L. M. OBEID, and Y. A. HANNUN (2003)
FASEB J 17, 1411-1421
   Abstract »    Full Text »    PDF »
Prevalence of Necrosis in C2-Ceramide-Induced Cytotoxicity in NB16 Neuroblastoma Cells.
B. Ramos, J. M. Lahti, E. Claro, and S. Jackowski (2003)
Mol. Pharmacol. 64, 502-511
   Abstract »    Full Text »    PDF »
Sphingolipids suppress preneoplastic rat hepatocytes in vitro and in vivo.
I. Silins, M. Nordstrand, J. Hogberg, and U. Stenius (2003)
Carcinogenesis 24, 1077-1083
   Abstract »    Full Text »    PDF »
Ceramide accumulation precedes caspase-3 activation during apoptosis of A549 human lung adenocarcinoma cells.
T. Ravid, A. Tsaba, P. Gee, R. Rasooly, E. A. Medina, and T. Goldkorn (2003)
Am J Physiol Lung Cell Mol Physiol 284, L1082-L1092
   Abstract »    Full Text »    PDF »
Significant Role of Ceramide Pathway in Experimental Gastric Ulcer Formation in Rats.
K. Uehara, S. Miura, T. Takeuchi, T. Taki, M. Nakashita, M. Adachi, T. Inamura, T. Ogawa, Y. Akiba, H. Suzuki, et al. (2003)
J. Pharmacol. Exp. Ther. 305, 232-239
   Abstract »    Full Text »
A Saccharomyces cerevisiae mutant strain defective in acetyl-CoA carboxylase arrests at the G2/M phase of the cell cycle.
W. Al-Feel, J. C. DeMar, and S. J. Wakil (2003)
PNAS 100, 3095-3100
   Abstract »    Full Text »    PDF »
O-Glycosylation of Mucin-like Domain Retains the Neutral Ceramidase on the Plasma Membranes as a Type II Integral Membrane Protein.
M. Tani, H. Iida, and M. Ito (2003)
J. Biol. Chem. 278, 10523-10530
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beta 1,4-Galactosyltransferase (beta 4GalT)-IV Is Specific for GlcNAc 6-O-Sulfate. beta 4GalT-IV ACTS ON KERATAN SULFATE-RELATED GLYCANS AND A PRECURSOR GLYCAN OF 6-SULFOSIALYL-LEWIS X.
A. Seko, N. Dohmae, K. Takio, and K. Yamashita (2003)
J. Biol. Chem. 278, 9150-9158
   Abstract »    Full Text »    PDF »
Selective Neuromicrovascular Endothelial Cell Death by 8-Iso-Prostaglandin F2{alpha}: Possible Role in Ischemic Brain Injury.
S. Brault, A. K. Martinez-Bermudez, A. M. Marrache, F. Gobeil Jr, X. Hou, M. Beauchamp, C. Quiniou, G. Almazan, C. Lachance, J. Roberts II, et al. (2003)
Stroke 34, 776-782
   Abstract »    Full Text »    PDF »
Protein kinase Czeta mediated Raf-1/extracellular-regulated kinase activation by daunorubicin.
V. M.-D. Mas, H. Hernandez, I. Plo, C. Bezombes, N. Maestre, A. Quillet-Mary, R. Filomenko, C. Demur, J.-P. Jaffrezou, and G. Laurent (2003)
Blood 101, 1543-1550
   Abstract »    Full Text »    PDF »
Transient Mechanoactivation of Neutral Sphingomyelinase in Caveolae to Generate Ceramide.
M. Czarny, J. Liu, P. Oh, and J. E. Schnitzer (2003)
J. Biol. Chem. 278, 4424-4430
   Abstract »    Full Text »    PDF »
Integrative Transformation System for the Metabolic Engineering of the Sphingoid Base-Producing Yeast Pichia ciferrii.
J.-H. Bae, J.-H. Sohn, C.-S. Park, J.-S. Rhee, and E.-S. Choi (2003)
Appl. Envir. Microbiol. 69, 812-819
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Induction by Sphingomyelinase of Shiga Toxin Receptor and Shiga Toxin 2 Sensitivity in Human Microvascular Endothelial Cells.
T. G. Obrig, R. M. Seaner, M. Bentz, C. A. Lingwood, B. Boyd, A. Smith, and W. Narrow (2003)
Infect. Immun. 71, 845-849
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Basic Fibroblast Growth Factor Activates Endothelial Nitric-Oxide Synthase in CHO-K1 Cells via the Activation of Ceramide Synthesis.
T. Florio, S. Arena, A. Pattarozzi, S. Thellung, A. Corsaro, V. Villa, A. Massa, F. Diana, G. Spoto, S. Forcella, et al. (2003)
Mol. Pharmacol. 63, 297-310
   Abstract »    Full Text »    PDF »


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