Inhibition of sphingomyelin hydrolysis: Targeting the lipid mediator ceramide as a key regulator of cellular fate

Current Medicinal Chemistry

Volumn 16, Issue 16, 2009, Pages 1978-2000

  Claus, Ralf A ^a   Dorer, Michael J ^a   Bunck, Alexander C ^a   Deigner, H Peter ^a  

^a JENA UNIVERSITY HOSPITAL   (Germany)

Author keywords

Apoptosis; Inflammation; Rafts; Sphingomyelinase

Indexed keywords

3 O ETHYL SYPHINGOMYELIN; 3 O METHYL SYPHINGOMYELIN; ACYLSPHINGOSINE DEACYLASE; AMITRIPTYLINE; ANTIDEPRESSANT AGENT; C 11 AG; C 11AG; CALCIUM; CERAMIDE; CERAMIDE 1 PHOSPHATE; DESIPRAMINE; FANTOFARONE; GW 4869; IMIPRAMINE; MACQUARIAMYCIN A; MANUMYCIN A; SMA 7; SPHINGOMYELIN; SPHINGOMYELIN PHOSPHODIESTERASE; SPHINGOMYELIN PHOSPHODIESTERASE 1; SPHINGOMYELIN PHOSPHODIESTERASE 2; SPHINGOMYELIN PHOSPHODIESTERASE 3; SPHINGOMYELIN PHOSPHODIESTERASE 4; SPHINGOMYELIN PHOSPHODIESTERASE INHIBITOR; SPHINGOSINE; SPHINGOSINE 1 PHOSPHATE; SPHINGOSINE KINASE; TRICYCLO[4.3.0.1]DECAN 9 YL XANTHOGENATE; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

APOPTOSIS; CALCIUM CELL LEVEL; CARDIOTOXICITY; CELL CYCLE REGULATION; CELL DIFFERENTIATION; CELL SURVIVAL; CELLULAR DISTRIBUTION; CEREBROVASCULAR ACCIDENT; COMPETITIVE INHIBITION; CYSTIC FIBROSIS; DEPRESSION; DISEASE PREDISPOSITION; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME LOCALIZATION; ENZYME REPLACEMENT; HEART CONTRACTION; HEART FAILURE; HEART MUSCLE CELL; HEART OUTPUT; HUMAN; HYDROLYSIS; IC 50; INFLAMMATION; LIPID METABOLISM; LIPOGENESIS; LYSOSOME; LYSOSOME MEMBRANE; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL PERMEABILITY; NIEMANN PICK DISEASE; NONHUMAN; NUCLEOTIDE SEQUENCE; PATHOPHYSIOLOGY; PROTEIN FUNCTION; RESPIRATORY TRACT INFECTION; REVIEW; SENESCENCE; SEPSIS; SHOCK; SIDE EFFECT; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; WILSON DISEASE;

ANIMALS; CELLS; CERAMIDES; HUMANS; HYDROLYSIS; LIPID METABOLISM; SPHINGOMYELIN PHOSPHODIESTERASE; SPHINGOMYELINS;

EID: 68449094453     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986709788682182     Document Type: Review

References (247)

1. Hakomori, S.I. Cell adhesion/recognition and signal transduction through glycosphingolipid microdomain. Glycoconj. J., 2000, 17, 143-51.
2. Lingwood, C.A. Glycolipid receptors for verotoxin and Helicobacter pylori, role in pathology. Biochim. Biophys. Acta, 1999, 1455, 375-86.
3. Hannun, Y.A.; Luberto, C.; Argraves, K.M. Enzymes of sphingolipid metabolism, from modular to integrative signaling. Biochemistry, 2001, 40, 4893-903.
4. Pettus, B.J.; Chalfant, C.E.; Hannun, Y.A. Sphingolipids in inflammation, roles and implications. Curr. Mol. Med., 2004, 4, 405-18.
5. Spiegel, S. Sphingosine 1-phosphate, a prototype of a new class of second messengers. J. Leukoc. Biol., 1999, 65, 341-4.
6. Maceyka, M.; Payne, S.G.; Milstien, S.; Spiegel, S. Sphingosine kinase, sphingosine-1-phosphate, and apoptosis. Biochim. Biophys. Acta, 2002, 1585, 193-201.
7. Bose, R.; Verheij, M.; Haimovitz-Friedman, A.; Scotto, K.; Fuks, Z.; Kolesnick, R. Ceramide synthase mediates daunorubicin-induced apoptosis, an alternative mechanism for generating death signals. Cell, 1995, 82, 405-14.
8. Claus, R.; Russwurm, S.; Meisner, M.; Kinscherf, R.; Deigner, H.P. Modulation of the ceramide level, a novel therapeutic concept? Curr. Drug Targets, 2000, 1, 185-205.
9. Hannun, Y.A.; Obeid, L.M. Principles of bioactive lipid signalling, lessons from sphingolipids. Nat. Rev. Mol. Cell Biol., 2008, 9, 139-50.
10. van Meer, G.; Voelker, D.R.; Feigenson, G.W. Membrane lipids, where they are and how they behave. Nat. Rev. Mol. Cell Biol., 2008, 9, 112-24.
11. Raggers, R.J.; van Helvoort, A.; Evers, R.; van Meer, G. The human multidrug resistance protein MRP1 translocates sphingolipid analogs across the plasma membrane. J. Cell Sci., 1999, 112 (Pt 3), 415-22.
12. van Helvoort, A.; Giudici, M.L.; Thielemans, M.; van Meer, G. Transport of sphingomyelin to the cell surface is inhibited by brefeldin A and in mitosis, where C6-NBD-sphingomyelin is translocated across the plasma membrane by a multidrug transporter activity. J. Cell Sci., 1997, 110 (Pt 1), 75-83.
13. van Helvoort, A.; Smith, A.J.; Sprong, H.; Fritzsche, I.; Schinkel, A.H.; Borst, P.; van Meer, G. MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell, 1996, 87, 507-17.
14. Claus, R.A.; Bunck, A.C.; Bockmeyer, C.L.; Brunkhorst, F.M.; Losche, W.; Kinscherf, R.; Deigner, H.P. Role of increased sphingomyelinase activity in apoptosis and organ failure of patients with severe sepsis. FASEB J., 2005, 19, 1719-21.
15. Bettaieb, A.; Record, M.; Come, M.G.; Bras, A.C.; Chap, H.; Laurent, G.; Jaffrezou, J.P. Opposite effects of tumor necrosis factor alpha on the sphingomyelin-ceramide pathway in two myeloid leukemia cell lines, role of transverse sphingomyelin distribution in the plasma membrane. Blood, 1996, 88, 1465-72.
16. Lehne, G. P-glycoprotein as a drug target in the treatment of multidrug resistant cancer. Curr. Drug Targets, 2000, 1, 85-99.
17. Hendrich, A.B.; Michalak, K. Lipids as a target for drugs modulating multidrug resistance of cancer cells. Curr. Drug Targets, 2003, 4, 23-30.
18. Bezombes, C.; Maestre, N.; Laurent, G.; Levade, T.; Bettaieb, A.; Jaffrezou, J.P. Restoration of TNF-alpha-induced ceramide generation and apoptosis in resistant human leukemia KG1a cells by the P-glycoprotein blocker PSC833. FASEB J., 1998, 12, 101-9.
19. Santana, P.; Pena, L.A.; Haimovitz-Friedman, A.; Martin, S.; Green, D.; McLoughlin, M.; Cordon-Cardo, C.; Schuchman, E.H.; Fuks, Z.; Kolesnick, R. Acid sphingomyelinase-deficient huma lymphoblasts and mice are defective in radiation-induced apoptosis. Cell, 1996, 86, 189-99.
20. Horinouchi, K.; Erlich, S.; Perl, D.P.; Ferlinz, K.; Bisgaier, C.L.; Sandhoff, K.; Desnick, R.J.; Stewart, C.L.; Schuchman, E.H. Acid sphingomyelinase deficient mice, a model of types A and B Niemann Pick disease. Nat. Genet., 1995, 10, 288-93.
21. Qiu, H.; Edmunds, T.; Baker-Malcolm, J.; Karey, K.P.; Estes, S.; Schwarz, C.; Hughes, H.; Van Patten, S.M. Activation of human acid sphingomyelinase through modification or deletion of C-terminal cysteine. J. Biol. Chem., 2003, 278, 32744-52.
22. Tomiuk, S.; Hofmann, K.; Nix, M.; Zumbansen, M.; Stoffel, W. Cloned mammalian neutral sphingomyelinase, functions in sphin-golipid signaling? Proc. Natl. Acad. Sci. USA, 1998, 95, 3638-43.
23. Hofmann, K.; Tomiuk, S.; Wolff, G.; Stoffel, W. Cloning and characterization of the mammalian brain-specific, Mg2+-dependent neutral sphingomyelinase. Proc. Natl. Acad. Sci. USA, 2000, 97, 5895-900.
24. Yabu, T.; Imamura, S.; Yamashita, M.; Okazaki, T. Identification of Mg2+-dependent neutral sphingomyelinase 1 as a mediator of heat stress-induced ceramide generation and apoptosis. J. Biol. Chem., 2008.
25. Okazaki, T.; Bielawska, A.; Domae, N.; Bell, R.M.; Hannun, Y.A. Characteristics and partial purification of a novel cytosolic, magne-sium-independent, neutral sphingomyelinase activated in the early signal transduction of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation. J. Biol. Chem., 1994, 269, 4070-7.
26. Spence, M.W.; Byers, D.M.; Palmer, F.B.; Cook, H.W. A new Zn2+-stimulated sphingomyelinase in fetal bovine serum. J. Biol. Chem., 1989, 264, 5358-63.
27. Tabas, I. Secretory sphingomyelinase. Chem. Phys. Lipids, 1999, 102, 123-30.
28. Chan, E.C.; Chang, C.C.; Li, Y.S.; Chang, C.A.; Chiou, C.C.; Wu, T.Z. Purification and characterization of neutral sphingomyelinase from Helicobacter pylori. Biochemistry, 2000, 39, 4838-45.
29. Rose, F.; Zeller, S.A.; Chakraborty, T.; Domann, E.; Machleidt, T.; Kronke, M.; Seeger, W.; Grimminger, F.; Sibelius, U. Human endothelial cell activation and mediator release in response to Listeria monocytogenes virulence factors. Infect. Immun., 2001, 69, 897-905.
30. Utermohlen, O.; Herz, J.; Schramm, M.; Kronke, M. Fusogenicity of membranes, The impact of acid sphingomyelinase on innate immune responses. Immunobiology, 2008, 213, 307-314.
31. Marchesini, N.; Hannun, Y.A. Acid and neutral sphingomyelinases, roles and mechanisms of regulation. Biochem. Cell Biol., 2004, 82, 27-44.
32. Bollinger, C.R.; Teichgraber, V.; Gulbins, E. Ceramide-enriched membrane domains. Biochim. Biophys. Acta, 2005, 1746, 284-94.
33. Perrotta, C.; De Palma, C.; Falcone, S.; Sciorati, C.; Clementi, E. Nitric oxide, ceramide and sphingomyelinase-coupled receptors, a tale of enzymes and messengers coordinating cell death, survival and differentiation. Life Sci., 2005, 77, 1732-9.
34. Hakogi, T.; Taichi, M.; Katsumura, S. Synthesis of a nitrogen analogue of sphingomyelin as a sphingomyelinase inhibitor. Org. Lett., 2003, 5, 2801-4.
35. Hakogi, T.; Monden, Y.; Taichi, M.; Iwama, S.; Fujii, S.; Ikeda, K.; Katsumura, S. Synthesis of sphingomyelin carbon analogues as sphingomyelinase inhibitors. J. Org. Chem., 2002, 67, 4839-46.
36. Yokomatsu, T.; Takechi, H.; Akiyama, T.; Shibuya, S.; Kominato, T.; Soeda, S.; Shimeno, H. Synthesis and evaluation of a difluoromethylene analogue of sphingomyelin as an inhibitor of sphingomyelinase. Bioorg. Med. Chem. Lett., 2001, 11, 1277-80.
37. Sakata, A.; Yasuda, K.; Ochiai, T.; Shimeno, H.; Hikishima, S.; Yokomatsu, T.; Shibuya, S.; Soeda, S. Inhibition of lipopolysac-charide-induced release of interleukin-8 from intestinal epithelial cells by SMA, a novel inhibitor of sphingomyelinase and its therapeutic effect on dextran sulphate sodium-induced colitis in mice. Cell Immunol., 2007, 245, 24-31.
38. Sakata, A.; Ochiai, T.; Shimeno, H.; Hikishima, S.; Yokomatsu, T.; Shibuya, S.; Toda, A.; Eyanagi, R.; Soeda, S. Acid sphingomye-linase inhibition suppresses lipopolysaccharide-mediated release of inflammatory cytokines from macrophages and protects against disease pathology in dextran sulphate sodium-induced colitis in mice. Immunology, 2007, 122, 54-64.
39. Soeda, S.; Tsuji, Y.; Ochiai, T.; Mishima, K.; Iwasaki, K.; Fujiwara, M.; Yokomatsu, T.; Murano, T.; Shibuya, S.; Shimeno, H. Inhibition of sphingomyelinase activity helps to prevent neuron death caused by ischemic stress. Neurochem. Int., 2004, 45, 619-26.
40. Yu, Z.F.; Nikolova-Karakashian, M.; Zhou, D.; Cheng, G.; Schuchman, E.H.; Mattson, M.P. Pivotal role for acidic sphingo-myelinase in cerebral ischemia-induced ceramide and cytokine production, and neuronal apoptosis. J. Mol. Neurosci., 2000, 15, 85-97.
41. Yokomatsu, T.; Murano, T.; Akiyama, T.; Koizumi, J.; Shibuya, S.; Tsuji, Y.; Soeda, S.; Shimeno, H. Synthesis of non-competitive inhibitors of sphingomyelinases with significant activity. Bioorg. Med. Chem. Lett., 2003, 13, 229-36.
42. Lister, M.D.; Ruan, Z.S.; Bittman, R. Interaction of sphingomye-linase with sphingomyelin analogs modified at the C-1 and C-3 positions of the sphingosine backbone. Biochim. Biophys. Acta, 1995, 1256, 25-30.
43. Taguchi, M.; Goda, K.; Sugimoto, K.; Akama, T.; Yamamoto, K.; Suzuki, T.; Tomishima, Y.; Nishiguchi, M.; Arai, K.; Takahashi, K.; Kobori, T. Biological evaluation of sphingomyelin analogues as inhibitors of sphingomyelinase. Bioorg. Med. Chem. Lett., 2003, 13, 3681-4.
44. Taguchi, M.; Sugimoto, K.; Goda, K.; Akama, T.; Yamamoto, K.; Suzuki, T.; Tomishima, Y.; Nishiguchi, M.; Arai, K.; Takahashi, K.; Kobori, T. Sphingomyelin analogues as inhibitors of sphingomyelinase. Bioorg. Med. Chem. Lett., 2003, 13, 1963-6.
45. Arenz, C.; Thutewohl, M.; Block, O.; Waldmann, H.; Altenbach, H.J.; Giannis, A. Manumycin A and its analogues are irreversible inhibitors of neutral sphingomyelinase. Chembiochem, 2001, 2, 141-3.
46. Nara, F.; Tanaka, M.; Hosoya, T.; Suzuki-Konagai, K.; Ogita, T. Scyphostatin, a neutral sphingomyelinase inhibitor from a discomycete, Trichopeziza mollissima, taxonomy of the producing organism, fermentation, isolation, and physico-chemical properties. J. Antibiot. (Tokyo), 1999, 52, 525-30.
47. Nara, F.; Tanaka, M.; Masuda-Inoue, S.; Yamasato, Y.; Doi-Yoshioka, H.; Suzuki-Konagai, K.; Kumakura, S.; Ogita, T. Biological activities of scyphostatin, a neutral sphingomyelinase inhibitor from a discomycete, Trichopeziza mollissima. J. Antibiot. (Tokyo), 1999, 52, 531-5.
48. Claus, R.A.; Wustholz, A.; Muller, S.; Bockmeyer, C.L.; Riedel, N.H.; Kinscherf, R.; Deigner, H.P. Synthesis and antiapoptotic activity of a novel analogue of the neutral sphingomyelinase inhibitor scyphostatin. Chembiochem, 2005, 6, 726-37.
49. Arenz, C.; Giannis, A. Synthesis of the first selective irreversible inhibitor of neutral sphingomyelinase. Eur. J. Org. Chem., 2001, 137-140.
50. Arenz, C.; Giannis, A. Synthesis of the First Selective Irreversible Inhibitor of Neutral Sphingomyelinase Angew. Chem. Int. Ed. Engl., 2000, 39, 1440-1442.
51. Arenz, C.; Gartner, M.; Wascholowski, V.; Giannis, A. Synthesis and biochemical investigation of scyphostatin analogues as inhibitors of neutral sphingomyelinase. Bioorg. Med. Chem., 2001, 9, 2901-2904.
52. Gibbs, J.B.; Oliff, A.; Kohl, N.E. Farnesyltransferase inhibitors, Ras research yields a potential cancer therapeutic. Cell, 1994, 77, 175-8.
53. Liu, B.; Andrieu-Abadie, N.; Levade, T.; Zhang, P.; Obeid, L.M.; Hannun, Y.A. Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death. J. Biol. Chem., 1998, 273, 11313-20.
54. Liu, B.; Hannun, Y.A. Inhibition of the neutral magnesium-dependent sphingomyelinase by glutathione. J. Biol. Chem., 1997, 272, 16281-7.
55. Wascholowski, V.; Giannis, A. Sphingolactones, selective and irreversible inhibitors of neutral sphingomyelinase. Angew. Chem. Int. Ed. Engl., 2006, 45, 827-30.
56. Amtmann, E.; Baader, W.; Zoller, M. Neutral sphingomyelinase inhibitor C11AG prevents lipopolysaccharide-induced macrophage activation. Drugs Exp. Clin. Res., 2003, 29, 5-13.
57. Amtmann, E.; Zoller, M. Stimulation of CD95-induced apoptosis in T-cells by a subtype specific neutral sphingomyelinase inhibitor. Biochem. Pharmacol., 2005, 69, 1141-8.
58. Luberto, C.; Hassler, D.F.; Signorelli, P.; Okamoto, Y.; Sawai, H.; Boros, E.; Hazen-Martin, D.J.; Obeid, L.M.; Hannun, Y.A.; Smith, G.K. Inhibition of tumor necrosis factor-induced cell death in MCF7 by a novel inhibitor of neutral sphingomyelinase. J. Biol. Chem., 2002, 277, 41128-41139.
59. Marchesini, N.; Luberto, C.; Hannun, Y.A. Biochemical properties of mammalian neutral sphingomyelinase 2 and its role in sphingolipid metabolism. J. Biol. Chem., 2003, 278, 13775-83
60. Trajkovic, K.; Hsu, C.; Chiantia, S.; Rajendran, L.; Wenzel, D.; Wieland, F.; Schwille, P.; Brugger, B.; Simons, M. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science, 2008, 319, 1244-7.
61. Nakagawa, Y.; Iinuma, M.; Naoe, T.; Nozawa, Y.; Akao, Y. Characterized mechanism of alpha-mangostin-induced cell death, caspase-independent apoptosis with release of endonuclease-G from mitochondria and increased miR-143 expression in human colorectal cancer DLD-1 cells. Bioorg. Med. Chem., 2007, 15, 5620-8.
62. Hamada, M.; Iikubo, K.; Ishikawa, Y.; Ikeda, A.; Umezawa, K.; Nishiyama, S. Biological activities of alpha-mangostin derivatives against acidic sphingomyelinase. Bioorg. Med. Chem. Lett., 2003, 13, 3151-3.
63. Okudaira, C.; Ikeda, Y.; Kondo, S.; Furuya, S.; Hirabayashi, Y.; Koyano, T.; Saito, Y.; Umezawa, K. Inhibition of acidic sphingomyelinase by xanthone compounds isolated from Garcinia speciosa. J. Enzyme. Inhib., 2000, 15, 129-38.
64. Kolzer, M.; Arenz, C.; Ferlinz, K.; Werth, N.; Schulze, H.; Klingenstein, R.; Sandhoff, K. Phosphatidylinositol-3,5-Bisphosphate is a potent and selective inhibitor of acid sphingomyelinase. Biol. Chem., 2003, 384, 1293-8.
65. Testai, F.D.; Landek, M.A.; Goswami, R.; Ahmed, M.; Dawson, G. Acid sphingomyelinase and inhibition by phosphate ion, role of inhibition by phosphatidyl-myo-inositol 3,4,5-triphosphate in oligodendrocyte cell signaling. J. Neurochem., 2004, 89, 636-44.
66. Gomez-Munoz, A. Ceramide-1-phosphate, a novel regulator of cell activation. FEBS Lett., 2004, 562, 5-10.
67. Gomez-Munoz, A.; Kong, J.; Salh, B.; Steinbrecher, U.P. Sphingosine-1-phosphate inhibits acid sphingomyelinase and blocks apoptosis in macrophages. FEBS Lett., 2003, 539, 56-60.
68. Gomez-Munoz, A.; Kong, J.Y.; Salh, B.; Steinbrecher, U.P. Ceramide-1-phosphate blocks apoptosis through inhibition of acid sphingomyelinase in macrophages. J. Lipid Res., 2004, 45, 99-105.
69. Sakuragawa, N.; Sakuragaw, M.; Kuwabara, T.; Pentchev, P.G.; Barranger, J.A.; Brady, R.O. Niemann-Pick disease experimental model, sphingomyelinase reduction induced by AY-9944. Science, 1977, 196, 317-9.
70. Albouz, S.; Hauw, J.J.; Berwald-Netter, Y.; Boutry, J.M.; Bourdon, R.; Baumann, N. Tricyclic antidepressants induce sphingomyelinase deficiency in fibroblast and neuroblastoma cell cultures. Biomedicine, 1981, 35, 218-20.
71. Albouz, S.; Vanier, M.T.; Hauw, J.J.; Le Saux, F.; Boutry, J.M.; Baumann, N. Effect of tricyclic antidepressants on sphingomyelinase and other sphingolipid hydrolases in C6 cultured glioma cells. Neurosci. Lett., 1983, 36, 311-5.
72. Yoshida, Y.; Arimoto, K.; Sato, M.; Sakuragawa, N.; Arima, M.; Satoyoshi, E. Reduction of acid sphingomyelinase activity in human fibroblasts induced by AY-9944 and other cationic amphiphilic drugs. J. Biochem., 1985, 98, 1669-79.
73. Michalak, K.; Wesolowska, O.; Motohashi, N.; Molnar, J.; Hendrich, A.B. Interactions of phenothiazines with lipid bilayer and their role in multidrug resistance reversal. Curr. Drug Targets, 2006, 7, 1095-105.
74. Kolzer, M.; Werth, N.; Sandhoff, K. Interactions of acid sphingomye-linase and lipid bilayers in the presence of the tricyclic antidepressant desipramine. FEBS Lett., 2004, 559, 96-8.
75. Hurwitz, R.; Ferlinz, K.; Sandhoff, K. The tricyclic antidepressant desipramine causes proteolytic degradation of lysosomal sphingomyelinase in human fibroblasts. Biol. Chem. Hoppe Seyler, 1994, 375, 447-50.
76. de Duve, C.; de Barsy, T.; Poole, B.; Trouet, A.; Tulkens, P.; Van Hoof, F. Commentary. Lysosomotropic agents. Biochem. Pharmacol., 1974, 23, 2495-531.
77. Gregoriadis, G. The carrier potential of liposomes in biology and medicine (second of two parts). N. Engl. J. Med., 1976, 295, 765-70.
78. Kornhuber, J.; Tripal, P.; Reichel, M.; Terfloth, L.; Bleich, S.; Wiltfang, J.; Gulbins, E. Identification of new functional inhibitors of acid sphingomyelinase using a structure-property-activity relation model. J. Med. Chem., 2008, 51, 219-37.
79. Saldeen, J.; Jaffrezou, J.P.; Welsh, N. The acid sphingomyelinase inhibitor SR33557 counteracts TNF-alpha-mediated potentiation of IL-1beta-induced NF-kappaB activation in the insulin-producing cell line Rinm5F. Autoimmunity, 2000, 32, 241-54.
80. Higuchi, M.; Singh, S.; Jaffrezou, J.P.; Aggarwal, B.B. Acidic sphingomyelinase-generated ceramide is needed but not sufficient for TNF-induced apoptosis and nuclear factor-kappa B activation. J. Immunol., 1996, 157, 297-304.
81. Bhatia, R.; Matsushita, K.; Yamakuchi, M.; Morrell, C.N.; Cao, W.; Lowenstein, C.J. Ceramide triggers Weibel-Palade body exocytosis. Circ. Res., 2004, 95, 319-24.
82. Hundal, R.S.; Gomez-Munoz, A.; Kong, J.Y.; Salh, B.S.; Marotta, A.; Duronio, V.; Steinbrecher, U.P. Oxidized low density lipoprotein inhibits macrophage apoptosis by blocking ceramide generation, thereby maintaining protein kinase B activation and Bcl-XL levels. J. Biol. Chem., 2003, 278, 24399-408.
83. Zhang, D.X.; Yi, F.X.; Zou, A.P.; Li, P.L. Role of ceramide in TNF-alpha-induced impairment of endothelium-dependent vasorelaxation in coronary arteries. Am. J. Physiol. Heart Circ. Physiol., 2002, 283, H1785-94.
84. Corda, S.; Laplace, C.; Vicaut, E.; Duranteau, J. Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide. Am. J. Respir. Cell Mol. Biol., 2001, 24, 762-8.
85. Liu, X.; Zeidan, Y.H.; Elojeimy, S.; Holman, D.H.; El-Zawahry, A.M.; Guo, G.W.; Bielawska, A.; Bielawski, J.; Szulc, Z.; Rubinchik, S.; Dong, J.Y.; Keane, T.E.; Tavassoli, M.; Hannun, Y.A.; Norris, J.S. Involvement of sphingolipids in apoptin-induced cell killing. Mol. Ther., 2006, 14, 627-36.
86. Kornhuber, J.; Medlin, A.; Bleich, S.; Jendrossek, V.; Henkel, A.W.; Wiltfang, J.; Gulbins, E. High activity of acid sphingomyelinase in major depression. J. Neural. Transm., 2005, 112, 1583-90.
87. Elojeimy, S.; Holman, D.H.; Liu, X.; El-Zawahry, A.; Villani, M.; Cheng, J.C.; Mahdy, A.; Zeidan, Y.; Bielwaska, A.; Hannun, Y.A.; Norris, J.S. New insights on the use of desipramine as an inhibitor for acid ceramidase. FEBS Lett., 2006, 580, 4751-6.
88. Loidl, A.; Sevcsik, E.; Riesenhuber, G.; Deigner, H.P.; Hermetter, A. Oxidized phospholipids in minimally modified low density lipoprotein induce apoptotic signaling via activation of acid sphingomyelinase in arterial smooth muscle cells. J. Biol. Chem., 2003, 278, 32921-8.
89. Deigner, H.P.; Claus, R.; Bonaterra, G.A.; Gehrke, C.; Bibak, N.; Blaess, M.; Cantz, M.; Metz, J.; Kinscherf, R. Ceramide induces aSMase expression, implications for oxLDL-induced apoptosis. FASEB J., 2001, 15, 807-14.
90. Loidl, A.; Claus, R.; Ingolic, E.; Deigner, H.P.; Hermetter, A. Role of ceramide in activation of stress-associated MAP kinases by minimally modified LDL in vascular smooth muscle cells. Biochim. Biophys. Acta, 2004, 1690, 150-8.
91. Deigner, H.P.; Hermetter, A. Oxidized phospholipids, emerging lipid mediators in pathophysiology. Curr. Opin. Lipidol., 2008, 19, 289-94.
92. Kok, J.W.; Sietsma, H. Sphingolipid metabolism enzymes as targets for anticancer therapy. Curr. Drug Targets, 2004, 5, 375-82.
93. Herr, I.; Wilhelm, D.; Bohler, T.; Angel, P.; Debatin, K.M. Activation of CD95 (APO-1/Fas) signaling by ceramide mediates cancer therapy-induced apoptosis. EMBO J., 1997, 16, 6200-8.
94. Bonhoure, E.; Pchejetski, D.; Aouali, N.; Morjani, H.; Levade, T.; Kohama, T.; Cuvillier, O. Overcoming MDR-associated chemoresistance in HL-60 acute myeloid leukemia cells by targeting sphingosine kinase-1. Leukemia, 2006, 20, 95-102.
95. Perry, D.K.; Carton, J.; Shah, A.K.; Meredith, F.; Uhlinger, D.J.; Hannun, Y.A. Serine palmitoyltransferase regulates de novo ceramide generation during etoposide-induced apoptosis. J. Biol. Chem., 2000, 275, 9078-84.
96. Bruno, A.P.; Laurent, G.; Averbeck, D.; Demur, C.; Bonnet, J.; Bettaieb, A.; Levade, T.; Jaffrezou, J.P. Lack of ceramide generation in TF-1 human myeloid leukemic cells resistant to ionizing radiation. Cell Death Differ., 1998, 5, 172-82.
97. Jarvis, W.D.; Fornari, F.A., Jr.; Browning, J.L.; Gewirtz, D.A.; Kolesnick, R.N.; Grant, S. Attenuation of ceramide-induced apoptosis by diglyceride in human myeloid leukemia cells. J. Biol. Chem., 1994, 269, 31685-92.
98. Obeid, L.M.; Linardic, C.M.; Karolak, L.A.; Hannun, Y.A. Programmed cell death induced by ceramide. Science, 1993, 259, 1769-71.
99. Okazaki, T.; Bell, R.M.; Hannun, Y.A. Sphingomyelin turnover induced by vitamin D3 in HL-60 cells. Role in cell differentiation. J. Biol. Chem., 1989, 264, 19076-80.
100. Dbaibo, G.S.; El-Assaad, W.; Krikorian, A.; Liu, B.; Diab, K.; Idriss, N.Z.; El-Sabban, M.; Driscoll, T.A.; Perry, D.K.; Hannun, Y.A. Ceramide generation by two distinct pathways in tumor necrosis factor alpha-induced cell death. FEBS Lett., 2001, 503, 7-12.
101. Jaffrezou, J.P.; Levade, T.; Bettaieb, A.; Andrieu, N.; Bezombes, C.; Maestre, N.; Vermeersch, S.; Rousse, A.; Laurent, G. Daunorubicin-induced apoptosis, triggering of ceramide generation through sphingomyelin hydrolysis. EMBO J., 1996, 15, 2417-24.
102. Andrieu-Abadie, N.; Gouaze, V.; Salvayre, R.; Levade, T. Ceramide in apoptosis signaling, relationship with oxidative stress. Free Radic. Biol. Med., 2001, 31, 717-28.
103. Quillet-Mary, A.; Jaffrezou, J.P.; Mansat, V.; Bordier, C.; Naval, J.; Laurent, G. Implication of mitochondrial hydrogen peroxide generation in ceramide-induced apoptosis. J. Biol. Chem., 1997, 272, 21388-95.
104. Phillips, D.C.; Allen, K.; Griffiths, H.R. Synthetic ceramides induce growth arrest or apoptosis by altering cellular redox status. Arch. Biochem. Biophys., 2002, 407, 15-24.
105. Nishizuka, Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science, 1992, 258, 607-14.
106. Sawai, H.; Okazaki, T.; Takeda, Y.; Tashima, M.; Sawada, H.; Okuma, M.; Kishi, S.; Umehara, H.; Domae, N. Ceramide-induced translocation of protein kinase C-delta and -epsilon to the cytosol. Implications in apoptosis. J. Biol. Chem., 1997, 272, 2452-8.
107. Sawai, H.; Okazaki, T.; Yamamoto, H.; Okano, H.; Takeda, Y.; Tashima, M.; Sawada, H.; Okuma, M.; Ishikura, H.; Umehara, H.; et al. Requirement of AP-1 for ceramide-induced apoptosis in human leukemia HL-60 cells. J. Biol. Chem., 1995, 270, 27326-31.
108. Schissel, S.L.; Keesler, G.A.; Schuchman, E.H.; Williams, K.J.; Tabas, I. The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene. J. Biol. Chem., 1998, 273, 18250-9.
109. Schissel, S.L.; Jiang, X.; Tweedie-Hardman, J.; Jeong, T.; Camejo, E.H.; Najib, J.; Rapp, J.H.; Williams, K.J.; Tabas, I. Secretory sphingomyelinase, a product of the acid sphingomyelinase gene, can hydrolyze atherogenic lipoproteins at neutral pH. Implications for atherosclerotic lesion development. J. Biol. Chem., 1998, 273, 2738-6.
110. Schissel, S.L.; Schuchman, E.H.; Williams, K.J.; Tabas, I. Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene. J. Biol. Chem., 1996, 271, 18431-6.
111. Marcusson, E.G.; Horazdovsky, B.F.; Cereghino, J.L.; Gharakhanian, E.; Emr, S.D. The sorting receptor for yeast vacuolar carboxypeptidase Y is encoded by the VPS10 gene. Cell, 1994, 77, 579-86
112. Dhami, R.; Schuchman, E.H. Mannose 6-phosphate receptor-mediated uptake is defective in acid sphingomyelinase-deficient macrophages, implications for Niemann-Pick disease enzyme replacement therapy. J. Biol. Chem., 2004, 279, 1526-32.
113. Ni, X.; Morales, C.R. The lysosomal trafficking of acid sphingomyelinase is mediated by sortilin and mannose 6-phosphate receptor. Traffic, 2006, 7, 889-902.
114. Takahashi, I.; Takahashi, T.; Mikami, T.; Komatsu, M.; Ohura, T.; Schuchman, E.H.; Takada, G. Acid sphingomyelinase, relation of 93lysine residue on the ratio of intracellular to secreted enzyme activity. Tohoku J. Exp. Med., 2005, 206, 333-40.
115. Zeidan, Y.H.; Hannun, Y.A. Activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation. J. Biol. Chem., 2007, 282, 11549-61.
116. Teichgraber, V.; Ulrich, M.; Endlich, N.; Riethmuller, J.; Wilker, B.; De Oliveira-Munding, C.C.; van Heeckeren, A.M.; Barr, M.L.; von Kurthy, G.; Schmid, K.W.; Weller, M.; Tummler, B.; Lang, F.; Grassme, H.; Doring, G.; Gulbins, E. Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat. Med., 2008, 14, 382-91.
117. Goggel, R.; Winoto-Morbach, S.; Vielhaber, G.; Imai, Y.; Lindner, K.; Brade, L.; Brade, H.; Ehlers, S.; Slutsky, A.S.; Schutze, S.; Gulbins, E.; Uhlig, S. PAF-mediated pulmonary edema, a new role for acid sphingomyelinase and ceramide. Nat. Med., 2004, 10, 155-60.
118. von Bismarck, P.; Klemm, K.; Wistadt, C.F.; Winoto-Morbach, S.; Uhlig, U.; Schutze, S.; Uhlig, S.; Lachmann, B.; Krause, M.F. Surfactant "fortification" by topical inhibition of nuclear factor-kappaB activity in a newborn piglet lavage model. Crit. Care Med., 2007, 35, 2309-18.
119. Loidl, A.; Claus, R.; Deigner, H.P.; Hermetter, A. High-precision fluorescence assay for sphingomyelinase activity of isolated enzymes and cell lysates. J. Lipid Res., 2002, 43, 815-23.
120. Lang, P.A.; Schenck, M.; Nicolay, J.P.; Becker, J.U.; Kempe, D.S.; Lupescu, A.; Koka, S.; Eisele, K.; Klarl, B.A.; Rubben, H.; Schmid, K.W.; Mann, K.; Hildenbrand, S.; Hefter, H.; Huber, S.M.; Wieder, T.; Erhardt, A.; Haussinger, D.; Gulbins, E.; Lang, F. Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide. Nat. Med., 2007, 13, 164-70.
121. Mari, M.; Fernandez-Checa, J.C. Sphingolipid signalling and liver diseases. Liver International, 2007, 27, 440-450
122. Ogretmen, B.; Hannun, Y.A. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat. Rev. Cancer, 2004, 4, 604-16.
123. Llacuna, L.; Mari, M.; Garcia-Ruiz, C.; Fernandez-Checa, J.C.; Morales, A. Critical role of acidic sphingomyelinase in murine hepatic ischemia-reperfusion injury. Hepatology, 2006, 44, 561-72.
124. Aggarwal, B.B.; Shishodia, S.; Ashikawa, K.; Bharti, A.C. The role of TNF and its family members in inflammation and cancer, lessons from gene deletion. Curr. Drug Targets Inflamm. Allergy, 2002, 1, 327-41.
125. Friedrichs, G.S.; Swillo, R.E.; Jow, B.; Bridal, T.; Numann, R.; Warner, L.M.; Killar, L.M.; Sidek, K. Sphingosine modulates myocyte electrophysiology, induces negative inotropy, and decreases survival after myocardial ischemia. J. Cardiovasc. Pharmacol., 2002, 39, 18-28.
126. Sharma, C.; Smith, T.; Li, S.; Schroepfer, G.J., Jr.; Needleman, D.H. Inhibition of Ca2+ release channel (ryanodine receptor) activity by sphingolipid bases, mechanism of action. Chem. Phys. Lipids, 2000, 104, 1-11.
127. Schreur, K.D.; Liu, S. Involvement of ceramide in inhibitory effect of IL-1 beta on L-type Ca2+ current in adult rat ventricular myocytes. Am. J. Physiol., 1997, 272, H2591-8.
128. Oral, H.; Dorn, G.W., 2nd; Mann, D.L. Sphingosine mediates the immediate negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian cardiac myocyte. J. Biol. Chem., 1997, 272, 4836-42.
129. Torre-Amione, G.; Kapadia, S.; Lee, J.; Bies, R.D.; Lebovitz, R.; Mann, D.L. Expression and functional significance of tumor necrosis factor receptors in human myocardium. Circulation, 1995, 92, 1487-93.
130. Hofmann, U.; Domeier, E.; Frantz, S.; Laser, M.; Weckler, B.; Kuhlencordt, P.; Heuer, S.; Keweloh, B.; Ertl, G.; Bonz, A.W. Increased myocardial oxygen consumption by TNF-alpha is mediated by a sphingosine signaling pathway. Am. J. Physiol. Heart Circ. Physiol., 2003, 284, H2100-5.
131. Stamm, C.; Cowan, D.B.; Friehs, I.; Noria, S.; del Nido, P.J.; McGowan, F.X., Jr. Rapid endotoxin-induced alterations in myocardial calcium handling, obligatory role of cardiac TNF-alpha. Anesthesiology, 2001, 95, 1396-405.
132. Cowan, D.B.; Noria, S.; Stamm, C.; Garcia, L.M.; Poutias, D.N.; del Nido, P.J.; McGowan, F.X., Jr. Lipopolysaccharide internalization activates endotoxin-dependent signal transduction in cardiomyocytes. Circ. Res., 2001, 88, 491-8.
133. Edmunds, N.J.; Woodward, B. Effects of tumour necrosis factor-alpha on the coronary circulation of the rat isolated perfused heart, a potential role for thromboxane A2 and sphingosine. Br. J. Pharmacol., 1998, 124, 493-8.
134. Kolesnick, R. The therapeutic potential of modulating the ceramide/ sphingomyelin pathway. J. Clin. Invest., 2002, 110, 3-8.
135. Cailleret, M.; Amadou, A.; Andrieu-Abadie, N.; Nawrocki, A.; Adamy, C.; Ait-Mamar, B.; Rocaries, F.; Best-Belpomme, M.; Levade, T.; Pavoine, C.; Pecker, F. N-acetylcysteine prevents the deleterious effect of tumor necrosis factor-(alpha) on calcium transients and contraction in adult rat cardiomyocytes. Circulation, 2004, 109, 406-11.
136. Amadou, A.; Nawrocki, A.; Best-Belpomme, M.; Pavoine, C.; Pecker, F. Arachidonic acid mediates dual effect of TNF-alpha on Ca2+ transients and contraction of adult rat cardiomyocytes. Am. J. Physiol. Cell Physiol., 2002, 282, C1339-47.
137. Jayadev, S.; Linardic, C.M.; Hannun, Y.A. Identification of arachidonic acid as a mediator of sphingomyelin hydrolysis in response to tumor necrosis factor alpha. J. Biol. Chem., 1994, 269, 5757-63.
138. Robinson, B.S.; Hii, C.S.; Poulos, A.; Ferrante, A. Activation of neutral sphingomyelinase in human neutrophils by polyunsaturated fatty acids. Immunology, 1997, 91, 274-80.
139. Mazurais, D.; Robert, P.; Gout, B.; Berrebi-Bertrand, I.; Laville, M.P.; Calmels, T. Cell type-specific localization of human cardiac S1P receptors. J. Histochem. Cytochem., 2002, 50, 661-70.
140. Josephs, M.; Katan, M.; Rodrigues-Lima, F. Irreversible inactivation of magnesium-dependent neutral sphingomyelinase 1 (NSM1) by peroxynitrite, a nitric oxide-derived oxidant. FEBS Lett., 2002, 531, 329-34.
141. Castillo, S.S.; Levy, M.; Thaikoottathil, J.V.; Goldkorn, T. Reactive nitrogen and oxygen species activate different sphingomye-linases to induce apoptosis in airway epithelial cells. Exp. Cell Res., 2007, 313, 2680-6.
142. Levy, M.; Castillo, S.S.; Goldkorn, T. nSMase2 activation and trafficking are modulated by oxidative stress to induce apoptosis. Biochem. Biophys. Res. Commun., 2006, 344, 900-5.
143. Platt, F.M.; Jeyakumar, M. Substrate reduction therapy. Acta. Paediatr. Suppl., 2008, 97, 88-93.
144. Passini, M.A.; Bu, J.; Fidler, J.A.; Ziegler, R.J.; Foley, J.W.; Dodge, J.C.; Yang, W.W.; Clarke, J.; Taksir, T.V.; Griffiths, D.A.; Zhao, M.A.; O'Riordan, C.R.; Schuchman, E.H.; Shihabuddin, L.S.; Cheng, S.H. Combination brain and systemic injections of AAV provide maximal functional and survival benefits in the Niemann-Pick mouse. Proc. Natl. Acad. Sci. USA, 2007, 104, 9505-10.
145. Miranda, S.R.; He, X.; Simonaro, C.M.; Gatt, S.; Dagan, A.; Desnick, R.J.; Schuchman, E.H. Infusion of recombinant human acid sphingomyelinase into niemann-pick disease mice leads to visceral, but not neurological, correction of the pathophysiology. FASEB J., 2000, 14, 1988-95.
146. Elleder, M.; Cihula, J. Niemann-Pick disease (variation in the sphingomyelinase deficient group). Neurovisceral phenotype (A) with an abnormally protracted clinical course and variable expression of neurological symptomatology in three siblings. Eur. J. Pediatr., 1983, 140, 323-8.
147. Wilcox, W.R.; Banikazemi, M.; Guffon, N.; Waldek, S.; Lee, P.; Linthorst, G.E.; Desnick, R.J.; Germain, D.P. Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am. J. Hum. Genet., 2004, 75, 65-74.
148. Wraith, J.E.; Clarke, L.A.; Beck, M.; Kolodny, E.H.; Pastores, G.M.; Muenzer, J.; Rapoport, D.M.; Berger, K.I.; Swiedler, S.J.; Kakkis, E.D.; Braakman, T.; Chadbourne, E.; Walton-Bowen, K.; Cox, G.F. Enzyme replacement therapy for mucopolysaccharidosis I, a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J. Pediatr., 2004, 144, 581-8.
149. Weinreb, N.J.; Charrow, J.; Andersson, H.C.; Kaplan, P.; Kolodny, E.H.; Mistry, P.; Pastores, G.; Rosenbloom, B.E.; Scott, C.R.; Wappner, R.S.; Zimran, A. Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment, a report from the Gaucher Registry. Am. J. Med., 2002, 113, 112-9.
150. Sun, B.; Bird, A.; Young, S.P.; Kishnani, P.S.; Chen, Y.T.; Koeberl, D.D. Enhanced response to enzyme replacement therapy in Pompe disease after the induction of immune tolerance. Am. J. Hum. Genet., 2007, 81, 1042-9.
151. Wang, L.Y.; Ross, A.K.; Li, J.S.; Dearmey, S.M.; Mackey, J.F.; Worden,
152. Bernardo, K.; Krut, O.; Wiegmann, K.; Kreder, D.; Micheli, M.; Schafer, R.; Sickman, A.; Schmidt, W.E.; Schroder, J.M.; Meyer, H.E.; Sandhoff, K.; Kronke, M. Purification and characterization of a magnesium-dependent neutral sphingomyelinase from bovine brain. J. Biol. Chem., 2000, 275, 7641-7.
153. Itoh, M.; Kitano, T.; Watanabe, M.; Kondo, T.; Yabu, T.; Taguchi, Y.; Iwai, K.; Tashima, M.; Uchiyama, T.; Okazaki, T. Possible role of ceramide as an indicator of chemoresistance, decrease of the ceramide content via activation of glucosylceramide synthase and sphingomyelin synthase in chemoresistant leukemia. Clin. Cancer Res., 2003, 9, 415-23.
154. Liu, Y.Y.; Han, T.Y.; Giuliano, A.E.; Cabot, M.C. Ceramide glycosylation potentiates cellular multidrug resistance. FASEB J., 2001, 15, 719-30.
155. Steingart, A.B.; Cotterchio, M. Do antidepressants cause, promote, or inhibit cancers? J. Clin. Epidemiol., 1995, 48, 1407-12.
156. Daniel, W.A.; Bickel, M.H.; Honegger, U.E. The contribution of lysosomal trapping in the uptake of desipramine and chloroquine by different tissues. Pharmacol. Toxicol., 1995, 77, 402-6.
157. Cotterchio, M.; Kreiger, N.; Darlington, G.; Steingart, A. Antidepressant medication use and breast cancer risk. Am. J. Epidemiol., 2000, 151, 951-7.
158. Steingart, A.; Cotterchio, M.; Kreiger, N.; Sloan, M. Antidepressant medication use and breast cancer risk, a case-control study. Int. J. Epidemiol., 2003, 32, 961-6.
159. Gillman, P.K. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br. J. Pharmacol., 2007, 151, 737-48.
160. Pacher, P.; Kecskemeti, V. Cardiovascular side effects of new antidepressants and antipsychotics, new drugs, old concerns? Curr. Pharm. Des., 2004, 10, 2463-75.
161. Flierl, M.A.; Rittirsch, D.; Huber-Lang, M.S.; Sarma, J.V.; Ward, P.A. Molecular events in the cardiomyopathy of sepsis. Mol. Med., 2008, 14, 327-36.
162. Doehner, W.; Bunck, A.C.; Rauchhaus, M.; von Haehling, S.; Brunkhorst, F.M.; Cicoira, M.; Tschope, C.; Ponikowski, P.; Claus, R.A.; Anker, S.D. Secretory sphingomyelinase is upregulated in chronic heart failure, a second messenger system of immune activation relates to body composition, muscular functional capacity, and peripheral blood flow. Eur. Heart J., 2007, 28, 821-8.
163. Roumestan, C.; Michel, A.; Bichon, F.; Portet, K.; Detoc, M.; Henriquet, C.; Jaffuel, D.; Mathieu, M. Anti-inflammatory properties of desipramine and fluoxetine. Respir. Res., 2007, 8, 35.
164. Bianchi, M.E. DAMPs, PAMPs and alarmins, all we need to know about danger. J. Leukoc. Biol., 2007, 81, 1-5.
165. Oppenheim, J.J.; Tewary, P.; de la Rosa, G.; Yang, D. Alarmins initiate host defense. Adv. Exp. Med. Biol., 2007, 601, 185-94.
166. Oppenheim, J.J.; Yang, D. Alarmins, chemotactic activators of immune responses. Curr. Opin. Immunol., 2005, 17, 359-65
167. Bourbon, N.A.; Yun, J.; Kester, M. Ceramide directly activates protein kinase C zeta to regulate a stress-activated protein kinase signaling complex. J. Biol. Chem., 2000, 275, 35617-23.
168. Galve-Roperh, I.; Haro, A.; Diaz-Laviada, I. Ceramide-induced translocation of protein kinase C zeta in primary cultures of astrocytes. FEBS Lett., 1997, 415, 271-4.
169. Muller, G.; Storz, P.; Bourteele, S.; Doppler, H.; Pfizenmaier, K.; Mischak, H.; Philipp, A.; Kaiser, C.; Kolch, W. Regulation of Raf-1 kinase by TNF via its second messenger ceramide and cross-talk with mitogenic signalling. EMBO J., 1998, 17, 732-42
170. Lozano, J.; Berra, E.; Municio, M.M.; Diaz-Meco, M.T.; Dominguez, I.; Sanz, L.; Moscat, J. Protein kinase C zeta isoform is critical for kappa B-dependent promoter activation by sphingomyelinase. J. Biol. Chem., 1994, 269, 19200-2.
171. Fyrnys, B.; Claus, R.; Wolf, G.; Deigner, H.P. Oxidized low density lipoprotein stimulates protein kinase C (PKC) activity and expression of PKC-isotypes via prostaglandin-H-synthase in P388D1 cells. Adv. Exp. Med. Biol., 1997, 407, 93-8.
172. Blobe, G.C.; Stribling, S.; Obeid, L.M.; Hannun, Y.A. Protein kinase C isoenzymes, regulation and function. Cancer Surv., 1996, 27, 213-48.
173. Mielke, K.; Herdegen, T. Fatal shift of signal transduction is an integral part of neuronal differentiation, JNKs realize TNFalpha-mediated apoptosis in neuronlike, but not naive, PC12 cells. Mol. Cell Neurosci., 2002, 20, 211-24.
174. Westwick, J.K.; Bielawska, A.E.; Dbaibo, G.; Hannun, Y.A.; Brenner, D.A. Ceramide activates the stress-activated protein kinases. J. Biol. Chem., 1995, 270, 22689-92.
175. Zhang, P.; Miller, B.S.; Rosenzweig, S.A.; Bhat, N.R. Activation of C-jun N-terminal kinase/stress-activated protein kinase in primary glial cultures. J. Neurosci. Res., 1996, 46, 114-21.
176. Susen, K.; Heumann, R.; Blochl, A. Nerve growth factor stimulates MAPK via the low affinity receptor p75(LNTR). FEBS Lett., 1999, 463, 231-4.
177. Kinscherf, R.; Claus, R.; Deigner, H.P.; Nauen, O.; Gehrke, C.; Hermetter, A.; Russwurm, S.; Daniel, V.; Hack, V.; Metz, J. Modified low density lipoprotein delivers substrate for ceramide formation and stimulates the sphingomyelin-ceramide pathway in human macrophages. FEBS Lett., 1997, 405, 55-9.
178. Deigner, H.P.; Claus, R. Stimulation of mitogen activated protein kinase by LDL and oxLDL in human U-937 macrophage-like cells. FEBS Lett., 1996, 385, 149-53.
179. Hida, H.; Nagano, S.; Takeda, M.; Soliven, B. Regulation of mitogen activated protein kinases by sphingolipid products in oligodendrocytes. J. Neurosci., 1999, 19, 7458-67.
180. Scheid, M.P.; Foltz, I.N.; Young, P.R.; Schrader, J.W.; Duronio, V. Ceramide and cyclic adenosine monophosphate (cAMP) induce cAMP response element binding protein phosphorylation via distinct signaling pathways while having opposite effects on myeloid cell survival. Blood, 1999, 93, 217-25.
181. Willaime, S.; Vanhoutte, P.; Caboche, J.; Lemaigre-Dubreuil, Y.; Mariani, J.; Brugg, B. Ceramide-induced apoptosis in cortical neurons is mediated by an increase in p38 phosphorylation and not by the decrease in ERK phosphorylation. Eur. J. Neurosci., 2001, 13, 2037-46.
182. Tavarini, S.; Colombaioni, L.; Garcia-Gil, M. Sphingomyelinase metabolites control survival and apoptotic death in SH-SY5Y neuroblastoma cells. Neurosci. Lett., 2000, 285, 185-8.
183. Prinetti, A.; Bassi, R.; Riboni, L.; Tettamanti, G. Involvement of a ceramide activated protein phosphatase in the differentiation of neuroblastoma Neuro2a cells. FEBS Lett., 1997, 414, 475-9.
184. Dobrowsky, R.T.; Kamibayashi, C.; Mumby, M.C.; Hannun, Y.A. Ceramide activates heterotrimeric protein phosphatase 2A. J. Biol. Chem., 1993, 268, 15523-30.
185. Yoshimura, S.; Banno, Y.; Nakashima, S.; Takenaka, K.; Sakai, H.; Nishimura, Y.; Sakai, N.; Shimizu, S.; Eguchi, Y.; Tsujimoto, Y.; Nozawa, Y. Ceramide formation leads to caspase-3 activation during hypoxic PC12 cell death. Inhibitory effects of Bcl-2 on cera mide formation and caspase-3 activation. J. Biol. Chem., 1998, 273, 6921-7.
186. Keane, R.W.; Srinivasan, A.; Foster, L.M.; Testa, M.P.; Ord, T.; Nonner, D.; Wang, H.G.; Reed, J.C.; Bredesen, D.E.; Kayalar, C. Activation of CPP32 during apoptosis of neurons and astrocytes. J. Neurosci. Res., 1997, 48, 168-80.
187. Colombaioni, L.; Frago, L.M.; Varela-Nieto, I.; Pesi, R.; Garcia-Gil, M. Serum deprivation increases ceramide levels and induces apoptosis in undifferentiated HN9.10e cells. Neurochem. Int., 2002, 40, 327-36.
188. Heinrich, M.; Wickel, M.; Winoto-Morbach, S.; Schneider-Brachert, W.; Weber, T.; Brunner, J.; Saftig, P.; Peters, C.; Kronke, M.; Schutze, S. Ceramide as an activator lipid of cathepsin D. Adv. Exp. Med. Biol., 2000, 477, 305-15.
189. Huwiler, A.; Johansen, B.; Skarstad, A.; Pfeilschifter, J. Ceramide binds to the CaLB domain of cytosolic phospholipase A2 and facilitates its membrane docking and arachidonic acid release. Faseb. J., 2001, 15, 7-9.
190. Mattson, M.P.; Goodman, Y.; Luo, H.; Fu, W.; Furukawa, K. 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. J. Neurosci. Res., 1997, 49, 681-97.
191. Hunot, S.; Brugg, B.; Ricard, D.; Michel, P.P.; Muriel, M.P.; Ruberg, M.; Faucheux, B.A.; Agid, Y.; Hirsch, E.C. Nuclear translocation of NF-kappaB is increased in dopaminergic neurons of patients with parkinson disease. Proc. Natl. Acad. Sci. USA, 1997, 94, 7531-6.
192. Gill, J.S.; Windebank, A.J. Ceramide initiates NFkappaB-mediated caspase activation in neuronal apoptosis. Neurobiol. Dis., 2000, 7, 448-61.
193. France-Lanord, V.; Brugg, B.; Michel, P.P.; Agid, Y.; Ruberg, M. Mitochondrial free radical signal in ceramide-dependent apoptosis, a putative mechanism for neuronal death in Parkinson's disease. J. Neurochem., 1997, 69, 1612-21.
194. Buzas, B. Regulation of nociceptin/orphanin FQ gene expression in astrocytes by ceramide. Neuroreport, 2002, 13, 1707-10.
195. Frago, L.M.; Canon, S.; de la Rosa, E.J.; Leon, Y.; Varela-Nieto, I. Programmed cell death in the developing inner ear is balanced by nerve growth factor and insulin-like growth factor I. J. Cell Sci., 2003, 116, 475-86.
196. Gomez-Munoz, A.; Kong, J.Y.; Parhar, K.; Wang, S.W.; Gangoiti, P.; Gonzalez, M.; Eivemark, S.; Salh, B.; Duronio, V.; Steinbrecher, U.P. Ceramide-1-phosphate promotes cell survival through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway. FEBS Lett., 2005, 579, 3744-50.
197. Gangoiti, P.; Granado, M.H.; Wang, S.W.; Kong, J.Y.; Steinbrecher, U.P.; Gomez-Munoz, A. Ceramide 1-phosphate stimulates macrophage proliferation through activation of the PI3-kinase/PKB, JNK and ERK1/2 pathways. Cell Signal, 2008, 20, 726-36.
198. Goetzl, E.J.; An, S. Diversity of cellular receptors and functions for the lysophospholipid growth factors lysophosphatidic acid and sphingosine 1-phosphate. FASEB J., 1998, 12, 1589-98.
199. Pettus, B.J.; Bielawski, J.; Porcelli, A.M.; Reames, D.L.; Johnson, K.R.; Morrow, J.; Chalfant, C.E.; Obeid, L.M.; Hannun, Y.A. The sphingosine kinase 1/sphingosine-1-phosphate pathway mediates COX-2 induction and PGE2 production in response to TNF-alpha. FASEB J., 2003, 17, 1411-21.
200. Hannun, Y.A.; Bell, R.M. Regulation of protein kinase C by sphingosine and lysosphingolipids. Clin. Chim. Acta, 1989, 185, 333-45.
201. Hannun, Y.A.; Loomis, C.R.; Merrill, A.H., Jr.; Bell, R.M. Sphingosine inhibition of protein kinase C activity and of phorbol dibutyrate binding in vitro and in human platelets. J. Biol. Chem., 1986, 261, 12604-9.
202. King, C.C.; Zenke, F.T.; Dawson, P.E.; Dutil, E.M.; Newton, A.C.; Hemmings, B.A.; Bokoch, G.M. Sphingosine is a novel activator of 3-phosphoinositide-dependent kinase 1. J. Biol. Chem., 2000, 275, 18108-13.
203. Jarvis, W.D.; Fornari, F.A., Jr.; Auer, K.L.; Freemerman, A.J.; Szabo, E.; Birrer, M.J.; Johnson, C.R.; Barbour, S.E.; Dent, P.; Grant, S. Coordinate regulation of stress- and mitogen-activated protein kinases in the apoptotic actions of ceramide and sphingosine. Mol. Pharmacol., 1997, 52, 935-47.
204. Ohta, H.; Sweeney, E.A.; Masamune, A.; Yatomi, Y.; Hakomori, S.; Igarashi, Y. Induction of apoptosis by sphingosine in human leukemic HL-60 cells, a possible endogenous modulator of apoptotic DNA fragmentation occurring during phorbol ester-induced differentiation. Cancer Res., 1995, 55, 691-7.
205. Pettus, B.J.; Bielawska, A.; Spiegel, S.; Roddy, P.; Hannun, Y.A.; Chalfant, C.E. Ceramide kinase mediates cytokine- and calcium ionophore-induced arachidonic acid release. J. Biol. Chem., 2003, 278, 38206-13.
206. Harada, J.; Foley, M.; Moskowitz, M.A.; Waeber, C. Sphingosine-1-phosphate induces proliferation and morphological changes of neural progenitor cells. J. Neurochem., 2004, 88, 1026-39.
207. Pebay, A.; Toutant, M.; Premont, J.; Calvo, C.F.; Venance, L.; Cordier, J.; Glowinski, J.; Tence, M. Sphingosine-1-phosphate induces proliferation of astrocytes, regulation by intracellular signalling cascades. Eur. J. Neurosci., 2001, 13, 2067-76
208. Banno, Y.; Takuwa, Y.; Akao, Y.; Okamoto, H.; Osawa, Y.; Naganawa, T.; Nakashima, S.; Suh, P.G.; Nozawa, Y. Involvement of phospholipase D in sphingosine 1-phosphate-induced activation of phosphatidylinositol 3-kinase and Akt in Chinese hamster ovary cells overexpressing EDG3. J. Biol. Chem., 2001, 276, 35622-8.
209. Ogretmen, B.; Pettus, B.J.; Rossi, M.J.; Wood, R.; Usta, J.; Szulc, Z.; Bielawska, A.; Obeid, L.M.; Hannun, Y.A. Biochemical mechanisms of the generation of endogenous long chain ceramide in response to exogenous short chain ceramide in the A549 human lung adenocarcinoma cell line. Role for endogenous ceramide in mediating the action of exogenous ceramide. J. Biol. Chem., 2002, 277, 12960-9.
210. Xia, P.; Wang, L.; Moretti, P.A.; Albanese, N.; Chai, F.; Pitson, S.M.; D'Andrea, R.J.; Gamble, J.R.; Vadas, M.A. Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling. J. Biol. Chem., 2002, 277, 7996-8003.
211. Siehler, S.; Wang, Y.; Fan, X.; Windh, R.T.; Manning, D.R. Sphingosine 1-phosphate activates nuclear factor-kappa B through Edg receptors. Activation through Edg-3 and Edg-5, but not Edg-1, in human embryonic kidney 293 cells. J. Biol. Chem., 2001, 276, 48733-9.
212. Schuchman, E.H.; Suchi, M.; Takahashi, T.; Sandhoff, K.; Desnick, R.J. Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs. J. Biol. Chem., 1991, 266, 8531-9.
213. Schuchman, E.H.; Levran, O.; Pereira, L.V.; Desnick, R.J. Structural organization and complete nucleotide sequence of the gene encoding human acid sphingomyelinase (SMPD1). Genomics, 1992, 12, 197-205.
214. Ferlinz, K.; Hurwitz, R.; Vielhaber, G.; Suzuki, K.; Sandhoff, K. Occurrence of two molecular forms of human acid sphingomyelinase. Biochem. J., 1994, 301 (Pt 3), 855-62.
215. Wong, M.L.; Xie, B.; Beatini, N.; Phu, P.; Marathe, S.; Johns, A.; Gold, P.W.; Hirsch, E.; Williams, K.J.; Licinio, J.; Tabas, I. Acute systemic inflammation up-regulates secretory sphingomyelinase in vivo, a possible link between inflammatory cytokines and atherogenesis. Proc. Natl. Acad. Sci. USA, 2000, 97, 8681-6.
216. Marathe, S.; Kuriakose, G.; Williams, K.J.; Tabas, I. Sphingomyelinase, an enzyme implicated in atherogenesis, is present in atherosclerotic lesions and binds to specific components of the subendothelial extracellular matrix. Arterioscler Thromb. Vasc. Biol., 1999, 19, 2648-58.
217. Tomiuk, S.; Zumbansen, M.; Stoffel, W. Characterization and subcellular localization of murine and human magnesiumdependent neutral sphingomyelinase. J. Biol. Chem., 2000, 275, 5710-7.
218. Stoffel, W.; Jenke, B.; Block, B.; Zumbansen, M.; Koebke, J. Neutral sphingomyelinase 2 (smpd3) in the control of postnatal growth and development. Proc. Natl. Acad. Sci. USA, 2005, 102, 4554-9.
219. Stoffel, W.; Jenke, B.; Holz, B.; Binczek, E.; Gunter, R.H.; Knifka, J.; Koebke, J.; Niehoff, A. Neutral sphingomyelinase (SMPD3) deficiency causes a novel form of chondrodysplasia and dwarfism that is rescued by Col2A1-driven smpd3 transgene expression. Am. J. Pathol., 2007, 171, 153-61.
220. Corcoran, C.A.; He, Q.; Ponnusamy, S.; Ogretmen, B.; Huang, Y.; Sheikh, M.S. Neutral sphingomyelinase-3 is a DNA damage and nongenotoxic stress-regulated gene that is deregulated in human malignancies. Mol. Cancer Res., 2008, 6, 795-807.
221. Krut, O.; Wiegmann, K.; Kashkar, H.; Yazdanpanah, B.; Kronke, M. Novel tumor necrosis factor-responsive mammalian neutral sphingomyelinase-3 is a C-tail-anchored protein. J. Biol. Chem., 2006, 281, 13784-13793.
222. Wu, J.; Nilsson, A.; Jonsson, B.A.; Stenstad, H.; Agace, W.; Cheng, Y.; Duan, R.D. Intestinal alkaline sphingomyelinase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity. Biochem. J., 2006, 394, 299-308.
223. Duan, R.D.; Bergman, T.; Xu, N.; Wu, J.; Cheng, Y.; Duan, J.; Nelander, S.; Palmberg, C.; Nilsson, A. Identification of human intestinal alkaline sphingomyelinase as a novel ecto-enzyme related to the nucleotide phosphodiesterase family. J. Biol. Chem., 2003, 278, 38528-36.
224. Macchia, M.; Barontini, S.; Bertini, S.; Di Bussolo, V.; Fogli, S.; Giovannetti, E.; Grossi, E.; Minutolo, F.; Danesi, R. Design, synthesis, and characterization of the antitumor activity of novel ceramide analogues. J. Med. Chem., 2001, 44, 3994-4000.
225. Shikata, K.; Niiro, H.; Azuma, H.; Ogino, K.; Tachibana, T. Apoptotic activities of C2-ceramide and C2-dihydroceramide homologues against HL-60 cells. Bioorg. Med. Chem., 2003, 11, 2723-8
226. Kishida, E.; Kasahara, M.; Takagi, Y.; Matsumura, M.; Hayashi, T.; Kobayashi, S.; Masuzawa, Y. Evaluation of a trans configuration for the apoptosis-inducing activity of ceramide. J. Lipid Mediat. Cell Signal, 1997, 16, 127-37.
227. De Jonghe, S.; Van Overmeire, I.; Gunst, J.; De Bruyn, A.; Hendrix, C.; Van Calenbergh, S.; Busson, R.; De Keukeleire, D.; Philippe, J.; Herdewijn, P. Synthesis and apoptogenic activity of fluorinated ceramide and dihydroceramide analogues. Bioorg. Med. Chem. Lett., 1999, 9, 3159-64.
228. Bielawska, A.; Linardic, C.M.; Hannun, Y.A. Ceramide-mediated biology. Determination of structural and stereospecific requirements through the use of N-acyl-phenylaminoalcohol analogs. J. Biol. Chem., 1992, 267, 18493-7.
229. Wieder, T.; Geilen, C.C.; Kolter, T.; Sadeghlar, F.; Sandhoff, K.; Brossmer, R.; Ihrig, P.; Perry, D.; Orfanos, C.E.; Hannun, Y.A. Bcl-2 antagonizes apoptotic cell death induced by two new ceramide analogues. FEBS Lett., 1997, 411, 260-4.
230. Karasavvas, N.; Erukulla, R.K.; Bittman, R.; Lockshin, R.; Zakeri, Z. Stereospecific induction of apoptosis in U937 cells by N-octanoyl-sphingosine stereoisomers and N-octyl-sphingosine. The ceramide amide group is not required for apoptosis. Eur. J. Biochem., 1996, 236, 729-37.
231. Azuma, H.; Takao, R.; Shikata, K.; Niiro, H.; Tachibana, T.; Ogino, K. Synthesis and potent antileukemic activities of Nlactylsphingosine and N-lactyldihydrosphingosine. J. Med. Chem., 2003, 46, 3445-7.
232. Dagan, A.; Wang, C.; Fibach, E.; Gatt, S. Synthetic, non-natural sphingolipid analogs inhibit the biosynthesis of cellular sphingolipids, elevate ceramide and induce apoptotic cell death. Biochim. Biophys. Acta, 2003, 1633, 161-9.
233. Johnson, C.R.; Chun, J.; Bittman, R.; Jarvis, W.D. Intrinsic cytotoxicity and chemomodulatory actions of novel phenethylisothiocyanate sphingoid base derivatives in HL-60 human promyelocytic leukemia cells. J. Pharmacol. Exp. Ther., 2004, 309, 452-61.
234. Hinkovska-Galcheva, V.; Boxer, L.A.; Kindzelskii, A.; Hiraoka, M.; Abe, A.; Goparju, S.; Spiegel, S.; Petty, H.R.; Shayman, J.A. Ceramide 1-phosphate, a mediator of phagocytosis. J. Biol. Chem., 2005, 280, 26612-21.
235. van Meer, G.; Lisman, Q. Sphingolipid transport, rafts and translocators. J. Biol. Chem., 2002, 277, 25855-8
236. Micheau, O.; Tschopp, J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell, 2003, 114, 181-90.
237. So, T.; Lee, S.W.; Croft, M. Tumor necrosis factor/tumor necrosis factor receptor family members that positively regulate immunity. Int. J. Hematol., 2006, 83, 1-11.
238. Segui, B.; Cuvillier, O.; Adam-Klages, S.; Garcia, V.; Malagarie-Cazenave, S.; Leveque, S.; Caspar-Bauguil, S.; Coudert, J.; Salvayre, R.; Kronke, M.; Levade, T. Involvement of FAN in TNF-induced apoptosis. J. Clin. Invest., 2001, 108, 143-51
239. Malagarie-Cazenave, S.; Segui, B.; Leveque, S.; Garcia, V.; Carpentier, S.; Altie, M.F.; Brouchet, A.; Gouaze, V.; Andrieu-Abadie, N.; Barreira, Y.; Benoist, H.; Levade, T. Role of FAN in tumor necrosis factor-alpha and lipopolysaccharide-induced interleukin-6 secretion and lethality in D-galactosamine-sensitized mice. J. Biol. Chem., 2004, 279, 18648-55.
240. Schwandner, R.; Wiegmann, K.; Bernardo, K.; Kreder, D.; Kronke, M. TNF receptor death domain-associated proteins TRADD and FADD signal activation of acid sphingomyelinase. J. Biol. Chem., 1998, 273, 5916-22.
241. Adam-Klages, S.; Schwandner, R.; Adam, D.; Kreder, D.; Bernardo, K.; Kronke, M. Distinct adapter proteins mediate acid versus neutral sphingomyelinase activation through the p55 receptor for tumor necrosis factor. J. Leukoc. Biol., 1998, 63, 678-82.
242. Siskind, L.J.; Kolesnick, R.N.; Colombini, M. Ceramide channels increase the permeability of the mitochondrial outer membrane to small proteins. J. Biol. Chem., 2002, 277, 26796-803.
243. Siskind, L.J.; Kolesnick, R.N.; Colombini, M. Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrations. Mitochondrion, 2006, 6, 118-25
244. Garcia-Ruiz, C.; Colell, A.; Mari, M.; Morales, A.; Calvo, M.; Enrich, C.; Fernandez-Checa, J.C. Defective TNF-alpha-mediated hepatocellular apoptosis and liver damage in acidic sphingomyelinase knockout mice. J. Clin. Invest., 2003, 111, 197-208.
245. Osawa, Y.; Uchinami, H.; Bielawski, J.; Schwabe, R.F.; Hannun, Y.A.; Brenner, D.A. Roles for C16-ceramide and sphingosine 1-phosphate in regulating hepatocyte apoptosis in response to tumor necrosis factor-alpha. J. Biol. Chem., 2005, 280, 27879-87
246. Mari, M.; Colell, A.; Morales, A.; Paneda, C.; Varela-Nieto, I.; Garcia-Ruiz, C.; Fernandez-Checa, J.C. Acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor-induced lethal hepatitis. J. Clin. Invest., 2004, 113, 895-904.
247. Kolesnick, R.N.; Paley, A.E. 1,2-Diacylglycerols and phorbol esters stimulate phosphatidylcholine metabolism in GH3 pituitary cells. Evidence for separate mechanisms of action. J. Biol. Chem., 1987, 262, 9204-10.