Ceramide Synthases: Roles in Cell Physiology and Signaling

  • Johnny Stiban
  • Rotem Tidhar
  • Anthony H. Futerman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 688)


Ceramide synthases (CerS) are integral membrane proteins of the endoplasmic reticulum. Six mammalian CerS have been described, with each utilizing fatty acyl CoAs of relatively defined chain lengths for N-acylation of the sphingoid long chain base. In this chapter, we review the main functional features of the CerS proteins, discuss their fatty acid specificity, kinetics, tissue distribution and mode of inhibition, as well as possible posttranslational modifications. We then address the reason that mammals contain six distinct CerS, whereas most other enzymes in the sphingolipid biosynthetic pathway only occur in one or two isoforms. Finally, we discuss the putative roles of CerS and the ceramide derived from the CerS, in signaling pathways and in development of disease.


Acyl Chain Arsenic Trioxide Ceramide Synthesis CerS Activity Ulatory Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Hannun YA, Obeid LM, Wolff RA. The novel second messenger ceramide: identification, mechanism of action and cellular activity. Adv Lipid Res 1993; 25:43–64.PubMedGoogle Scholar
  2. 2.
    Hannun YA. Functions of ceramide in coordinating cellular responses to stress. Science 1996; 274:1855–1859.CrossRefPubMedGoogle Scholar
  3. 3.
    Futerman AH, Hannun YA. The complex life of simple sphingolipids. EMBO Rep 2004; 5:777–782.CrossRefPubMedGoogle Scholar
  4. 4.
    Futerman AH, Riezman H. The ins and outs of sphingolipid synthesis. Trends Cell Biol 2005; 15:312–318.CrossRefPubMedGoogle Scholar
  5. 5.
    Guillas I, Kirchman PA, Chuard R et al. C26-CoA-dependent ceramide synthesis of Saccharomyces cerevisiae is operated by Lag1p and Lac1p. Embo J 2001; 20:2655–2665.CrossRefPubMedGoogle Scholar
  6. 6.
    Schorling S, Vallee B, Barz WP et al. Lag1p and Lac1p are essential for the Acyl-CoA-dependent ceramide synthase reaction in Saccharomyces cerevisae. Mol Biol Cell 2001; 12:3417–3427.PubMedGoogle Scholar
  7. 7.
    Futerman AH, editor. Ceramide Signaling: Kluwer Academic/Plenum Publishers 2002.Google Scholar
  8. 8.
    Venkataraman K, Futerman A. Do longevity assurance genes containing Hox domains regulate cell development via ceramide synthesis? FEBS Lett 2002; 528:3–4.CrossRefPubMedGoogle Scholar
  9. 9.
    Winter E, Ponting CP. TRAM, LAG1 and CLN8: members of a novel family of lipid-sensing domains? Trends Biochem Sci 2002; 27:381–383.CrossRefPubMedGoogle Scholar
  10. 10.
    Pewzner-Jung Y, Ben-Dor S, Futerman AH. When do Lasses (longevity assurance genes) become CerS (ceramide synthases)?: Insights into the regulation of ceramide synthesis. J Biol Chem 2006; 281:25001–25005.CrossRefPubMedGoogle Scholar
  11. 11.
    Lahiri S, Futerman AH. LASS5 is a bona fide dihydroceramide synthase that selectively utilizes palmitoyl-CoA as acyl donor. J Biol Chem 2005; 280:33735–33738.CrossRefPubMedGoogle Scholar
  12. 12.
    Mizutani Y, Kihara A, Igarashi Y. Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem J 2005; 390:263–271.CrossRefPubMedGoogle Scholar
  13. 13.
    Mesika A, Ben-Dor S, Laviad EL et al. A new functional motif in Hox domain-containing ceramide synthases: identification of a novel region flanking the Hox and TLC domains essential for activity. J Biol Chem 2007; 282:27366–27373.CrossRefPubMedGoogle Scholar
  14. 14.
    Vallee B, Riezman H. Lip1p: a novel subunit of acyl-CoA ceramide synthase. Embo J 2005; 24:730–741.CrossRefPubMedGoogle Scholar
  15. 15.
    Schulz A, Mousallem T, Venkataramani M et al. The CLN9 protein, a regulator of dihydroceramide synthase. J Biol Chem 2006; 281:2784–2794.CrossRefPubMedGoogle Scholar
  16. 16.
    Venkataraman K, Riebeling C, Bodennec J et al. Upstream of growth and differentiation factor 1 (uog1), a mammalian homolog of the yeast longevity assurance gene 1 (LAG1), regulates N-stearoyl-sphinganine (C18-(dihydro)ceramide) synthesis in a fumonisin B1-independent manner in mammalian cells. J Biol Chem 2002; 277:35642–35649.CrossRefPubMedGoogle Scholar
  17. 17.
    Riebeling C, Allegood JC, Wang E et al. Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors. J Biol Chem 2003; 278:43452–43459.CrossRefPubMedGoogle Scholar
  18. 18.
    Mizutani Y, Kihara A, Igarashi Y. LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro)ceramide synthase with relatively broad substrate specificity. Biochem J 2006; 398:531–538.CrossRefPubMedGoogle Scholar
  19. 19.
    Laviad EL, Albee L, Pankova-Kholmyansky I et al. Characterization of ceramide synthase 2: tissue distribution, substrate specificity and inhibition by sphingosine 1-phosphate. J Biol Chem 2008; 283:5677–5684.CrossRefPubMedGoogle Scholar
  20. 20.
    Mizutani Y, Kihara A, Chiba H et al. 2-Hydroxy-ceramide synthesis by ceramide synthase family: enzymatic basis for the preference of FA chain length. J Lipid Res 2008; 49:2356–2364.CrossRefPubMedGoogle Scholar
  21. 21.
    Lahiri S, Lee H, Mesicek J et al. Kinetic characterization of mammalian ceramide synthases: determination of K(m) values towards sphinganine. FEBS Lett 2007; 581:5289–5294.CrossRefPubMedGoogle Scholar
  22. 22.
    Wang E, Merrill AH. Ceramide Synthase. Methods Enzymol 1999; 311:15–21.CrossRefGoogle Scholar
  23. 23.
    Xu Z, Zhou J, McCoy DM et al. LASS5 is the predominant ceramide synthase isoform involved in de novo sphingolipid synthesis in lung epithelia. J Lipid Res 2005; 46:1229–1238.CrossRefPubMedGoogle Scholar
  24. 24.
    Mandon EC, Ehses I, Rother J et al. Subcellular localization and membrane topology of serine palmitoyltransferase, 3-dehydrosphinganine reductase and sphinganine N-acyltransferase in mouse liver. J Biol Chem 1992; 267:11144–11148.PubMedGoogle Scholar
  25. 25.
    Hirschberg K, Rodger J, Futerman AH. The long-chain sphingoid base of sphingolipids is acylated at the cytosolic surface of the endoplasmic reticulum in rat liver. Biochem J 1993; 290:751–757.PubMedGoogle Scholar
  26. 26.
    Bionda C, Portoukalian J, Schmitt D et al. Subcellular compartmentalization of ceramide metabolism: MAM (mitochondria-associated membrane) and/or mitochondria? Biochem J 2004; 382:527–533.CrossRefPubMedGoogle Scholar
  27. 27.
    Yu J, Novgorodov SA, Chudakova D et al. JNK3 signaling pathway activates ceramide synthase leading to mitochondrial dysfunction. J Biol Chem 2007; 282:25940–25949.CrossRefPubMedGoogle Scholar
  28. 28.
    Wang E, Norred WP, Bacon CW et al. Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme. J Biol Chem 1991; 266:14486–14490.PubMedGoogle Scholar
  29. 29.
    Merrill AH Jr, van Echten G, Wang E et al. Fumonisin B1 inhibits sphingosine (sphinganine) N-acyltransferase and de novo sphingolipid biosynthesis in cultured neurons in situ. J Biol Chem 1993; 268:27299–27306.PubMedGoogle Scholar
  30. 30.
    Yoo HS, Norred WP, Wang E et al. Fumonisin inhibition of de novo sphingolipid biosynthesis and cytotoxicity are correlated in LLC-PK1 cells. Toxicol Appl Pharmacol 1992; 114:9–15.CrossRefPubMedGoogle Scholar
  31. 31.
    Wu WI, McDonough VM, Nickels JT et al. Regulation of lipid biosynthesis in Saccharomyces cerevisiae by fumonisin B1. J Biol Chem 1995; 270:13171–13178.CrossRefPubMedGoogle Scholar
  32. 32.
    Harel R, Futerman AH. Inhibition of sphingolipid synthesis affects axonal outgrowth in cultured hippocampal neurons. J Biol Chem 1993; 268:14476–14481.PubMedGoogle Scholar
  33. 33.
    Schwarz A, Futerman AH. Inhibition of sphingolipid synthesis, but not degradation, alters the rate of dendrite growth in cultured hippocampal neurons. Brain Res Dev Brain Res 1998; 108:125–130.CrossRefPubMedGoogle Scholar
  34. 34.
    Mandala SM, Thornton RA, Frommer BR et al. The discovery of australifungin, a novel inhibitor of sphinganine N-acyltransferase from Sporormiella australis. Producing organism, fermentation, isolation and biological activity. J Antibiot (Tokyo) 1995; 48:349–356.Google Scholar
  35. 35.
    Kobayashi SD, Nagiec MM. Ceramide/long-chain base phosphate rheostat in Saccharomyces cerevisiae: regulation of ceramide synthesis by Elo3p and Cka2p. Eukaryot Cell 2003; 2:284–294.CrossRefPubMedGoogle Scholar
  36. 36.
    Lahiri S, Park H, Laviad EL et al. Ceramide synthesis is modulated by the sphingosine analog FTY720 via a mixture of uncompetitive and non-competitive inhibition in an acyl CoA chain length-dependent manner. J Biol Chem 2009; 284:16090–16098.CrossRefPubMedGoogle Scholar
  37. 37.
    Bose R, Verheij M, Haimovitz-Friedman A et al. Ceramide synthase mediates daunorubicin-induced apoptosis: an alternative mechanism for generating death signals. Cell 1995; 82:405–414.CrossRefPubMedGoogle Scholar
  38. 38.
    Yano M, Kishida E, Muneyuki Y et al. Quantitative analysis of ceramide molecular species by high performance liquid chromatography. J Lipid Res 1998; 39:2091–2098.PubMedGoogle Scholar
  39. 39.
    Becker KP, Kitatani K, Idkowiak-Baldys J et al. Selective inhibition of juxtanuclear translocation of protein kinase C betaII by a negative feedback mechanism involving ceramide formed from the salvage pathway. J Biol Chem 2005; 280:2606–2612.CrossRefPubMedGoogle Scholar
  40. 40.
    Kitatani K, Idkowiak-Baldys J, Bielawski J et al. Protein kinase C-induced activation of a ceramide/protein phosphatase 1 pathway leading to dephosphorylation of p38 MAPK. J Biol Chem 2006; 281:36793–36802.CrossRefPubMedGoogle Scholar
  41. 41.
    Aronova S, Wedaman K, Aronov PA et al. Regulation of ceramide biosynthesis by TOR complex 2. Cell Metab 2008; 7:148–158.CrossRefPubMedGoogle Scholar
  42. 42.
    Mulet JM, Martin DE, Loewith R et al. Mutual antagonism of target of rapamycin and calcineurin signaling. J Biol Chem 2006; 281:33000–33007.CrossRefPubMedGoogle Scholar
  43. 43.
    Tabuchi M, Audhya A, Parsons AB et al. The phosphatidylinositol 4,5-biphosphate and TORC2 binding proteins Slm1 and Slm2 function in sphingolipid regulation. Mol Cell Biol 2006; 26:5861–5875.CrossRefPubMedGoogle Scholar
  44. 44.
    Wang YL, Wang Y, Tong L et al. Overexpression of calcineurin B subunit (CnB) enhances the oncogenic potential of HEK293 cells. Cancer Sci 2008; 99:1100–1108.CrossRefPubMedGoogle Scholar
  45. 45.
    Villen J, Beausoleil SA, Gerber SA et al. Large-scale phosphorylation analysis of mouse liver. Proc Natl Acad Sci USA 2007; 104:1488–1493.CrossRefPubMedGoogle Scholar
  46. 46.
    Min J, Mesika A, Sivaguru M et al. (Dihydro)ceramide synthase 1 regulated sensitivity to cisplatin is associated with the activation of p38 mitogen-activated protein kinase and is abrogated by sphingosine kinase 1. Mol Cancer Res 2007; 5:801–812.CrossRefPubMedGoogle Scholar
  47. 47.
    Sridevi P, Alexander H, Laviad EL et al. Ceramide synthase 1 is regulated by proteasomal mediated turnover. Biochim Biophys Acta 2009; 1793:1218–1227.PubMedGoogle Scholar
  48. 48.
    Kageyama-Yahara N, Riezman H. Transmembrane topology of ceramide synthase in yeast. Biochem J 2006; 398:585–593.CrossRefPubMedGoogle Scholar
  49. 49.
    Rost B. PHD: predicting one-dimensional protein structure by profile-based neural networks. Methods Enzymol 1996; 266:525–539.CrossRefPubMedGoogle Scholar
  50. 50.
    Sot J, Aranda FJ, Collado MI et al. Different effects of long-and short-chain ceramides on the gel-fluid and lamellar-hexagonal transitions of phospholipids: a calorimetric, NMR and x-ray diffraction study. Biophys J 2005; 88:3368–3380.CrossRefPubMedGoogle Scholar
  51. 51.
    Pinto SN, Silva LC, de Almeida RF et al. Membrane domain formation, interdigitation and morphological alterations induced by the very long chain asymmetric C24:1 ceramide. Biophys J 2008; 95:2867–2879.CrossRefPubMedGoogle Scholar
  52. 52.
    Kroesen BJ, Jacobs S, Pettus BJ et al. BcR-induced apoptosis involves differential regulation of C16 and C24-ceramide formation and sphingolipid-dependent activation of the proteasome. J Biol Chem 2003; 278:14723–14731.CrossRefPubMedGoogle Scholar
  53. 53.
    Koybasi S, Senkal CE, Sundararaj K et al. Defects in cell growth regulation by C18:0-ceramide and longevity assurance gene 1 in human head and neck squamous cell carcinomas. J Biol Chem 2004; 279:44311–44319.CrossRefPubMedGoogle Scholar
  54. 54.
    Senkal CE, Ponnusamy S, Rossi MJ et al. Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas. Mol Cancer Ther 2007; 6:712–722.CrossRefPubMedGoogle Scholar
  55. 55.
    Karahatay S, Thomas K, Koybasi S et al. Clinical relevance of ceramide metabolism in the pathogenesis of human head and neck squamous cell carcinoma (HNSCC): attenuation of C(18)-ceramide in HNSCC tumors correlates with lymphovascular invasion and nodal metastasis. Cancer Lett 2007; 256:101–111.CrossRefPubMedGoogle Scholar
  56. 56.
    Baran Y, Salas A, Senkal CE et al. Alterations of ceramide/sphingosine 1-phosphate rheostat involved in the regulation of resistance to imatinib-induced apoptosis in K562 human chronic myeloid leukemia cells. J Biol Chem 2007; 282:10922–10934.CrossRefPubMedGoogle Scholar
  57. 57.
    Becker I, Wang-Eckhardt L, Yaghootfam A et al. Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2. Histochem Cell Biol 2008; 129:233–241.CrossRefPubMedGoogle Scholar
  58. 58.
    Coderch L, Lopez O, de la Maza A et al. Ceramides and skin function. Am J Clin Dermatol 2003; 4:107–129.CrossRefPubMedGoogle Scholar
  59. 59.
    Rabionet M, van der Spoel AC, Chuang CC et al. Male germ cells require polyenoic sphingolipids with complex glycosylation for completion of meiosis: a link to ceramide synthase-3. J Biol Chem 2008; 283:13357–13369.CrossRefPubMedGoogle Scholar
  60. 60.
    Pettus BJ, Baes M, Busman M et al. Mass spectrometric analysis of ceramide perturbations in brain and fibroblasts of mice and human patients with peroxisomal disorders. Rapid Commun Mass Spectrom 2004; 18:1569–1574.CrossRefPubMedGoogle Scholar
  61. 61.
    Eto M, Bennouna J, Hunter OC et al. C16 ceramide accumulates following androgen ablation in LNCaP prostate cancer cells. Prostate 2003; 57:66–79.CrossRefPubMedGoogle Scholar
  62. 62.
    Osawa Y, Uchinami H, Bielawski J et al. Roles for C16-ceramide and sphingosine 1-phosphate in regulating hepatocyte apoptosis in response to tumor necrosis factor-alpha. J Biol Chem 2005; 280:27879–27887.CrossRefPubMedGoogle Scholar
  63. 63.
    Kolaczkowski M, Kolaczkowska A, Gaigg B et al. Differential regulation of ceramide synthase components LAC1 and LAG1 in Saccharomyces cerevisiae. Eukaryot Cell 2004; 3:880–892.CrossRefPubMedGoogle Scholar
  64. 64.
    Dickson RC. Thematic review series: sphingolipids. New insights into sphingolipid metabolism and function in budding yeast. J Lipid Res 2008; 49:909–921.CrossRefPubMedGoogle Scholar
  65. 65.
    Bartke N, Hannun YA. Bioactive sphingolipids: metabolism and function. J Lipid Res 2008.Google Scholar
  66. 66.
    Reynolds CP, Maurer BJ, Kolesnick RN. Ceramide synthesis and metabolism as a target for cancer therapy. Cancer Lett 2004; 206:169–180.CrossRefPubMedGoogle Scholar
  67. 67.
    Dbaibo GS, Kfoury Y, Darwiche N et al. Arsenic trioxide induces accumulation of cytotoxic levels of ceramide in acute promyelocytic leukemia and adult T-cell leukemia/lymphoma cells through de novo ceramide synthesis and inhibition of glucosylceramide synthase activity. Haematologica 2007; 92:753–762.CrossRefPubMedGoogle Scholar
  68. 68.
    Jin J, Hou Q, Mullen TD et al. Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced Bax redistribution to mitochondria in NT-2 cells. J Biol Chem 2008; 283:26509–26517.CrossRefPubMedGoogle Scholar
  69. 69.
    Panjarian S, Kozhaya L, Arayssi S et al. De novo N-palmitoylsphingosine synthesis is the major biochemical mechanism of ceramide accumulation following p53 up-regulation. Prostaglandins Other Lipid Mediat 2008; 86:41–48.CrossRefPubMedGoogle Scholar
  70. 70.
    Pandey S, Murphy RF, Agrawal DK. Recent advances in the immunobiology of ceramide. Exp Mol Pathol 2007; 82:298–309.CrossRefPubMedGoogle Scholar
  71. 71.
    Lahiri S, Futerman AH. The metabolism and function of sphingolipids and glycosphingolipids. Cell Mol Life Sci 2007; 64:2270–2284.CrossRefPubMedGoogle Scholar
  72. 72.
    Summers SA. Ceramides in insulin resistance and lipotoxicity. Prog Lipid Res 2006; 45:42–72.CrossRefPubMedGoogle Scholar
  73. 73.
    Ito Y, Sato S, Ohashi T et al. Reduction of airway anion secretion via CFTR in sphingomyelin pathway. Biochem Biophys Res Commun 2004; 324:901–908.CrossRefPubMedGoogle Scholar
  74. 74.
    Vilela RM, Lands LC, Meehan B et al. Inhibition of IL-8 release from CFTR-deficient lung epithelial cells following pretreatment with fenretinide. Int Immunopharmacol 2006; 6:1651–1664.CrossRefPubMedGoogle Scholar
  75. 75.
    Petrache I, Natarajan V, Zhen L et al. Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice. Nat Med 2005; 11:491–498.CrossRefPubMedGoogle Scholar
  76. 76.
    Petrache I, Natarajan V, Zhen L et al. Ceramide causes pulmonary cell apoptosis and emphysema: a role for sphingolipid homeostasis in the maintenance of alveolar cells. Proc Am Thorac Soc 2006; 3:510.CrossRefPubMedGoogle Scholar
  77. 77.
    Morales A, Lee H, Goni FM et al. Sphingolipids and cell death. Apoptosis 2007; 12:923–939.CrossRefPubMedGoogle Scholar
  78. 78.
    Llacuna L, Mari M, Garcia-Ruiz C et al. Critical role of acidic sphingomyelinase in murine hepatic ischemia-reperfusion injury. Hepatology 2006; 44:561–572.CrossRefPubMedGoogle Scholar
  79. 79.
    Mari M, Caballero F, Colell A et al. Mitochondrial free cholesterol loading sensitizes to TNF-and Fas-mediated steatohepatitis. Cell Metab 2006; 4:185–198.CrossRefPubMedGoogle Scholar
  80. 80.
    Lang PA, Schenck M, Nicolay JP et al. Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide. Nat Med 2007; 13:164–170.CrossRefPubMedGoogle Scholar
  81. 81.
    Cutler RG, Kelly J, Storie K et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer’s disease. Proc Natl Acad Sci USA 2004; 101:2070–2075.CrossRefPubMedGoogle Scholar
  82. 82.
    Wang G, Silva J, Dasgupta S et al. Long-chain ceramide is elevated in presenilin 1 (PS1M146V) mouse brain and induces apoptosis in PS1 astrocytes. Glia 2008; 56:449–456.CrossRefPubMedGoogle Scholar
  83. 83.
    Schwarz A, Futerman AH. Distinct roles for ceramide and glucosylceramide at different stages of neuronal growth. J Neurosci 1997; 17:2929–2938.PubMedGoogle Scholar
  84. 84.
    Lee JT, Xu J, Lee JM et al. Amyloid-beta peptide induces oligodendrocyte death by activating the neutral sphingomyelinase-ceramide pathway. J Cell Biol 2004; 164:123–131.CrossRefPubMedGoogle Scholar
  85. 85.
    Jana A, Pahan K. Fibrillar amyloid-beta peptides kill human primary neurons via NADPH oxidase-mediated activation of neutral sphingomyelinase. Implications for Alzheimer’s disease. J Biol Chem 2004; 279:51451–51459.CrossRefPubMedGoogle Scholar
  86. 86.
    Yu ZF, Nikolova-Karakashian M, Zhou D et al. Pivotal role for acidic sphingomyelinase in cerebral ischemia-induced ceramide and cytokine production and neuronal apoptosis. J Mol Neurosci 2000; 15:85–97.CrossRefPubMedGoogle Scholar
  87. 87.
    Uchida Y, Nardo AD, Collins V et al. De novo ceramide synthesis participates in the ultraviolet B irradiation-induced apoptosis in undifferentiated cultured human keratinocytes. J Invest Dermatol 2003; 120:662–669.CrossRefPubMedGoogle Scholar
  88. 88.
    Jenkins GM, Richards A, Wahl T et al. Involvement of yeast sphingolipids in the heat stress response of Saccharomyces cerevisiae. J Biol Chem 1997; 272:32566–32572.CrossRefPubMedGoogle Scholar
  89. 89.
    Wells GB, Dickson RC, Lester RL. Heat-induced elevation of ceramide in Saccharomyces cerevisiae via de novo synthesis. J Biol Chem 1998; 273:7235–7243.CrossRefPubMedGoogle Scholar
  90. 90.
    Jenkins GM, Cowart LA, Signorelli P et al. Acute activation of de novo sphingolipid biosynthesis upon heat shock causes an accumulation of ceramide and subsequent dephosphorylation of SR proteins. J Biol Chem 2002; 277:42572–42578.CrossRefPubMedGoogle Scholar
  91. 91.
    Perry DK, Carton J, Shah AK et al. Serine palmitoyltransferase regulates de novo ceramide generation during etoposide-induced apoptosis. J Biol Chem 2000; 275:9078–9084.CrossRefPubMedGoogle Scholar
  92. 92.
    Basnakian AG, Ueda N, Hong X et al. Ceramide synthase is essential for endonuclease-mediated death of renal tubular epithelial cells induced by hypoxia-reoxygenation. Am J Physiol Renal Physiol 2005; 288:F308–314.CrossRefPubMedGoogle Scholar
  93. 93.
    Cuzzocrea S, Di Paola R, Genovese T et al. Anti-inflammatory and anti-apoptotic effects of fumonisin B1, an inhibitor of ceramide synthase, in a rodent model of splanchnic ischemia and reperfusion injury. J Pharmacol Exp Ther 2008; 327:45–57.CrossRefPubMedGoogle Scholar
  94. 94.
    Meyer SG, de Groot H. Cycloserine and threo-dihydrosphingosine inhibit TNF-alpha-induced cytotoxicity: evidence for the importance of de novo ceramide synthesis in TNF-alpha signaling. Biochim Biophys Acta 2003; 1643:1–4.PubMedGoogle Scholar
  95. 95.
    Veluthakal R, Jangati GR, Kowluru A. IL-1beta-induced iNOS expression, NO release and loss in metabolic cell viability are resistant to inhibitors of ceramide synthase and sphingomyelinase in INS 832/13 cells. Jop 2006; 7:593–601.PubMedGoogle Scholar
  96. 96.
    Turnbull KJ, Brown BL, Dobson PR. Caspase-3-like activity is necessary but not sufficient for daunorubicin-induced apoptosis in Jurkat human lymphoblastic leukemia cells. Leukemia 1999; 13:1056–1061.CrossRefPubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  • Johnny Stiban
    • 1
  • Rotem Tidhar
    • 1
  • Anthony H. Futerman
    • 1
  1. 1.Department of Biological ChemistryWeizmann Institute of ScienceRehovotIsrael

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