The consequences of genetic and pharmacologic reduction in sphingolipid synthesis

Journal of Inherited Metabolic Disease

Volumn 38, Issue 1, 2015, Pages 77-84

  Schiffmann, Raphael ^a  

^a BAYLOR UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CERAMIDE; CERAMIDE GLUCOSYLTRANSFERASE; CERAMIDE SYNTHASE; FUMONISIN B1; SERINE PALMITOYLTRANSFERASE; SPHINGOLIPID; SPHINGOMYELIN; SPHINGOMYELIN SYNTHASE; THERMOZYMOCIDIN; UNCLASSIFIED DRUG; GLUCOSE; GLUCOSYLTRANSFERASE; URIDINE DIPHOSPHATE;

ARTICLE; ASTHMA; ATHEROSCLEROSIS; DIABETES MELLITUS; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME SPECIFICITY; ENZYME SYNTHESIS; GENETICS; KIDNEY POLYCYSTIC DISEASE; LYSOSOME STORAGE DISEASE; NONHUMAN; RISK FACTOR; SPHINGOLIPID METABOLISM; ANIMAL; BIOSYNTHESIS; CHEMISTRY; DISEASE MODEL; HUMAN; LIPID METABOLISM; LIPIDOSIS; LYSOSOME; METABOLISM; MOUSE;

ANIMALS; ASTHMA; ATHEROSCLEROSIS; DIABETES MELLITUS; DISEASE MODELS, ANIMAL; GLUCOSE; GLUCOSYLTRANSFERASES; HUMANS; LIPID METABOLISM; LYSOSOMES; MICE; POLYCYSTIC KIDNEY DISEASES; SERINE C-PALMITOYLTRANSFERASE; SPHINGOLIPIDOSES; SPHINGOLIPIDS; URIDINE DIPHOSPHATE;

EID: 84920067434     PISSN: 01418955     EISSN: 15732665     Source Type: Journal    
DOI: 10.1007/s10545-014-9758-8     Document Type: Article

References (90)

1. Abe A, Gregory S, Lee L et al (2000) Reduction of globotriaosylceramide in fabry disease mice by substrate deprivation. J Clin Invest 105(11):1563–1571
2. Aerts JM, Ottenhoff R, Powlson AS et al (2007) Pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivity. Diabetes 56(5):1341–1349
3. Andersson U, Smith D, Jeyakumar M et al (2004) Improved outcome of N-butyldeoxygalactonojirimycin-mediated substrate reduction therapy in a mouse model of Sandhoff disease. Neurobiol Dis 16(3):506–515
4. Arthur JR, Wilson MW, Larsen SD, Rockwell HE, Shayman JA, Seyfried TN (2013) Ethylenedioxy-PIP2 oxalate reduces ganglioside storage in juvenile sandhoff disease mice. Neurochem Res 38(4):866–875
5. Ashe KM, Bangari D, Li L et al (2011) Iminosugar-based inhibitors of glucosylceramide synthase increase brain glycosphingolipids and survival in a mouse model of sandhoff disease. PLoS One 6(6):e21758
6. Bietrix F, Lombardo E, van Roomen CP et al (2010) Inhibition of glycosphingolipid synthesis induces a profound reduction of plasma cholesterol and inhibits atherosclerosis development in APOE*3 Leiden and low-density lipoprotein receptor-/- mice. Arterioscler Thromb Vasc Biol 30(5):931–937
7. Boot RG, Verhoek M, Donker-Koopman W et al (2007) Identification of the non-lysosomal glucosylceramidase as beta-glucosidase 2. J Biol Chem 282(2):1305–1312
8. Boukhris A, Schule R, Loureiro JL et al (2013) Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. Am J Hum Genet 93(1):118–123
9. Bremer EG, Hakomori S, Bowen-Pope DF, Raines E, Ross R (1984) Ganglioside-mediated modulation of cell growth, growth factor binding, and receptor phosphorylation. J Biol Chem 259(11):6818–6825
10. Breslow DK, Weissman JS (2010) Membranes in balance: mechanisms of sphingolipid homeostasis. Mol Cell 40(2):267–279
11. Cabrera-Salazar MA, Deriso M, Bercury SD et al (2012) Systemic delivery of a glucosylceramide synthase inhibitor reduces CNS substrates and increases lifespan in a mouse model of type 2 Gaucher disease. PLoS One 7(8):e43310
12. Chatterjee S, Alsaeedi N (2012) Lactosylceramide synthase as a therapeutic target to mitigate multiple human diseases in animal models. Adv Exp Med Biol 749:153–169
13. Chatterjee S, Kolmakova A, Rajesh M (2008) Regulation of lactosylceramide synthase (glucosylceramide beta1– > 4 galactosyltransferase); implication as a drug target. Curr Drug Targets 9(4):272–281
14. Chatterjee S, Bedja D, Mishra S, et al (2014) Inhibition of glycosphingolipid synthesis ameliorates atherosclerosis and arterial stiffness in apo E-/- mice and rabbits fed a high fat and cholesterol diet. Circulation doi: 10.1161/CIRCULATIONAHA.113.007559.
15. Chun L, Junlin Z, Aimin W, Niansheng L, Benmei C, Minxiang L (2011) Inhibition of ceramide synthesis reverses endothelial dysfunction and atherosclerosis in streptozotocin-induced diabetic rats. Diabetes Res Clin Pract 93(1):77–85
16. Coetzee T, Fujita N, Dupree J et al (1996) Myelination in the absence of galactocerebroside and sulfatide: normal structure with abnormal function and regional instability. Cell 86(2):209–219
17. Cuzzocrea S, Di Paola R, Genovese T et al (2008) 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 327(1):45–57
18. Dawkins JL, Hulme DJ, Brahmbhatt SB, Auer-Grumbach M, Nicholson GA (2001) Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat Genet 27(3):309–312
19. Deshmukh GD, Radin NS, Gattone VH 2nd, Shayman JA (1994) Abnormalities of glycosphingolipid, sulfatide, and ceramide in the polycystic (cpk/cpk) mouse. J Lipid Res 35(9):1611–1618
20. Eichler FS, Hornemann T, McCampbell A et al (2009) Overexpression of the wild-type SPT1 subunit lowers desoxysphingolipid levels and rescues the phenotype of HSAN1. J Neurosci 29(46):14646–14651
21. Elstein D, Hollak C, Aerts JM et al (2004) Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type I Gaucher disease. J Inherit Metab Dis 27(6):757–766
22. Fan Y, Shi F, Liu J et al (2010) Selective reduction in the sphingomyelin content of atherogenic lipoproteins inhibits their retention in murine aortas and the subsequent development of atherosclerosis. Arterioscler Thromb Vasc Biol 30(11):2114–2120
23. Fragaki K, Ait-El-Mkadem S, Chaussenot A et al (2013) Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency. Eur J Hum Genet 21(5):528–534
24. Futerman AH, Hannun YA (2004) The complex life of simple sphingolipids. EMBO Rep 5(8):777–782
25. Gable K, Gupta SD, Han G, Niranjanakumari S, Harmon JM, Dunn TM (2010) A disease-causing mutation in the active site of serine palmitoyltransferase causes catalytic promiscuity. J Biol Chem 285(30):22846–22852
26. Garofalo K, Penno A, Schmidt BP et al (2011) Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. J Clin Invest 121(12):4735–4745
27. Glaros EN, Kim WS, Quinn CM, Jessup W, Rye KA, Garner B (2008) Myriocin slows the progression of established atherosclerotic lesions in apolipoprotein E gene knockout mice. J Lipid Res 49(2):324–331
28. Hailemariam TK, Huan C, Liu J et al (2008) Sphingomyelin synthase 2 deficiency attenuates NFkappaB activation. Arterioscler Thromb Vasc Biol 28(8):1519–1526
29. Hannun YA, Obeid LM (2008) Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 9(2):139–150
30. Hla T, Dannenberg AJ (2012) Sphingolipid signaling in metabolic disorders. Cell Metab 16(4):420–434
31. Hojjati MR, Li Z, Jiang XC (2005a) Serine palmitoyl-CoA transferase (SPT) deficiency and sphingolipid levels in mice. Biochim Biophys Acta 1737(1):44–51
32. Hojjati MR, Li Z, Zhou H et al (2005b) Effect of myriocin on plasma sphingolipid metabolism and atherosclerosis in apoE-deficient mice. J Biol Chem 280(11):10284–10289
33. Honke K, Hirahara Y, Dupree J et al (2002) Paranodal junction formation and spermatogenesis require sulfoglycolipids. Proc Natl Acad Sci U S A 99(7):4227–4232
34. Hornemann T, Richard S, Rutti MF, Wei Y, von Eckardstein A (2006) Cloning and initial characterization of a new subunit for mammalian serine-palmitoyltransferase. J Biol Chem 281(49):37275–37281
35. Inokuchi J, Mason I, Radin NS (1987) Antitumor activity via inhibition of glycosphingolipid biosynthesis. Cancer Lett 38(1–2):23–30
36. Inoue M, Fujii Y, Furukawa K et al (2002) Refractory skin injury in complex knock-out mice expressing only the GM3 ganglioside. J Biol Chem 277(33):29881–29888
37. Jennemann R, Sandhoff R, Wang S et al (2005) Cell-specific deletion of glucosylceramide synthase in brain leads to severe neural defects after birth. Proc Natl Acad Sci U S A 102(35):12459–12464
38. Jeyakumar M, Norflus F, Tifft CJ et al (2001) Enhanced survival in Sandhoff disease mice receiving a combination of substrate deprivation therapy and bone marrow transplantation. Blood 97(1):327–329
39. Karman J, Tedstone JL, Gumlaw NK et al (2010) Reducing glycosphingolipid biosynthesis in airway cells partially ameliorates disease manifestations in a mouse model of asthma. Int Immunol 22(7):593–603
40. Kumagai T, Sato T, Natsuka S et al (2010) Involvement of murine beta-1,4-galactosyltransferase V in lactosylceramide biosynthesis. Glycoconj J 27(7–9):685–695
41. Kurek K, Wiesiolek-Kurek P, Piotrowska DM, Lukaszuk B, Chabowski A, Zendzian-Piotrowska M (2014) Inhibition of ceramide de novo synthesis with myriocin affects lipid metabolism in the liver of rats with streptozotocin-induced type 1 diabetes. Biomed Res Int 2014:980815
42. Langeveld M, van den Berg SA, Bijl N et al (2012) Treatment of genetically obese mice with the iminosugar N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin reduces body weight by decreasing food intake and increasing fat oxidation. Metabolism 61(1):99–107
43. Lee SY, Kim JR, Hu Y et al (2012) Cardiomyocyte specific deficiency of serine palmitoyltransferase subunit 2 reduces ceramide but leads to cardiac dysfunction. J Biol Chem 287(22):18429–18439
44. Li Z, Park TS, Li Y et al (2009) Serine palmitoyltransferase (SPT) deficient mice absorb less cholesterol. Biochim Biophys Acta 1791(4):297–306
45. Li Z, Fan Y, Liu J et al (2012) Impact of sphingomyelin synthase 1 deficiency on sphingolipid metabolism and atherosclerosis in mice. Arterioscler Thromb Vasc Biol 32(7):1577–1584
46. Liu Y, Wada R, Kawai H et al (1999) A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder. J Clin Invest 103(4):497–505
47. Liu J, Huan C, Chakraborty M et al (2009a) Macrophage sphingomyelin synthase 2 deficiency decreases atherosclerosis in mice. Circ Res 105(3):295–303
48. Liu J, Zhang H, Li Z et al (2009b) Sphingomyelin synthase 2 is one of the determinants for plasma and liver sphingomyelin levels in mice. Arterioscler Thromb Vasc Biol 29(6):850–856
49. Lombardo E, van Roomen CP, van Puijvelde GH et al (2012) Correction of liver steatosis by a hydrophobic iminosugar modulating glycosphingolipids metabolism. PLoS One 7(10):e38520
50. Lukina E, Watman N, Arreguin EA et al (2010) A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood 116(6):893–899
51. Marshall J, Ashe KM, Bangari D et al (2010a) Substrate reduction augments the efficacy of enzyme therapy in a mouse model of Fabry disease. PLoS One 5(11):e15033
52. Marshall J, McEachern KA, Chuang WL et al (2010b) Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy. J Inherit Metab Dis 33(3):281–289
53. McDonald G, Deepak S, Miguel L et al (2014) Normalizing glycosphingolipids restores function in CD4+ T cells from lupus patients. J Clin Invest 124(2):712–724
54. Miyake Y, Kozutsumi Y, Nakamura S, Fujita T, Kawasaki T (1995) Serine palmitoyltransferase is the primary target of a sphingosine-like immunosuppressant, ISP-1/myriocin. Biochem Biophys Res Commun 211(2):396–403
55. Mullen TD, Hannun YA, Obeid LM (2012) Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem J 441(3):789–802
56. Natoli TA, Smith LA, Rogers KA et al (2010) Inhibition of glucosylceramide accumulation results in effective blockade of polycystic kidney disease in mouse models. Nat Med 16(7):788–792
57. Nietupski JB, Pacheco JJ, Chuang WL et al (2012) Iminosugar-based inhibitors of glucosylceramide synthase prolong survival but paradoxically increase brain glucosylceramide levels in Niemann-Pick C mice. Mol Genet Metab 105(4):621–628
58. Nishie T, Hikimochi Y, Zama K et al (2010) Beta4-galactosyltransferase-5 is a lactosylceramide synthase essential for mouse extra-embryonic development. Glycobiology 20(10):1311–1322
59. Ohmi Y, Tajima O, Ohkawa Y, Mori A, Sugiura Y, Furukawa K (2009) Gangliosides play pivotal roles in the regulation of complement systems and in the maintenance of integrity in nerve tissues. Proc Natl Acad Sci U S A 106(52):22405–22410
60. Ohta E, Ohira T, Matsue K et al (2009) Analysis of development of lesions in mice with serine palmitoyltransferase (SPT) deficiency -Sptlc2 conditional knockout mice. Exp Anim 58(5):515–524
61. Okada M, Itoh Mi M, Haraguchi M et al (2002) B-series ganglioside deficiency exhibits no definite changes in the neurogenesis and the sensitivity to fas-mediated apoptosis but impairs regeneration of the lesioned hypoglossal nerve. J Biol Chem 277(3):1633–1636
62. Okuda T, Tokuda N, Numata S et al (2006) Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins. J Biol Chem 281(15):10230–10235
63. Okuda T, Furukawa K, Nakayama K (2009) A novel, promoter-based, target-specific assay identifies 2-deoxy-D-glucose as an inhibitor of globotriaosylceramide biosynthesis. Febs J 276(18):5191–5202
64. Osuchowski MF, Johnson VJ, He Q, Sharma RP (2004) Myriocin, a serine palmitoyltransferase inhibitor, alters regional brain neurotransmitter levels without concurrent inhibition of the brain sphingolipid biosynthesis in mice. Toxicol Lett 147(1):87–94
65. Overkleeft HS, Renkema GH, Neele J et al (1998) Generation of specific deoxynojirimycin-type inhibitors of the non-lysosomal glucosylceramidase. J Biol Chem 273(41):26522–26527
66. Park TS, Panek RL, Mueller SB et al (2004) Inhibition of sphingomyelin synthesis reduces atherogenesis in apolipoprotein E-knockout mice. Circulation 110(22):3465–3471
67. Park TS, Panek RL, Rekhter MD et al (2006) Modulation of lipoprotein metabolism by inhibition of sphingomyelin synthesis in ApoE knockout mice. Atherosclerosis 189(2):264–272
68. Park TS, Rosebury W, Kindt EK, Kowala MC, Panek RL (2008) Serine palmitoyltransferase inhibitor myriocin induces the regression of atherosclerotic plaques in hyperlipidemic ApoE-deficient mice. Pharmacol Res 58(1):45–51
69. Park JW, Park WJ, Futerman AH (2014) Ceramide synthases as potential targets for therapeutic intervention in human diseases. Biochim Biophys Acta 1841(5):671–681
70. Peterschmitt MJ, Burke A, Blankstein L et al (2011) Safety, tolerability, and pharmacokinetics of eliglustat tartrate (Genz-112638) after single doses, multiple doses, and food in healthy volunteers. J Clin Pharmacol 51(5):695–705
71. Pontier SM, Schweisguth F (2012) Glycosphingolipids in signaling and development: from liposomes to model organisms. Dev Dyn 241(1):92–106
72. Russo SB, Tidhar R, Futerman AH, Cowart LA (2013) Myristate-derived d16:0 sphingolipids constitute a cardiac sphingolipid pool with distinct synthetic routes and functional properties. J Biol Chem 288(19):13397–13409
73. Saadat L, Dupree JL, Kilkus J et al (2010) Absence of oligodendroglial glucosylceramide synthesis does not result in CNS myelin abnormalities or alter the dysmyelinating phenotype of CGT-deficient mice. Glia 58(4):391–398
74. Schiffmann R (2009) Fabry disease. Pharmacol Ther 122(1):65–77
75. Shayman JA (2013) The design and clinical development of inhibitors of glycosphingolipid synthesis: will invention be the mother of necessity? Trans Am Clin Climatol Assoc 124:46–60
76. Sheikh KA, Sun J, Liu Y et al (1999) Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects. Proc Natl Acad Sci U S A 96(13):7532–7537
77. Simpson MA, Cross H, Proukakis C et al (2004) Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase. Nat Genet 36(11):1225–1229
78. Takamiya K, Yamamoto A, Furukawa K et al (1996) Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system. Proc Natl Acad Sci U S A 93(20):10662–10667
79. Ternes P, Brouwers JF, van den Dikkenberg J, Holthuis JC (2009) Sphingomyelin synthase SMS2 displays dual activity as ceramide phosphoethanolamine synthase. J Lipid Res 50(11):2270–2277
80. Togayachi A, Kozono Y, Ikehara Y et al (2010) Lack of lacto/neolacto-glycolipids enhances the formation of glycolipid-enriched microdomains, facilitating B cell activation. Proc Natl Acad Sci U S A 107(26):11900–11905
81. Vacaru AM, Tafesse FG, Ternes P et al (2009) Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER. J Cell Biol 185(6):1013–1027
82. Wennekes T, Meijer AJ, Groen AK et al (2010) Dual-action lipophilic iminosugar improves glycemic control in obese rodents by reduction of visceral glycosphingolipids and buffering of carbohydrate assimilation. J Med Chem 53(2):689–698
83. Worgall TS (2011) Sphingolipid synthetic pathways are major regulators of lipid homeostasis. Adv Exp Med Biol 721:139–148
84. Yamashita T, Wada R, Sasaki T et al (1999) A vital role for glycosphingolipid synthesis during development and differentiation. Proc Natl Acad Sci U S A 96(16):9142–9147
85. Yamashita T, Hashiramoto A, Haluzik M et al (2003) Enhanced insulin sensitivity in mice lacking ganglioside GM3. Proc Natl Acad Sci U S A 100(6):3445–3449
86. Yamashita T, Allende ML, Kalkofen DN, Werth N, Sandhoff K, Proia RL (2005a) Conditional LoxP-flanked glucosylceramide synthase allele controlling glycosphingolipid synthesis. Genesis 43(4):175–180
87. Yamashita T, Wu YP, Sandhoff R et al (2005b) Interruption of ganglioside synthesis produces central nervous system degeneration and altered axon-glial interactions. Proc Natl Acad Sci U S A 102(8):2725–2730
88. Yoshikawa M, Go S, Takasaki K et al (2009) Mice lacking ganglioside GM3 synthase exhibit complete hearing loss due to selective degeneration of the organ of Corti. Proc Natl Acad Sci U S A 106(23):9483–9488
89. Zhao H, Przybylska M, Wu IH et al (2007) Inhibiting glycosphingolipid synthesis improves glycemic control and insulin sensitivity in animal models of type 2 diabetes. Diabetes 56(5):1210–1218
90. Zimran A, Elstein D (2003) Gaucher disease and the clinical experience with substrate reduction therapy. Philos Trans R Soc Lond B Biol Sci 358(1433):961–966