Roles and regulation of neutral sphingomyelinase-2 in cellular and pathological processes

Advances in Biological Regulation

Volumn 57, Issue , 2015, Pages 24-41

  Shamseddine, Achraf A ^a,b   Airola, Michael V ^a,b   Hannun, Yusuf A ^a,b  

^a STONY BROOK UNIVERSITY   (United States)

^b Stony Brook Medicine   (United States)

Author keywords

Apoptosis; Ceramide; Exosomes; Inflammation; Sphingomyelinase

Indexed keywords

CERAMIDE; SMPD3 PROTEIN, HUMAN; SPHINGOMYELIN; SPHINGOMYELIN PHOSPHODIESTERASE; TUMOR PROTEIN;

ALZHEIMER DISEASE; ANIMAL; APOPTOSIS; EXOSOME; GENETIC TRANSCRIPTION; GENETICS; HUMAN; METABOLISM; METASTASIS; NEOPLASM; PATHOLOGY; PROTEIN PROCESSING; SIGNAL TRANSDUCTION;

ALZHEIMER DISEASE; ANIMALS; APOPTOSIS; CERAMIDES; EXOSOMES; HUMANS; NEOPLASM METASTASIS; NEOPLASM PROTEINS; NEOPLASMS; PROTEIN PROCESSING, POST-TRANSLATIONAL; SIGNAL TRANSDUCTION; SPHINGOMYELIN PHOSPHODIESTERASE; SPHINGOMYELINS; TRANSCRIPTION, GENETIC;

EID: 84920856216     PISSN: 22124926     EISSN: None     Source Type: Book Series    
DOI: 10.1016/j.jbior.2014.10.002     Document Type: Review

References (155)

1. Adam D., Wiegmann K., Adam-Klages S., Ruff A., Kronke M. Anovel cytoplasmic domain of the p55 tumor necrosis factor receptor initiates the neutral sphingomyelinase pathway. JBiol Chem 1996, 271:14617-14622.
2. Adam-Klages S., Adam D., Wiegmann K., Struve S., Kolanus W., Schneider-Mergener J., et al. FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingomyelinase. Cell 1996, 86:937-947.
3. 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. JLeukoc Biol 1998, 63:678-682.
4. Adamy C., Mulder P., Khouzami L., Andrieu-abadie N., Defer N., Candiani G., et al. Neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats. JMol Cell Cardiol 2007, 43:344-353.
5. Ago H., Oda M., Takahashi M., Tsuge H., Ochi S., Katunuma N., et al. Structural basis of the sphingomyelin phosphodiesterase activity in neutral sphingomyelinase from Bacillus cereus. JBiol Chem 2006, 281:16157-16167.
6. Ahn K.H., Kim S.K., Choi J.M., Jung S.Y., Won J.H., Back M.J., et al. Identification of heat shock protein 60 as a regulator of neutral sphingomyelinase 2 and its role in dopamine uptake. PLoS One 2013, 8:e67216.
7. Airola M.V., Hannun Y.A. Sphingolipid metabolism and neutral sphingomyelinases. Handbook of experimental pharmacology 2013, 57-76.
8. Altura B.M., Shah N.C., Shah G.J., Li W., Zhang A., Zheng T., et al. Magnesium deficiency upregulates sphingomyelinases in cardiovascular tissues and cells: cross-talk among proto-oncogenes, Mg(2+), NF-kappaB and ceramide and their potential relationships to resistant hypertension, atherogenesis and cardiac failure. Int J Clin Exp Med 2013, 6:861-879.
9. 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 Eur J Chem Biol 2001, 2:141-143.
10. Aubin I., Adams C.P., Opsahl S., Septier D., Bishop C.E., Auge N., et al. Adeletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse. Nat Genet 2005, 37:803-805.
11. Ayasolla K., Khan M., Singh A.K., Singh I. Inflammatory mediator and beta-amyloid (25-35)-induced ceramide generation and iNOS expression are inhibited by vitamin E. Free Radic Biol Med 2004, 37:325-338.
12. Baranowski M., Blachnio-Zabielska A., Hirnle T., Harasiuk D., Matlak K., Knapp M., et al. Myocardium of type 2 diabetic and obese patients is characterized by alterations in sphingolipid metabolic enzymes but not by accumulation of ceramide. JLipid Res 2010, 51:74-80.
13. Barsacchi R., Perrotta C., Bulotta S., Moncada S., Borgese N., Clementi E. Activation of endothelial nitric-oxide synthase by tumor necrosis factor-alpha: a novel pathway involving sequential activation of neutral sphingomyelinase, phosphatidylinositol-3' kinase, and Akt. Mol Pharmacol 2003, 63:886-895.
14. Barth B.M., Gustafson S.J., Kuhn T.B. Neutral sphingomyelinase activation precedes NADPH oxidase-dependent damage in neurons exposed to the proinflammatory cytokine tumor necrosis factor-alpha. JNeurosci Res 2012, 90:229-242.
15. Belka C., Wiegmann K., Adam D., Holland R., Neuloh M., Herrmann F., et al. Tumor necrosis factor (TNF)-alpha activates c-raf-1 kinase via the p55 TNF receptor engaging neutral sphingomyelinase. EMBO J 1995, 14:1156-1165.
16. Bhati R., Patterson C., Livasy C.A., Fan C., Ketelsen D., Hu Z., et al. Molecular characterization of human breast tumor vascular cells. Am J Pathol 2008, 172:1381-1390.
17. Brann A.B., Tcherpakov M., Williams I.M., Futerman A.H., Fainzilber M. Nerve growth factor-induced p75-mediated death of cultured hippocampal neurons is age-dependent and transduced through ceramide generated by neutral sphingomyelinase. JBiol Chem 2002, 277:9812-9818.
18. Bruno A.P., Laurent G., Averbeck D., Demur C., Bonnet J., Bettaieb A., et al. Lack of ceramide generation in TF-1 human myeloid leukemic cells resistant to ionizing radiation. Cell Death Differ 1998, 5:172-182.
19. Canals D., Perry D.M., Jenkins R.W., Hannun Y.A. Drug targeting of sphingolipid metabolism: sphingomyelinases and ceramidases. Br J Pharmacol 2011, 163:694-712.
20. Candalija A., Cubi R., Ortega A., Aguilera J., Gil C. Trk receptors need neutral sphingomyelinase activity to promote cell viability. FEBS Lett 2014, 588:167-174.
21. Castillo S.S., Levy M., Thaikoottathil J.V., Goldkorn T. Reactive nitrogen and oxygen species activate different sphingomyelinases to induce apoptosis in airway epithelial cells. Exp Cell Res 2007, 313:2680-2686.
22. Chaube R., Kallakunta V.M., Espey M.G., McLarty R., Faccenda A., Ananvoranich S., et al. Endoplasmic reticulum stress-mediated inhibition of NSMase2 elevates plasma membrane cholesterol and attenuates NO production in endothelial cells. Biochim Biophys Acta 2012, 1821:313-323.
23. Chen B.C., Chang H.M., Hsu M.J., Shih C.M., Chiu Y.H., Chiu W.T., et al. Peptidoglycan induces cyclooxygenase-2 expression in macrophages by activating the neutral sphingomyelinase-ceramide pathway. JBiol Chem 2009, 284:20562-20573.
24. Chi L.N., Tabuchi K., Nakamagoe M., Nakayama M., Nishimura B., Hara A. Ceramide/sphingomyelin cycle involvement in gentamicin-induced cochlear hair cell death. Arch Toxicol 2014, [Epub ahead of print].
25. Chipuk J.E., McStay G.P., Bharti A., Kuwana T., Clarke C.J., Siskind L.J., et al. Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial pathway of apoptosis. Cell 2012, 148:988-1000.
26. Clarke C.J., Guthrie J.M., Hannun Y.A. Regulation of neutral sphingomyelinase-2 (nSMase2) by tumor necrosis factor-alpha involves protein kinase C-delta in lung epithelial cells. Mol Pharmacol 2008, 74:1022-1032.
27. Clarke C.J., Mediwala K., Jenkins R.W., Sutton C.A., Tholanikunnel B.G., Hannun Y.A. Neutral sphingomyelinase-2 mediates growth arrest by retinoic acid through modulation of ribosomal S6 kinase. JBiol Chem 2011, 286:21565-21576.
28. Clarke C.J., Truong T.G., Hannun Y.A. Role for neutral sphingomyelinase-2 in tumor necrosis factor alpha-stimulated expression of vascular cell adhesion molecule-1 (VCAM) and intercellular adhesion molecule-1 (ICAM) in lung epithelial cells: p38 MAPK is an upstream regulator of nSMase2. JBiol Chem 2007, 282:1384-1396.
29. Clarke C.J., Wu B.X., Hannun Y.A. The neutral sphingomyelinase family: identifying biochemical connections. Adv Enzyme Regul 2011, 51:51-58.
30. Cogolludo A., Moreno L., Frazziano G., Moral-Sanz J., Menendez C., Castaneda J., et al. Activation of neutral sphingomyelinase is involved in acute hypoxic pulmonary vasoconstriction. Cardiovasc Res 2009, 82:296-302.
31. Czarny M., Liu J., Oh P., Schnitzer J.E. Transient mechanoactivation of neutral sphingomyelinase in caveolae to generate ceramide. JBiol Chem 2003, 278:4424-4430.
32. Czarny M., Schnitzer J.E. Neutral sphingomyelinase inhibitor scyphostatin prevents and ceramide mimics mechanotransduction in vascular endothelium. Am J Physiol Heart Circ Physiol 2004, 287:H1344-H1352.
33. De Palma C., Meacci E., Perrotta C., Bruni P., Clementi E. Endothelial nitric oxide synthase activation by tumor necrosis factor alpha through neutral sphingomyelinase 2, sphingosine kinase 1, and sphingosine 1 phosphate receptors: a novel pathway relevant to the pathophysiology of endothelium. Arterioscler Thromb Vasc Biol 2006, 26:99-105.
34. Dinkins M.B., Dasgupta S., Wang G., Zhu G., Bieberich E. Exosome reduction invivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer's disease. Neurobiol Aging 2014, 35:1792-1800.
35. Dobierzewska A., Giltiay N.V., Sabapathi S., Karakashian A.A., Nikolova-Karakashian M.N. Protein phosphatase 2A and neutral sphingomyelinase 2 regulate IRAK-1 protein ubiquitination and degradation in response to interleukin-1beta. JBiol Chem 2011, 286:32064-32073.
36. Dobierzewska A., Shi L., Karakashian A.A., Nikolova-Karakashian M.N. Interleukin 1beta regulation of FoxO1 protein content and localization: evidence for a novel ceramide-dependent mechanism. JBiol Chem 2012, 287:44749-44760.
37. Dobrowsky R.T., Jenkins G.M., Hannun Y.A. Neurotrophins induce sphingomyelin hydrolysis. Modulation by co-expression of p75NTR with Trk receptors. JBiol Chem 1995, 270:22135-22142.
38. Dobrowsky R.T., Werner M.H., Castellino A.M., Chao M.V., Hannun Y.A. Activation of the sphingomyelin cycle through the low-affinity neurotrophin receptor. Science 1994, 265:1596-1599.
39. Dressler K.A., Mathias S., Kolesnick R.N. Tumor necrosis factor-alpha activates the sphingomyelin signal transduction pathway in a cell-free system. Science 1992, 255:1715-1718.
40. Ferrer P., Asensi M., Priego S., Benlloch M., Mena S., Ortega A., et al. Nitric oxide mediates natural polyphenol-induced Bcl-2 down-regulation and activation of cell death in metastatic B16 melanoma. JBiol Chem 2007, 282:2880-2890.
41. Filosto S., Ashfaq M., Chung S., Fry W., Goldkorn T. Neutral sphingomyelinase 2 activity and protein stability are modulated by phosphorylation of five conserved serines. JBiol Chem 2012, 287:514-522.
42. Filosto S., Castillo S., Danielson A., Franzi L., Khan E., Kenyon N., et al. Neutral sphingomyelinase 2: a novel target in cigarette smoke-induced apoptosis and lung injury. Am J Respir Cell Mol Biol 2011, 44:350-360.
43. Filosto S., Fry W., Knowlton A.A., Goldkorn T. Neutral sphingomyelinase 2 (nSMase2) is a phosphoprotein regulated by calcineurin (PP2B). JBiol Chem 2010, 285:10213-10222.
44. Frazziano G., Moreno L., Moral-Sanz J., Menendez C., Escolano L., Gonzalez C., et al. Neutral sphingomyelinase, NADPH oxidase and reactive oxygen species. Role in acute hypoxic pulmonary vasoconstriction. JCell Physiol 2011, 226:2633-2640.
45. Galvani S., Trayssac M., Auge N., Thiers J.C., Calise D., Krell H.W., et al. Akey role for matrix metalloproteinases and neutral sphingomyelinase-2 in transplant vasculopathy triggered by anti-HLA antibody. Circulation 2011, 124:2725-2734.
46. Gills J.J., Zhang C., Abu-Asab M.S., Castillo S.S., Marceau C., LoPiccolo J., et al. Ceramide mediates nanovesicle shedding and cell death in response to phosphatidylinositol ether lipid analogs and perifosine. Cell Death Dis 2012, 3:e340.
47. Goldkorn T., Filosto S., Chung S. Lung injury and lung cancer caused by cigarette smoke-induced oxidative stress: molecular mechanisms and therapeutic opportunities involving the ceramide-generating machinery and epidermal growth factor receptor. Antioxid Redox Signal 2014, [Epub ahead of print].
48. Goni F.M., Alonso A. Sphingomyelinases: enzymology and membrane activity. FEBS Lett 2002, 531:38-46.
49. Grimm M.O., Grimm H.S., Patzold A.J., Zinser E.G., Halonen R., Duering M., et al. Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin. Nat Cell Biol 2005, 7:1118-1123.
50. Gu L., Huang B., Shen W., Gao L., Ding Z., Wu H., et al. Early activation of nSMase2/ceramide pathway in astrocytes is involved in ischemia-associated neuronal damage via inflammation in rat hippocampi. JNeuroinflam 2013, 10:109.
51. Haimovitz-Friedman A., Kan C.C., Ehleiter D., Persaud R.S., McLoughlin M., Fuks Z., et al. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. JExp Med 1994, 180:525-535.
52. Hannun Y.A., Obeid L.M. Many ceramides. JBiol Chem 2011, 286:27855-27862.
53. He Q., Wang G., Wakade S., Dasgupta S., Dinkins M., Kong J.N., et al. Primary cilia in stem cells and neural progenitors are regulated by neutral sphingomyelinase 2 and ceramide. Mol Biol Cell 2014, 25:1715-1729.
54. Henry B., Moller C., Dimanche-Boitrel M.T., Gulbins E., Becker K.A. Targeting the ceramide system in cancer. Cancer Lett 2013, 332:286-294.
55. Hernandez O.M., Discher D.J., Bishopric N.H., Webster K.A. Rapid activation of neutral sphingomyelinase by hypoxia-reoxygenation of cardiac myocytes. Circ Res 2000, 86:198-204.
56. Hinkovska-Galcheva V., Kjeldsen L., Mansfield P.J., Boxer L.A., Shayman J.A., Suchard S.J. Activation of a plasma membrane-associated neutral sphingomyelinase and concomitant ceramide accumulation during IgG-dependent phagocytosis in human polymorphonuclear leukocytes. Blood 1998, 91:4761-4769.
57. Hofmann K., Tomiuk S., Wolff G., Stoffel W. Cloning and characterization of the mammalian brain-specific, Mg2+-dependent neutral sphingomyelinase. Proc Natl Acad Sci U S A 2000, 97:5895-5900.
58. Hsieh C.Y., Hsu M.J., Hsiao G., Wang Y.H., Huang C.W., Chen S.W., et al. Andrographolide enhances nuclear factor-kappaB subunit p65 Ser536 dephosphorylation through activation of protein phosphatase 2A in vascular smooth muscle cells. JBiol Chem 2011, 286:5942-5955.
59. Huseby M., Shi K., Brown C.K., Digre J., Mengistu F., Seo K.S., et al. Structure and biological activities of beta toxin from Staphylococcus aureus. JBacteriol 2007, 189:8719-8726.
60. Ito H., Murakami M., Furuhata A., Gao S., Yoshida K., Sobue S., et al. Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin. Biochim Biophys Acta 2009, 1789:681-690.
61. Ito H., Tanaka K., Hagiwara K., Kobayashi M., Hoshikawa A., Mizutani N., et al. Transcriptional regulation of neutral sphingomyelinase 2 in all-trans retinoic acid-treated human breast cancer cell line, MCF-7. JBiochem 2012, 151:599-610.
62. Jana A., Pahan K. Oxidative stress kills human primary oligodendrocytes via neutral sphingomyelinase: implications for multiple sclerosis. JNeuroimmune Pharmacol: Off J Soc NeuroImmune Pharmacol 2007, 2:184-193.
63. Jarvis W.D., Kolesnick R.N., Fornari F.A., Traylor R.S., Gewirtz D.A., Grant S. Induction of apoptotic DNA damage and cell death by activation of the sphingomyelin pathway. Proc Natl Acad Sci U S A 1994, 91:73-77.
64. Ju T.C., Chen S.D., Liu C.C., Yang D.I. Protective effects of S-nitrosoglutathione against amyloid beta-peptide neurotoxicity. Free Radic Biol Med 2005, 38:938-949.
65. Kajimoto T., Ohmori S., Shirai Y., Sakai N., Saito N. Subtype-specific translocation of the delta subtype of protein kinase C and its activation by tyrosine phosphorylation induced by ceramide in HeLa cells. Mol Cell Biol 2001, 21:1769-1783.
66. Kakoi H., Maeda S., Shinohara N., Matsuyama K., Imamura K., Kawamura I., et al. Bone morphogenic protein (BMP) signaling up-regulates neutral sphingomyelinase 2 to suppress chondrocyte maturation via the Akt protein signaling pathway as a negative feedback mechanism. JBiol Chem 2014, 289:8135-8150.
67. Karakashian A.A., Giltiay N.V., Smith G.M., Nikolova-Karakashian M.N. Expression of neutral sphingomyelinase-2 (NSMase-2) in primary rat hepatocytes modulates IL-beta-induced JNK activation. FASEB J Off Publ Fed Am Soc Exp Biol 2004, 18:968-970.
68. Khavandgar Z., Poirier C., Clarke C.J., Li J., Wang N., McKee M.D., et al. Acell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization. JCell Biol 2011, 194:277-289.
69. Kim M.Y., Linardic C., Obeid L., Hannun Y. Identification of sphingomyelin turnover as an effector mechanism for the action of tumor necrosis factor alpha and gamma-interferon. Specific role in cell differentiation. JBiol Chem 1991, 266:484-489.
70. Kim S.K., Ahn K.H., Ji J.E., Choi J.M., Jeon H.J., Jung S.Y., et al. Neutral sphingomyelinase 2 induces dopamine uptake through regulation of intracellular calcium. Cell Signal 2010, 22:865-870.
71. Kim W.J., Okimoto R.A., Purton L.E., Goodwin M., Haserlat S.M., Dayyani F., et al. Mutations in the neutral sphingomyelinase gene SMPD3 implicate the ceramide pathway in human leukemias. Blood 2008, 111:4716-4722.
72. Kolmakova A., Kwiterovich P., Virgil D., Alaupovic P., Knight-Gibson C., Martin S.F., et al. Apolipoprotein C-I induces apoptosis in human aortic smooth muscle cells via recruiting neutral sphingomyelinase. Arterioscler Thromb Vasc Biol 2004, 24:264-269.
73. Kosaka N., Iguchi H., Hagiwara K., Yoshioka Y., Takeshita F., Ochiya T. Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. JBiol Chem 2013, 288:10849-10859.
74. Kosaka N., Iguchi H., Yoshioka Y., Takeshita F., Matsuki Y., Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. JBiol Chem 2010, 285:17442-17452.
75. Lei X., Bone R.N., Ali T., Wohltmann M., Gai Y., Goodwin K.J., et al. Genetic modulation of islet beta-cell iPLA(2)beta expression provides evidence for its impact on beta-cell apoptosis and autophagy. Islets 2013, 5:29-44.
76. Lei X., Zhang S., Barbour S.E., Bohrer A., Ford E.L., Koizumi A., et al. Spontaneous development of endoplasmic reticulum stress that can lead to diabetes mellitus is associated with higher calcium-independent phospholipase A2 expression: a role for regulation by SREBP-1. JBiol Chem 2010, 285:6693-6705.
77. Lei X., Zhang S., Bohrer A., Barbour S.E., Ramanadham S. Role of calcium-independent phospholipase A(2)beta in human pancreatic islet beta-cell apoptosis. Am J Physiol Endocrinol Metabol 2012, 303:E1386-E1395.
78. Levy M., Khan E., Careaga M., Goldkorn T. Neutral sphingomyelinase 2 is activated by cigarette smoke to augment ceramide-induced apoptosis in lung cell death. Am J Physiol Lung Cell Mol Physiol 2009, 297:L125-L133.
79. Lin W.C., Lin C.F., Chen C.L., Chen C.W., Lin Y.S. Inhibition of neutrophil apoptosis via sphingolipid signaling in acute lung injury. JPharmacol Exp Ther 2011, 339:45-53.
80. 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. JBiol Chem 1998, 273:11313-11320.
81. Liu B., Hassler D.F., Smith G.K., Weaver K., Hannun Y.A. Purification and characterization of a membrane bound neutral pH optimum magnesium-dependent and phosphatidylserine-stimulated sphingomyelinase from rat brain. JBiol Chem 1998, 273:34472-34479.
82. Luberto C., Hassler D.F., Signorelli P., Okamoto Y., Sawai H., Boros E., et al. Inhibition of tumor necrosis factor-induced cell death in MCF7 by a novel inhibitor of neutral sphingomyelinase. JBiol Chem 2002, 277:41128-41139.
83. Maddens S., Charruyer A., Plo I., Dubreuil P., Berger S., Salles B., et al. Kit signaling inhibits the sphingomyelin-ceramide pathway through PLC gamma 1: implication in stem cell factor radioprotective effect. Blood 2002, 100:1294-1301.
84. Marchesini N., Jones J.A., Hannun Y.A. Confluence induced threonine41/serine45 phospho-beta-catenin dephosphorylation via ceramide-mediated activation of PP1cgamma. Biochim Biophys Acta 2007, 1771:1418-1428.
85. Marchesini N., Luberto C., Hannun Y.A. Biochemical properties of mammalian neutral sphingomyelinase 2 and its role in sphingolipid metabolism. JBiol Chem 2003, 278:13775-13783.
86. Marchesini N., Osta W., Bielawski J., Luberto C., Obeid L.M., Hannun Y.A. Role for mammalian neutral sphingomyelinase 2 in confluence-induced growth arrest of MCF7 cells. JBiol Chem 2004, 279:25101-25111.
87. Matsuo Y., Yamada A., Tsukamoto K., Tamura H., Ikezawa H., Nakamura H., et al. Adistant evolutionary relationship between bacterial sphingomyelinase and mammalian DNase I. Protein Sci Publ Protein Soc 1996, 5:2459-2467.
88. Maupas-Schwalm F., Bedel A., Auge N., Grazide M.H., Mucher E., Thiers J.C., et al. Integrin alpha(v)beta(3), metalloproteinases, and sphingomyelinase-2 mediate urokinase mitogenic effect. Cell Signal 2009, 21:1925-1934.
89. Meyers-Needham M., Lewis J.A., Gencer S., Sentelle R.D., Saddoughi S.A., Clarke C.J., et al. Off-target function of the Sonic hedgehog inhibitor cyclopamine in mediating apoptosis via nitric oxide-dependent neutral sphingomyelinase 2/ceramide induction. Mol Cancer Ther 2012, 11:1092-1102.
90. Mikati M.A., Zeinieh M., Habib R.A., El Hokayem J., Rahmeh A., El Sabban M., et al. Changes in sphingomyelinases, ceramide, Bax, Bcl(2), and caspase-3 during and after experimental status epilepticus. Epilepsy Res 2008, 81:161-166.
91. Milhas D., Clarke C.J., Idkowiak-Baldys J., Canals D., Hannun Y.A. Anterograde and retrograde transport of neutral sphingomyelinase-2 between the Golgi and the plasma membrane. Biochim Biophys Acta 2010, 1801:1361-1374.
92. Mittelbrunn M., Gutierrez-Vazquez C., Villarroya-Beltri C., Gonzalez S., Sanchez-Cabo F., Gonzalez M.A., et al. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun 2011, 2:282.
93. Miura Y., Gotoh E., Nara F., Nishijima M., Hanada K. Hydrolysis of sphingosylphosphocholine by neutral sphingomyelinases. FEBS Lett 2004, 557:288-292.
94. Mogami K., Kishi H., Kobayashi S. Sphingomyelinase causes endothelium-dependent vasorelaxation through endothelial nitric oxide production without cytosolic Ca(2+) elevation. FEBS Lett 2005, 579:393-397.
95. Mondal S., Mandal C., Sangwan R., Chandra S., Mandal C. Withanolide D induces apoptosis in leukemia by targeting the activation of neutral sphingomyelinase-ceramide cascade mediated by synergistic activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. Mol Cancer 2010, 9:239.
96. Nalivaeva N.N., Rybakina E.G., Pivanovich I., Kozinets I.A., Shanin S.N., Bartfai T. Activation of neutral sphingomyelinase by IL-1beta requires the type 1 interleukin 1 receptor. Cytokine 2000, 12:229-232.
97. 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. JAntibiot 1999, 52:525-530.
98. Nara F., Tanaka M., Masuda-Inoue S., Yamasato Y., Doi-Yoshioka H., Suzuki-Konagai K., et al. Biological activities of scyphostatin, a neutral sphingomyelinase inhibitor from a discomycete, Trichopeziza mollissima. JAntibiot 1999, 52:531-535.
99. Nikolova-Karakashian M., Morgan E.T., Alexander C., Liotta D.C., Merrill A.H. Bimodal regulation of ceramidase by interleukin-1beta. Implications for the regulation of cytochrome p450 2C11. JBiol Chem 1997, 272:18718-18724.
100. Obeid L.M., Linardic C.M., Karolak L.A., Hannun Y.A. Programmed cell death induced by ceramide. Science 1993, 259:1769-1771.
101. Ogretmen B., Hannun Y.A. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer 2004, 4:604-616.
102. 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, 264:19076-19080.
103. Okazaki T., Bielawska A., Bell R.M., Hannun Y.A. Role of ceramide as a lipid mediator of 1 alpha, 25-dihydroxyvitamin D3-induced HL-60 cell differentiation. J Biol Chem 1990, 265:15823-15831.
104. Ohanian J., Forman S.P., Katzenberg G., Ohanian V. Endothelin-1 stimulates small artery VCAM-1 expression through p38MAPK-dependent neutral sphingomyelinase. JVasc Res 2012, 49:353-362.
105. Ohanian J., Liao A., Forman S.P., Ohanian V. Age-related remodeling of small arteries is accompanied by increased sphingomyelinase activity and accumulation of long-chain ceramides. Physiol Rep 2014, 2.
106. Openshaw A.E., Race P.R., Monzo H.J., Vazquez-Boland J.A., Banfield M.J. Crystal structure of SmcL, a bacterial neutral sphingomyelinase C from Listeria. JBiol Chem 2005, 280:35011-35017.
107. Park B., Lee Y.M., Kim J.S., Her Y., Kang J.H., Oh S.H., et al. Neutral sphingomyelinase 2 modulates cytotoxic effects of protopanaxadiol on different human cancer cells. BMC Complement Altern Med 2013, 13:194.
108. Pascual M., Valles S.L., Renau-Piqueras J., Guerri C. Ceramide pathways modulate ethanol-induced cell death in astrocytes. JNeurochem 2003, 87:1535-1545.
109. Pehar M., Vargas M.R., Robinson K.M., Cassina P., Diaz-Amarilla P.J., Hagen T.M., et al. Mitochondrial superoxide production and nuclear factor erythroid 2-related factor 2 activation in p75 neurotrophin receptor-induced motor neuron apoptosis. JNeurosci Off J Soc Neurosci 2007, 27:7777-7785.
110. Peng C.H., Huang C.N., Hsu S.P., Wang C.J. Penta-acetyl geniposide induce apoptosis in C6 glioma cells by modulating the activation of neutral sphingomyelinase-induced p75 nerve growth factor receptor and protein kinase Cdelta pathway. Mol Pharmacol 2006, 70:997-1004.
111. Philipp S., Puchert M., Adam-Klages S., Tchikov V., Winoto-Morbach S., Mathieu S., et al. The polycomb group protein EED couples TNF receptor 1 to neutral sphingomyelinase. Proc Natl Acad Sci U S A 2010, 107:1112-1117.
112. Phuyal S., Hessvik N.P., Skotland T., Sandvig K., Llorente A. Regulation of exosome release by glycosphingolipids and flotillins. FEBS J 2014, 281:2214-2227.
113. Plo I., Lautier D., Casteran N., Dubreuil P., Arock M., Laurent G. Kit signaling and negative regulation of daunorubicin-induced apoptosis: role of phospholipase Cgamma. Oncogene 2001, 20:6752-6763.
114. Poirier C., Berdyshev E.V., Dimitropoulou C., Bogatcheva N.V., Biddinger P.W., Verin A.D. Neutral sphingomyelinase 2 deficiency is associated with lung anomalies similar to emphysema. Mamm Genome Off J Int Mamm Genome Soc 2012, 23:758-763.
115. Qin J., Berdyshev E., Poirer C., Schwartz N.B., Dawson G. Neutral sphingomyelinase 2 deficiency increases hyaluronan synthesis by up-regulation of hyaluronan synthase 2 through decreased ceramide production and activation of Akt. JBiol Chem 2012, 287:13620-13632.
116. Qin J., Testai F.D., Dawson S., Kilkus J., Dawson G. Oxidized phosphatidylcholine formation and action in oligodendrocytes. JNeurochem 2009, 110:1388-1399.
117. Revill K., Wang T., Lachenmayer A., Kojima K., Harrington A., Li J., et al. Genome-wide methylation analysis and epigenetic unmasking identify tumor suppressor genes in hepatocellular carcinoma. Gastroenterology 2013, 145:1424-1435. e1-25.
118. Rutkute K., Asmis R.H., Nikolova-Karakashian M.N. Regulation of neutral sphingomyelinase-2 by GSH: a new insight to the role of oxidative stress in aging-associated inflammation. JLipid Res 2007, 48:2443-2452.
119. Rutkute K., Karakashian A.A., Giltiay N.V., Dobierzewska A., Nikolova-Karakashian M.N. Aging in rat causes hepatic hyperresponsiveness to interleukin-1beta which is mediated by neutral sphingomyelinase-2. Hepatology 2007, 46:1166-1176.
120. Sawada M., Nakashima S., Banno Y., Yamakawa H., Takenaka K., Shinoda J., et al. Influence of Bax or Bcl-2 overexpression on the ceramide-dependent apoptotic pathway in glioma cells. Oncogene 2000, 19:3508-3520.
121. Shah N.C., Shah G.J., Li Z., Jiang X.C., Altura B.T., Altura B.M. Short-term magnesium deficiency downregulates telomerase, upregulates neutral sphingomyelinase and induces oxidative DNA damage in cardiovascular tissues: relevance to atherogenesis, cardiovascular diseases and aging. Int J Clin Exp Med 2014, 7:497-514.
122. Sitrin R.G., Sassanella T.M., Petty H.R. An obligate role for membrane-associated neutral sphingomyelinase activity in orienting chemotactic migration of human neutrophils. Am J Respir Cell Mol Biol 2011, 44:205-212.
123. Skowronski E.W., Kolesnick R.N., Green D.R. Fas-mediated apoptosis and sphingomyelinase signal transduction: the role of ceramide as a second messenger for apoptosis. Cell Death Differ 1996, 3:171-176.
124. Smith A.R., Visioli F., Frei B., Hagen T.M. Age-related changes in endothelial nitric oxide synthase phosphorylation and nitric oxide dependent vasodilation: evidence for a novel mechanism involving sphingomyelinase and ceramide-activated phosphatase 2A. Aging Cell 2006, 5:391-400.
125. Soans E., Evans S.C., Cipolla C., Fernandes E. Characterizing the sphingomyelinase pathway triggered by PRIMA-1 derivatives in lung cancer cells with differing p53 status. Anticancer Res 2014, 34:3271-3283.
126. Somenzi G., Sala G., Rossetti S., Ren M., Ghidoni R., Sacchi N. Disruption of retinoic acid receptor alpha reveals the growth promoter face of retinoic acid. PLoS One 2007, 2:e836.
127. 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 U S A 2005, 102:4554-4559.
128. Strum J.C., Small G.W., Pauig S.B., Daniel L.W. 1-beta-d-Arabinofuranosylcytosine stimulates ceramide and diglyceride formation in HL-60 cells. JBiol Chem 1994, 269:15493-15497.
129. Sumitomo M., Ohba M., Asakuma J., Asano T., Kuroki T., Asano T., et al. Protein kinase Cdelta amplifies ceramide formation via mitochondrial signaling in prostate cancer cells. JClin Investig 2002, 109:827-836.
130. Szabo G., Csak T. Inflammasomes in liver diseases. JHepatol 2012, 57:642-654.
131. Tabatadze N., Savonenko A., Song H., Bandaru V.V., Chu M., Haughey N.J. Inhibition of neutral sphingomyelinase-2 perturbs brain sphingolipid balance and spatial memory in mice. JNeurosci Res 2010, 88:2940-2951.
132. Takeda Y., Tashima M., Takahashi A., Uchiyama T., Okazaki T. Ceramide generation in nitric oxide-induced apoptosis. Activation of magnesium-dependent neutral sphingomyelinase via caspase-3. JBiol Chem 1999, 274:10654-10660.
133. Tamiya-Koizumi K., Kojima K. Activation of magnesium-dependent, neutral sphingomyelinase by phosphatidylserine. JBiochem 1986, 99:1803-1806.
134. Tanabe F., Nakajima T., Ito M. Involvement of diacylglycerol produced by phospholipase D activation in Abeta-induced reduction of sAPPalpha secretion in SH-SY5Y neuroblastoma cells. Biochem Biophys Res Commun 2014, 446:933-939.
135. Tani M., Hannun Y.A. Analysis of membrane topology of neutral sphingomyelinase 2. FEBS Lett 2007, 581:1323-1328.
136. Tani M., Hannun Y.A. Neutral sphingomyelinase 2 is palmitoylated on multiple cysteine residues. Role of palmitoylation in subcellular localization. JBiol Chem 2007, 282:10047-10056.
137. Tcherkasowa A.E., Adam-Klages S., Kruse M.L., Wiegmann K., Mathieu S., Kolanus W., et al. Interaction with factor associated with neutral sphingomyelinase activation, a WD motif-containing protein, identifies receptor for activated C-kinase 1 as a novel component of the signaling pathways of the p55 TNF receptor. JImmunol 2002, 169:5161-5170.
138. Tellier E., Negre-Salvayre A., Bocquet B., Itohara S., Hannun Y.A., Salvayre R., et al. Role for furin in tumor necrosis factor alpha-induced activation of the matrix metalloproteinase/sphingolipid mitogenic pathway. Mol Cell Biol 2007, 27:2997-3007.
139. Tepper C.G., Jayadev S., Liu B., Bielawska A., Wolff R., Yonehara S., et al. Role of ceramide as an endogenous mediator of Fas-induced cytotoxicity. Proc Natl Acad Sci USA 1995, 92:8443-8447.
140. Thery C., Zitvogel L., Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002, 2:569-579.
141. Tomiuk S., Zumbansen M., Stoffel W. Characterization and subcellular localization of murine and human magnesium-dependent neutral sphingomyelinase. JBiol Chem 2000, 275:5710-5717.
142. Tsai C.C., Kai J.I., Huang W.C., Wang C.Y., Wang Y., Chen C.L., et al. Glycogen synthase kinase-3beta facilitates IFN-gamma-induced STAT1 activation by regulating Src homology-2 domain-containing phosphatase 2. JImmunol 2009, 183:856-864.
143. Tsakiri N., Kimber I., Rothwell N.J., Pinteaux E. Interleukin-1-induced interleukin-6 synthesis is mediated by the neutral sphingomyelinase/Src kinase pathway in neurones. Br J Pharmacol 2008, 153:775-783.
144. Wang G., Dinkins M., He Q., Zhu G., Poirier C., Campbell A., et al. Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4): potential mechanism of apoptosis induction in Alzheimer disease (AD). JBiol Chem 2012, 287:21384-21395.
145. Wheeler D., Knapp E., Bandaru V.V., Wang Y., Knorr D., Poirier C., et al. Tumor necrosis factor-alpha-induced neutral sphingomyelinase-2 modulates synaptic plasticity by controlling the membrane insertion of NMDA receptors. JNeurochem 2009, 109:1237-1249.
146. Wiesner D.A., Kilkus J.P., Gottschalk A.R., Quintans J., Dawson G. Anti-immunoglobulin-induced apoptosis in WEHI 231 cells involves the slow formation of ceramide from sphingomyelin and is blocked by bcl-XL. JBiol Chem 1997, 272:9868-9876.
147. Wu B.X., Clarke C.J., Hannun Y.A. Mammalian neutral sphingomyelinases: regulation and roles in cell signaling responses. Neuromol Med 2010, 12:320-330.
148. Wu B.X., Clarke C.J., Matmati N., Montefusco D., Bartke N., Hannun Y.A. Identification of novel anionic phospholipid binding domains in neutral sphingomyelinase 2 with selective binding preference. JBiol Chem 2011, 286:22362-22371.
149. Yang Z., Costanzo M., Golde D.W., Kolesnick R.N. Tumor necrosis factor activation of the sphingomyelin pathway signals nuclear factor kappa B translocation in intact HL-60 cells. JBiol Chem 1993, 268:20520-20523.
150. Yoshimura S., Banno Y., Nakashima S., Hayashi K., Yamakawa H., Sawada M., et al. Inhibition of neutral sphingomyelinase activation and ceramide formation by glutathione in hypoxic PC12 cell death. JNeurochem 1999, 73:675-683.
151. Yoshimura S., Banno Y., Nakashima S., Takenaka K., Sakai H., Nishimura Y., et al. Ceramide formation leads to caspase-3 activation during hypoxic PC12 cell death. Inhibitory effects of Bcl-2 on ceramide formation and caspase-3 activation. JBiol Chem 1998, 273:6921-6927.
152. Yuyama K., Sun H., Mitsutake S., Igarashi Y. Sphingolipid-modulated exosome secretion promotes clearance of amyloid-beta by microglia. JBiol Chem 2012, 287:10977-10989.
153. Zeeck A., Schroder K., Frobel K., Grote R., Thiericke R. The structure of manumycin. I. Characterization, structure elucidation and biological activity. JAntibiot 1987, 40:1530-1540.
154. Zhang P., Liu B., Jenkins G.M., Hannun Y.A., Obeid L.M. Expression of neutral sphingomyelinase identifies a distinct pool of sphingomyelin involved in apoptosis. JBiol Chem 1997, 272:9609-9612.
155. Zhang Y.H., Vasko M.R., Nicol G.D. Ceramide, a putative second messenger for nerve growth factor, modulates the TTX-resistant Na(+) current and delayed rectifier K(+) current in rat sensory neurons. JPhysiol 2002, 544:385-402.