• 1
    Bajt M, Farhood A, Jaeschke H. Effects of CXC chemokines on neutrophil activation and sequestration in hepatic vasculature. Am J Physiol Gastrointest Liver Physiol 2001; 281: G1188G1195.
  • 2
    Zwacka RM, Zhang Y, Halldorson J, Schlossberg H, Dudus L, Engelhardt JF. CD4(+) T-lymphocytes mediate ischemia/reperfusion-induced inflammatory responses in mouse liver. J Clin Invest 1997; 100: 279289.
  • 3
    Caldwell-Kenkel JC, Currin RT, Tanaka Y, Thurman RG, Lemasters JJ. Kupffer cell activation and endothelial cell damage after storage of rat livers: effects of reperfusion. Hepatology 1991; 13: 8395.
  • 4
    Luedde T, Assmus U, Wustefeld T, Meyer zu Vilsendorf A, Roskams T, Schmidt-Supprian M, et al. Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury. J Clin Invest 2005; 115: 849859.
  • 5
    Colletti LM, Remick DG, Burtch GD, Kunkel SL, Strieter RM, Campbell DA Jr. Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. J Clin Invest 1990; 85: 19361943.
  • 6
    Rudiger HA, Clavien PA. Tumor necrosis factor alpha, but not Fas, mediates hepatocellular apoptosis in the murine ischemic liver. Gastroenterology 2002; 122: 202210.
  • 7
    Uehara T, Bennett B, Sakata ST, Satoh Y, Bilter GK, Westwick JK, et al. JNK mediates hepatic ischemia reperfusion injury. J Hepatol 2005; 42: 850859.
  • 8
    Jaeschke H, Lemasters JJ. Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury. Gastroenterology 2003; 125: 12461257.
  • 9
    Hannun YA, Luberto C. Ceramide in the eukaryotic stress response. Trends Cell Biol 2000; 10: 7380.
  • 10
    Garcia-Ruiz C, Colell A, Mari M, Morales A, Fernandez-Checa JC. Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species: role of mitochondrial glutathione. J Biol Chem 1997; 272: 1136911377.
  • 11
    Kolesnick RN, Kronke M. Regulation of ceramide production and apoptosis. Annu Rev Physiol 1998; 60: 643665.
  • 12
    Scarlatti F, Bauvy C, Ventruti A, Sala G, Cluzeaud F, Vandewalle A, et al. Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1. J Biol Chem 2004; 279: 1838418391.
  • 13
    Merrill AH Jr. De novo sphingolipid biosynthesis: a necessary, but dangerous, pathway. J Biol Chem 2002; 277: 2584325846.
  • 14
    Cremesti AE, Goni FM, Kolesnick R. Role of sphingomyelinase and ceramide in modulating rafts: do biophysical properties determine biologic outcome? FEBS Lett 2002; 531: 4753.
  • 15
    Paris F, Grassme H, Cremesti A, Zager J, Fong Y, Haimovitz-Friedman A, et al. Natural ceramide reverses Fas resistance of acid sphingomyelinase(−/−) hepatocytes. J Biol Chem 2001: 276: 82978305.
  • 16
    Garcia-Ruiz C, Colell A, Mari M, Morales A, Calvo M, Enrich C, et al. Defective TNF-alpha-mediated hepatocellular apoptosis and liver damage in acidic sphingomyelinase knockout mice. J Clin Invest 2003; 111: 197208.
  • 17
    Ogretmen B, Hannun YA. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer 2004; 4: 604616.
  • 18
    Morita Y, Perez GI, Paris F, Miranda SR, Ehleiter D, Haimovitz-Friedman A, et al. Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. Nat Med 2000; 6: 11091114.
  • 19
    Morales A, Colell A, Mari M, Garcia-Ruiz C, Fernandez-Checa JC. Glycosphingolipids and mitochondria: role in apoptosis and disease. Glycoconj J 2004; 20: 579588.
  • 20
    Meng A, Luberto C, Meier P, Bai A, Yang X, Hannun YA, et al. Sphingomyelin synthase as a potential target for D609-induced apoptosis in U937 human monocytic leukemia cells. Exp Cell Res 2004; 292: 385392.
  • 21
    Strelow A, Bernardo K, Adam-Klages S, Linke T, Sandhoff K, Kronke M, et al. Overexpression of acid ceramidase protects from tumor necrosis factor-induced cell death. J Exp Med 2000; 192: 601612.
  • 22
    Maceyka M, Payne SG, Milstien S, Spiegel S. Sphingosine kinase, sphingosine-1-phosphate, and apoptosis. Biochim Biophys Acta 2002; 1585: 193201.
  • 23
    Teoh N, Field J, Sutton J, Farrell G. Dual role of tumor necrosis factor-alpha in hepatic ischemia-reperfusion injury: studies in tumor necrosis factor-alpha gene knockout mice. HEPATOLOGY 2004; 39: 412421.
  • 24
    Bradham CA, Stachlewitz RF, Gao W, Qian T, Jayadev S, Jenkins G, et al. Reperfusion after liver transplantation in rats differentially activates the mitogen-activated protein kinases. HEPATOLOGY 1997; 25: 11281135.
  • 25
    Alessenko AV, Galperin EI, Dudnik LB, Korobko VG, Mochalova ES, Platonova LV, et al. Role of tumor necrosis factor alpha and sphingomyelin cycle activation in the induction of apoptosis by ischemia/reperfusion of the liver. Biochemistry (Mosc) 2002; 67: 13471355.
  • 26
    Mari M, Colell A, Morales A, Paneda C, Varela-Nieto I, Garcia-Ruiz C, et al. Acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor-induced lethal hepatitis. J Clin Invest 2004; 113: 895904.
  • 27
    Garcia-Ruiz C, Mari M, Morales A, Colell A, Ardite E, Fernández-Checa JC. Human placenta sphingomyelinase, an exogenous acidic pH-optimum sphingomyelinase, induces oxidative stress, glutathione depletion, and apoptosis in rat hepatocytes. HEPATOLOGY 2000; 32: 5665.
  • 28
    Nikolova-Karakashian M, Morgan ET, Alexander C, Liotta DC, Merril AH Jr. Bimodal regulation of ceramidase by interleukin-1beta. Implications for the regulation of cytochrome p450 2C11. J Biol Chem 1997; 272: 1871818724.
  • 29
    Veldman RJ, Mitta A, Cuvillier O, Garcia V, Klappe K, Medin JA, et al. The absence of functional glucosylceramide synthase does not sensitize melanoma cells for anticancer drugs. FASEB J 2003; 17: 11441146.
  • 30
    Paris R, Morales A, Coll O, Sanchez-Reyes A, Garcia-Ruiz C, Fernandez-Checa JC. Ganglioside GD3 sensitizes human hepatoma cells to cancer therapy. J Biol Chem 2002; 277: 4987049876.
  • 31
    Song E, Lee SK, Wang, J, Ince N, Ouyang N, Min J, et al. RNA interference targeting Fas protects mice from fulminant hepatitis. Nat Med 2003; 9: 347351.
  • 32
    Zender L, Hutker S, Liedtke C, Tillmann HL, Zender S, Mundt B, et al. Caspase 8 small interfering RNA prevents acute liver failure in mice. Proc Natl Acad Sci U S A 2003; 100: 77977802.
  • 33
    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: 447450.
  • 34
    Sugita M, Willians M, Dulaney JT, Moser HW. Ceramidase and ceramide synthesis in human kidney and cerebellum: description of a new alkaline ceramidase. Biochim Biophys Acta 1975; 398: 12531.
  • 35
    Ikegami M, Dhami R, Schuchman EH. Alveolar lipoproteinosis in an acid sphingomyelinase-deficient mouse model of Niemann-Pick disease. Am J Physiol Lung Cell Mol Physiol 2003; 284: L518L525.
  • 36
    Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 2001; 413: 732738.
  • 37
    Heidel JD, Hu S, Liu XF, Triche TJ, Davis ME. Lack of interferon response in animals to naked siRNAs. Nat Biotechnol 2004; 22: 15791582.
  • 38
    Verheij M, Bose R, Lin XH, Yao B, Jarvis WD, Grant S, et al. Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 1996; 380: 7579.
  • 39
    Westwick JK, Bielawska AE, Dbaibo G, Hannun YA, Brenner DA. Ceramide activates the stress-activated protein kinases. J Biol Chem 1995; 270: 2268922692.
  • 40
    Kurinna SM, Tsao CC, Nica AF, Jiffar T, Ruvolo PP. Ceramide promotes apoptosis in lung cancer-derived A549 cells by a mechanism involving c-Jun NH2-terminal kinase. Cancer Res 2004; 64: 78527856.
  • 41
    Bennett BL, Sasaki DT, Murray BW, O'Leary EC, Sakata ST, Xu W, et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci U S A 2001; 98: 1368113686.
  • 42
    Schmidt-Choudhury A, Furuta G, Lavigne J, Galil S, Wershil B. The regulation of tumor necrosis factor-alpha production in murine mast cells: pentoxyfilline or dexamethasone inhibits IgE-dependent production of TNF-alpha by distinct mechanisms. Cell Immunol 1996; 171: 140146.
  • 43
    He X, Okino N, Dhami R, Dagan A, Gatt S, Schulze H, et al. Purification and characterization of recombinant, human acid ceramidase: catalytic reactions and interactions with acid sphingomyelinase. J Biol Chem 2003; 278: 3297832986.
  • 44
    Osawa Y, Uchinami H, Bielawski J, Schwabe RF, Hannun YA, Brenner DA. Roles for C16-ceramide and sphingosine 1-phosphate in regulating hepatocyte apoptosis in response to tumor necrosis factor-alpha. J Biol Chem 2005; 280: 2787927887.
  • 45
    Baine CP, Kaiser RA, Purcell NH, Blair NS, Osinka H, Hambleton MA, et al. Loss of cyclophilin D reveals a critical role of mitochondrial permeability transition in cell death. Nature 2005; 434: 658662.
  • 46
    Kagan VE, Tyurin VA, Jiang J, Tyurina YY, Ritov VB, Amoscato AA, et al. Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nat Chem Biol 2005; 1: 223232.
  • 47
    Gupta S, Natarajan R, Payne SG, Studer EJ, Spiegel S, Dent P, et al. Deoxycholic acid activates c-Jun N-terminal Kinase pathway via FAS receptor activation in primary hepatocytes. J Biol Chem 2004; 279: 58215828.
  • 48
    Aoki H, Kang PM, Hampe J, Yoshimura K, Noma T, Matsuzaki M, et al. Direct activation of mitochondrial apoptosis machinery by c-Jun N-terminal kinase in adult cardiac myocytes. J Biol Chem 2002; 277: 1024410250.
  • 49
    Kharbanda S, Saxena S, Yoshida K, Pandey P, Kaneki M, Wang O, et al. Translocation of SAPK/JNK to mitochondria and interaction with Bcl-xL in response to DNA damage. J Biol Chem 2000; 275: 322327.
  • 50
    Ley R, Ewings KE, Hadfield K, Cook SJ. Regulatory phosphorylation of Bim: sorting out the ERK from the JNK. Cell Death Differ 2005; 12: 10081014.