Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter March 12, 2015

Sphingolipids in liver injury, repair and regeneration

  • Hiroyuki Nojima , Christopher M. Freeman , Erich Gulbins and Alex B. Lentsch EMAIL logo
From the journal Biological Chemistry

Abstract

Sphingolipids are not only essential components of cellular membranes but also function as intracellular and extracellular mediators that regulate important physiological cellular processes including cell survival, proliferation, apoptosis, differentiation, migration and immune responses. The liver possesses the unique ability to regenerate after injury in a complex manner that involves numerous mediators, including sphingolipids such as ceramide and sphingosine 1-phosphate. Here we present the current understanding of the involvement of the sphingolipid pathway and the role this pathway plays in regulating liver injury, repair and regeneration. The regulation of sphingolipids and their enzymes may have a great impact in the development of novel therapeutic modalities for a variety of liver injuries and diseases.


Corresponding author: Alex B. Lentsch, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558, USA, e-mail:

References

Abu-Amara, M., Yang, S.Y., Tapuria, N., Fuller, B., Davidson, B., and Seifalian, A. (2010). Liver ischemia/reperfusion injury: processes in inflammatory networks – a review. Liver Transpl. 16, 1016–1032.10.1002/lt.22117Search in Google Scholar

Adachi, T., Nakashima, S., Saji, S., Nakamura, T., and Nozawa, Y. (1996). Mitogen-activated protein kinase activation in hepatocyte growth factor-stimulated rat hepatocytes: involvement of protein tyrosine kinase and protein kinase C. Hepatology 23, 1244–1253.10.1002/hep.510230545Search in Google Scholar

Albi, E., Peloso, I., and Magni, M.V. (1999). Nuclear membrane sphingomyelin-cholesterol changes in rat liver after hepatectomy. Biochem. Biophys. Res. Commun. 262, 692–695.10.1006/bbrc.1999.1188Search in Google Scholar

Albi, E., Rossi, G., Maraldi, N.M., Magni, M.V., Cataldi, S., Solimando, L., and Zini, N. (2003). Involvement of nuclear phosphatidylinositol-dependent phospholipases C in cell cycle progression during rat liver regeneration. J. Cell. Physiol. 197, 181–188.10.1002/jcp.10292Search in Google Scholar

Albi, E., Lazzarini, A., Lazzarini, R., Floridi, A., Damaskopoulou, E., Curcio, F., and Cataldi, S. (2013). Nuclear lipid microdomain as place of interaction between sphingomyelin and DNA during liver regeneration. Int. J. Mol. Sci. 14, 6529–6541.10.3390/ijms14046529Search in Google Scholar

Alessenko, A. and Chatterjee, S. (1995). Neutral sphingomyelinase: localization in rat liver nuclei and involvement in regeneration/proliferation. Mol. Cell. Biochem. 143, 169–174.10.1007/BF01816950Search in Google Scholar

Alessenko, A.V., Platonova, L.V., Sakevarashvili, G.R., Khrenov, A.V., Shingarova, L.N., Shono, N.I., and Galperin, E.I. (1999). Role of endogenous TNF-α and sphingosine in induced DNA synthesis in regenerating rat liver after partial hepatectomy. Biochemistry (Moscow) 64, 890–895.Search in Google Scholar

Alessenko, A.V., Galperin, E.I., Dudnik, L.B., Korobko, V.G., Mochalova, E.S., Platonova, L.V., Shingarova, L.N., Shono, N.I., and Shupik, M.A. (2002). Role of tumor necrosis factor α and sphingomyelin cycle activation in the induction of apoptosis by ischemia/reperfusion of the liver. Biochemistry (Moscow) 67, 1347–1355.10.1023/A:1021853825244Search in Google Scholar

Ali, M., Fritsch, J., Zigdon, H., Pewzner-Jung, Y., Schutze, S., and Futerman, A.H. (2013). Altering the sphingolipid acyl chain composition prevents LPS/GLN-mediated hepatic failure in mice by disrupting TNFR1 internalization. Cell Death Dis. 4, e929.10.1038/cddis.2013.451Search in Google Scholar

Arora, A.S., Jones, B.J., Patel, T.C., Bronk, S.F., and Gores, G.J. (1997). Ceramide induces hepatocyte cell death through disruption of mitochondrial function in the rat. Hepatology 25, 958–963.10.1002/hep.510250428Search in Google Scholar

Ballou, L.R., Chao, C.P., Holness, M.A., Barker, S.C., and Raghow, R. (1992). Interleukin–1-mediated PGE2 production and sphingomyelin metabolism. Evidence for the regulation of cyclooxygenase gene expression by sphingosine and ceramide. J. Biol. Chem. 267, 20044–20050.10.1016/S0021-9258(19)88663-5Search in Google Scholar

Barth, B.M., Shanmugavelandy, S.S., Kaiser, J.M., McGovern, C., Altinoglu, E.I., Haakenson, J.K., Hengst, J.A., Gilius, E.L., Knupp, S.A., Fox, T.E., et al. (2013). PhotoImmunoNanoTherapy reveals an anticancer role for sphingosine kinase 2 and dihydrosphingosine-1-phosphate. ACS Nano. 7, 2132–2144.10.1021/nn304862bSearch in Google Scholar

Bartke, N. and Hannun, Y.A. (2009). Bioactive sphingolipids: metabolism and function. J. Lipid Res. 50 (Suppl.), S91–S96.10.1194/jlr.R800080-JLR200Search in Google Scholar

Basnakian, A.G., Ueda, N., Hong, X., Galitovsky, V.E., Yin, X., and Shah, S.V. (2005). Ceramide synthase is essential for endonuclease-mediated death of renal tubular epithelial cells induced by hypoxia-reoxygenation. Am. J. Physiol. Renal Physiol. 288, F308–F314.10.1152/ajprenal.00204.2004Search in Google Scholar

Bataller, R. and Brenner, D.A. (2005). Liver fibrosis. J. Clin. Invest. 115, 209–218.10.1172/JCI24282Search in Google Scholar

Belghiti, J., Noun, R., Zante, E., Ballet, T., and Sauvanet, A. (1996). Portal triad clamping or hepatic vascular exclusion for major liver resection. A controlled study. Ann. Surg. 224, 155–161.10.1097/00000658-199608000-00007Search in Google Scholar

Bernal, W., Auzinger, G., Dhawan, A., and Wendon, J. (2010). Acute liver failure. Lancet 376, 190–201.10.1016/S0140-6736(10)60274-7Search in Google Scholar

Bollinger, C.R., Teichgraber, V., and Gulbins, E. (2005). Ceramide-enriched membrane domains. Biochim. Biophys. Acta 1746, 284–294.10.1016/j.bbamcr.2005.09.001Search in Google Scholar PubMed

Bradham, C.A., Stachlewitz, R.F., Gao, W., Qian, T., Jayadev, S., Jenkins, G., Hannun, Y., Lemasters, J.J., Thurman, R.G., and Brenner, D.A. (1997). Reperfusion after liver transplantation in rats differentially activates the mitogen-activated protein kinases. Hepatology 25, 1128–1135.10.1002/hep.510250514Search in Google Scholar PubMed

Brown, R.E. (1998). Sphingolipid organization in biomembranes: what physical studies of model membranes reveal. J. Cell. Sci. 111, 1–9.10.1242/jcs.111.1.1Search in Google Scholar PubMed PubMed Central

Canbay, A., Friedman, S., and Gores, G.J. (2004). Apoptosis: the nexus of liver injury and fibrosis. Hepatology 39, 273–278.10.1002/hep.20051Search in Google Scholar PubMed

Chatzakos, V., Rundlof, A.K., Ahmed, D., de Verdier, P.J., and Flygare, J. (2012). Inhibition of sphingosine kinase 1 enhances cytotoxicity, ceramide levels and ROS formation in liver cancer cells treated with selenite. Biochem. Pharmacol. 84, 712–721.10.1016/j.bcp.2012.06.009Search in Google Scholar

Chen, J., Nikolova-Karakashian, M., Merrill, A.H., Jr., and Morgan, E.T. (1995). Regulation of cytochrome P450 2C11 (CYP2C11) gene expression by interleukin-1, sphingomyelin hydrolysis, and ceramides in rat hepatocytes. J. Biol. Chem. 270, 25233–25238.10.1074/jbc.270.42.25233Search in Google Scholar

Colletti, L.M., Remick, D.G., Burtch, G.D., Kunkel, S.L., Strieter, R.M., and Campbell, D.A., Jr. (1990). Role of tumor necrosis factor-α in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. J. Clin. Invest. 85, 1936–1943.10.1172/JCI114656Search in Google Scholar

Coutant, A., Rescan, C., Gilot, D., Loyer, P., Guguen-Guillouzo, C., and Baffet, G. (2002). PI3K-FRAP/mTOR pathway is critical for hepatocyte proliferation whereas MEK/ERK supports both proliferation and survival. Hepatology 36, 1079–1088.10.1053/jhep.2002.36160Search in Google Scholar

Cuvillier, O., Pirianov, G., Kleuser, B., Vanek, P.G., Coso, O.A., Gutkind, S., and Spiegel, S. (1996). Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Nature 381, 800–803.10.1038/381800a0Search in Google Scholar

Cuzzocrea, S., Di Paola, R., Genovese, T., Mazzon, E., Esposito, E., Crisafulli, C., Bramanti, P., and Salvemini, D. (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, 45–57.10.1124/jpet.108.139808Search in Google Scholar

Davaille, J., Li, L., Mallat, A., and Lotersztajn, S. (2002). Sphingosine 1-phosphate triggers both apoptotic and survival signals for human hepatic myofibroblasts. J. Biol. Chem. 277, 37323–37330.10.1074/jbc.M202798200Search in Google Scholar

Dawson, T.C., Lentsch, A.B., Wang, Z., Cowhig, J.E., Rot, A., Maeda, N., and Peiper, S.C. (2000). Exaggerated response to endotoxin in mice lacking the Duffy antigen/receptor for chemokines (DARC). Blood 96, 1681–1684.10.1182/blood.V96.5.1681Search in Google Scholar

Dbaibo, G.S., Obeid, L.M., and Hannun, Y.A. (1993). Tumor necrosis factor-α (TNF-α) signal transduction through ceramide. Dissociation of growth inhibitory effects of TNF-α from activation of nuclear factor-κB. J. Biol. Chem. 268, 17762–17766.10.1016/S0021-9258(17)46770-6Search in Google Scholar

Donati, C., Cencetti, F., Nincheri, P., Bernacchioni, C., Brunelli, S., Clementi, E., Cossu, G., and Bruni, P. (2007). Sphingosine 1-phosphate mediates proliferation and survival of mesoangioblasts. Stem Cells 25, 1713–1719.10.1634/stemcells.2006-0725Search in Google Scholar PubMed

Fausto, N., Campbell, J.S., and Riehle, K.J. (2006). Liver regeneration. Hepatology 43, S45–53.10.1002/hep.20969Search in Google Scholar

Frago, L.M., Paneda, C., Fabregat, I., and Varela-Nieto, I. (2001). Short-chain ceramide regulates hepatic methionine adenosyltransferase expression. J. Hepatol. 34, 192–201.10.1016/S0168-8278(00)00022-2Search in Google Scholar

Futerman, A.H. and Riezman, H. (2005). The ins and outs of sphingolipid synthesis. Trends Cell. Biol. 15, 312–318.10.1016/j.tcb.2005.04.006Search in Google Scholar

Garcia-Ruiz, C., Colell, A., Mari, M., Morales, A., Calvo, M., Enrich, C., and Fernandez-Checa, J.C. (2003). Defective TNF-α-mediated hepatocellular apoptosis and liver damage in acidic sphingomyelinase knockout mice. J. Clin. Invest. 111, 197–208.10.1172/JCI16010Search in Google Scholar

Grassme, H., Jekle, A., Riehle, A., Schwarz, H., Berger, J., Sandhoff, K., Kolesnick, R., and Gulbins, E. (2001). CD95 signaling via ceramide-rich membrane rafts. J. Biol. Chem. 276, 20589–20596.10.1074/jbc.M101207200Search in Google Scholar

Gulbins, E. and Kolesnick, R. (2003). Raft ceramide in molecular medicine. Oncogene 22, 7070–7077.10.1038/sj.onc.1207146Search in Google Scholar

Gulbins, E., Bissonnette, R., Mahboubi, A., Martin, S., Nishioka, W., Brunner, T., Baier, G., Baier-Bitterlich, G., Byrd, C., Lang, F., et al. (1995). FAS-induced apoptosis is mediated via a ceramide-initiated RAS signaling pathway. Immunity 2, 341–351.10.1016/1074-7613(95)90142-6Search in Google Scholar

Hannun, Y.A. and Bell, R.M. (1989). Functions of sphingolipids and sphingolipid breakdown products in cellular regulation. Science 243, 500–507.10.1126/science.2643164Search in Google Scholar PubMed

Hannun, Y.A. and Obeid, L.M. (2008). Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell. Biol. 9, 139–150.10.1038/nrm2329Search in Google Scholar PubMed

Hines, I.N., Harada, H., Flores, S., Gao, B., McCord, J.M., and Grisham, M.B. (2005). Endothelial nitric oxide synthase protects the post-ischemic liver: potential interactions with superoxide. Biomed. Pharmacother. 59, 183–189.10.1016/j.biopha.2005.03.011Search in Google Scholar PubMed

Hinson, J.A., Roberts, D.W., and James, L.P. (2010). Mechanisms of acetaminophen-induced liver necrosis. Handb. Exp. Pharmacol. 369–405.10.1007/978-3-642-00663-0_12Search in Google Scholar PubMed PubMed Central

Houmard, B.S., Guan, Z., Kim-Lee, M., Stokes, B.T., and Ottobre, J.S. (1991). The effects of elevation and depletion of intracellular free calcium on progesterone and prostaglandin production by the primate corpus luteum. Biol. Reprod. 45, 560–565.10.1095/biolreprod45.4.560Search in Google Scholar PubMed

Husted, T.L., Blanchard, J., Schuster, R., Shen, H., and Lentsch, A.B. (2006). Potential role for IL-23 in hepatic ischemia/reperfusion injury. Inflamm. Res. 55, 177–178.10.1007/s00011-006-0073-1Search in Google Scholar PubMed

Ichi, I., Nakahara, K., Fujii, K., Iida, C., Miyashita, Y., and Kojo, S. (2007). Increase of ceramide in the liver and plasma after carbon tetrachloride intoxication in the rat. J. Nutr. Sci. Vitaminol. (Tokyo) 53, 53–56.10.3177/jnsv.53.53Search in Google Scholar PubMed

Ikeda, H., Satoh, H., Yanase, M., Inoue, Y., Tomiya, T., Arai, M., Tejima, K., Nagashima, K., Maekawa, H., Yahagi, N., et al. (2003). Antiproliferative property of sphingosine 1-phosphate in rat hepatocytes involves activation of Rho via Edg-5. Gastroenterology 124, 459–469.10.1053/gast.2003.50049Search in Google Scholar PubMed

Ikeda, H., Watanabe, N., Ishii, I., Shimosawa, T., Kume, Y., Tomiya, T., Inoue, Y., Nishikawa, T., Ohtomo, N., Tanoue, Y., et al. (2009). Sphingosine 1-phosphate regulates regeneration and fibrosis after liver injury via sphingosine 1-phosphate receptor 2. J. Lipid Res. 50, 556–564.10.1194/jlr.M800496-JLR200Search in Google Scholar PubMed PubMed Central

Iwaisako, K., Jiang, C., Zhang, M., Cong, M., Moore-Morris, T.J., Park, T.J., Liu, X., Xu, J., Wang, P., Paik, Y.H., et al. (2014). Origin of myofibroblasts in the fibrotic liver in mice. Proc. Natl. Acad. Sci. USA 111, E3297–3305.10.1073/pnas.1400062111Search in Google Scholar PubMed PubMed Central

Jaeschke, H., Williams, C.D., Ramachandran, A., and Bajt, M.L. (2012). Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity. Liver Int. 32, 8–20.10.1111/j.1478-3231.2011.02501.xSearch in Google Scholar PubMed PubMed Central

Jenkins, G.M., Richards, A., Wahl, T., Mao, C., Obeid, L., and Hannun, Y. (1997). Involvement of yeast sphingolipids in the heat stress response of Saccharomyces cerevisiae. J. Biol. Chem. 272, 32566–32572.10.1074/jbc.272.51.32566Search in Google Scholar PubMed

Jin, J., Hou, Q., Mullen, T.D., Zeidan, Y.H., Bielawski, J., Kraveka, J.M., Bielawska, A., Obeid, L.M., Hannun, Y.A., and Hsu, Y.T. (2008). 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. 283, 26509–26517.10.1074/jbc.M801597200Search in Google Scholar PubMed PubMed Central

Jones, B.E., Lo, C.R., Srinivasan, A., Valentino, K.L., and Czaja, M.J. (1999). Ceramide induces caspase-independent apoptosis in rat hepatocytes sensitized by inhibition of RNA synthesis. Hepatology 30, 215–222.10.1002/hep.510300146Search in Google Scholar

Karakashian, A.A., Giltiay, N.V., Smith, G.M., and Nikolova-Karakashian, M.N. (2004). Expression of neutral sphingomyelinase-2 (NSMase-2) in primary rat hepatocytes modulates IL-β-induced JNK activation. FASEB J. 18, 968–970.10.1096/fj.03-0875fjeSearch in Google Scholar

Khashab, M., Tector, A.J., and Kwo, P.Y. (2007). Epidemiology of acute liver failure. Curr. Gastroenterol. Rep. 9, 66–73.10.1007/s11894-008-0023-xSearch in Google Scholar

Kim, M.Y., Linardic, C., Obeid, L., and Hannun, Y. (1991). Identification of sphingomyelin turnover as an effector mechanism for the action of tumor necrosis factor α and γ-interferon. Specific role in cell differentiation. J. Biol. Chem. 266, 484–489.10.1016/S0021-9258(18)52461-3Search in Google Scholar

Kolesnick, R. (1994). Signal transduction through the sphingomyelin pathway. Mol. Chem. Neuropathol. 21, 287–297.10.1007/BF02815356Search in Google Scholar

Kolesnick, R.N. and Clegg, S. (1988). 1,2-Diacylglycerols, but not phorbol esters, activate a potential inhibitory pathway for protein kinase C in GH3 pituitary cells. Evidence for involvement of a sphingomyelinase. J. Biol. Chem. 263, 6534–6537.10.1016/S0021-9258(18)68674-0Search in Google Scholar

Kuboki, S., Okaya, T., Schuster, R., Blanchard, J., Denenberg, A., Wong, H.R., and Lentsch, A.B. (2007). Hepatocyte NF-κB activation is hepatoprotective during ischemia-reperfusion injury and is augmented by ischemic hypothermia. Am. J. Physiol. Gastrointest. Liver Physiol. 292, G201–G207.10.1152/ajpgi.00186.2006Search in Google Scholar PubMed

Kuboki, S., Sakai, N., Tschop, J., Edwards, M.J., Lentsch, A.B., and Caldwell, C.C. (2009). Distinct contributions of CD4+ T cell subsets in hepatic ischemia/reperfusion injury. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G1054–1059.10.1152/ajpgi.90464.2008Search in Google Scholar PubMed PubMed Central

Lahiri, S. and Futerman, A.H. (2007). The metabolism and function of sphingolipids and glycosphingolipids. Cell. Mol. Life Sci. 64, 2270–2284.10.1007/s00018-007-7076-0Search in Google Scholar PubMed

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., et al. (2007). Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide. Nat. Med. 13, 164–170.10.1038/nm1539Search in Google Scholar PubMed

Larson, A.M., Polson, J., Fontana, R.J., Davern, T.J., Lalani, E., Hynan, L.S., Reisch, J.S., Schiodt, F.V., Ostapowicz, G., Shakil, A.O., et al. (2005). Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology 42, 1364–1372.10.1002/hep.20948Search in Google Scholar PubMed

Le Stunff, H., Milstien, S., and Spiegel, S. (2004). Generation and metabolism of bioactive sphingosine-1-phosphate. J. Cell. Biochem. 92, 882–899.10.1002/jcb.20097Search in Google Scholar PubMed

Lentsch, A.B., Yoshidome, H., Cheadle, W.G., Miller, F.N., and Edwards, M.J. (1998a). Chemokine involvement in hepatic ischemia/reperfusion injury in mice: roles for macrophage inflammatory protein-2 and KC. Hepatology 27, 1172–1177.10.1002/hep.510270441Search in Google Scholar

Lentsch, A.B., Yoshidome, H., Cheadle, W.G., Miller, F.N., and Edwards, M.J. (1998b). Chemokine involvement in hepatic ischemia/reperfusion injury in mice: roles for macrophage inflammatory protein-2 and Kupffer cells. Hepatology 27, 507–512.10.1002/hep.510270226Search in Google Scholar PubMed

Lentsch, A.B., Yoshidome, H., Kato, A., Warner, R.L., Cheadle, W.G., Ward, P.A., and Edwards, M.J. (1999). Requirement for interleukin-12 in the pathogenesis of warm hepatic ischemia/reperfusion injury in mice. Hepatology 30, 1448–1453.10.1002/hep.510300615Search in Google Scholar PubMed

Levade, T. and Jaffrezou, J.P. (1999). Signalling sphingomyelinases: which, where, how and why? Biochim. Biophys. Acta 1438, 1–17.Search in Google Scholar

Levy, M. and Futerman, A.H. (2010). Mammalian ceramide synthases. IUBMB Life 62, 347–356.10.1002/iub.319Search in Google Scholar PubMed PubMed Central

Li, C., Jiang, X., Yang, L., Liu, X., Yue, S., and Li, L. (2009a). Involvement of sphingosine 1-phosphate (SIP)/S1P3 signaling in cholestasis-induced liver fibrosis. Am. J. Pathol. 175, 1464–1472.10.2353/ajpath.2009.090037Search in Google Scholar PubMed PubMed Central

Li, C., Kong, Y., Wang, H., Wang, S., Yu, H., Liu, X., Yang, L., Jiang, X., Li, L., and Li, L. (2009b). Homing of bone marrow mesenchymal stem cells mediated by sphingosine 1-phosphate contributes to liver fibrosis. J. Hepatol. 50, 1174–1183.10.1016/j.jhep.2009.01.028Search in Google Scholar PubMed

Li, C., Zheng, S., You, H., Liu, X., Lin, M., Yang, L., and Li, L. (2011). Sphingosine 1-phosphate (S1P)/S1P receptors are involved in human liver fibrosis by action on hepatic myofibroblasts motility. J. Hepatol. 54, 1205–1213.10.1016/j.jhep.2010.08.028Search in Google Scholar PubMed

Limaye, V., Vadas, M.A., Pitson, S.M., and Gamble, J.R. (2009). The effects of markedly raised intracellular sphingosine kinase-1 activity in endothelial cells. Cell. Mol. Biol. Lett. 14, 411–423.10.2478/s11658-009-0008-2Search in Google Scholar PubMed PubMed Central

Liu, H., Sugiura, M., Nava, V.E., Edsall, L.C., Kono, K., Poulton, S., Milstien, S., Kohama, T., and Spiegel, S. (2000). Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. J. Biol. Chem. 275, 19513–19520.10.1074/jbc.M002759200Search in Google Scholar

Liu, Q., Rehman, H., Shi, Y., Krishnasamy, Y., Lemasters, J.J., Smith, C.D., and Zhong, Z. (2012). Inhibition of sphingosine kinase-2 suppresses inflammation and attenuates graft injury after liver transplantation in rats. PLoS One 7, e41834.10.1371/journal.pone.0041834Search in Google Scholar

Llacuna, L., Mari, M., Garcia-Ruiz, C., Fernandez-Checa, J.C., and Morales, A. (2006). Critical role of acidic sphingomyelinase in murine hepatic ischemia-reperfusion injury. Hepatology 44, 561–572.10.1002/hep.21285Search in Google Scholar

Luedde, T. and Trautwein, C. (2006). Intracellular survival pathways in the liver. Liver Int. 26, 1163–1174.10.1111/j.1478-3231.2006.01366.xSearch in Google Scholar

Maggio, B., Fanani, M.L., Rosetti, C.M., and Wilke, N. (2006). Biophysics of sphingolipids II. Glycosphingolipids: an assortment of multiple structural information transducers at the membrane surface. Biochim. Biophys. Acta 1758, 1922–1944.10.1016/j.bbamem.2006.04.020Search in Google Scholar

Mari, M., Colell, A., Morales, A., Paneda, C., Varela-Nieto, I., Garcia-Ruiz, C., and Fernandez-Checa, J.C. (2004). Acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor-induced lethal hepatitis. J. Clin. Invest. 113, 895–904.10.1172/JCI200419852Search in Google Scholar

McGill, M.R., Sharpe, M.R., Williams, C.D., Taha, M., Curry, S.C., and Jaeschke, H. (2012). The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. J. Clin. Invest. 122, 1574–1583.10.1172/JCI59755Search in Google Scholar

Meyer, S.G. and de Groot, H. (2003). Cycloserine and threo-dihydrosphingosine inhibit TNF-alpha-induced cytotoxicity: evidence for the importance of de novo ceramide synthesis in TNF-α signaling. Biochim. Biophys. Acta 1643, 1–4.10.1016/j.bbamcr.2003.10.002Search in Google Scholar

Meyer zu Heringdorf, D., Lass, H., Kuchar, I., Lipinski, M., Alemany, R., Rumenapp, U., and Jakobs, K.H. (2001). Stimulation of intracellular sphingosine-1-phosphate production by G-protein-coupled sphingosine-1-phosphate receptors. Eur. J. Pharmacol. 414, 145–154.10.1016/S0014-2999(01)00789-0Search in Google Scholar

Michalopoulos, G., Houck, K.A., Dolan, M.L., and Leutteke, N.C. (1984). Control of hepatocyte replication by two serum factors. Cancer Res. 44, 4414–4419.Search in Google Scholar

Michalopoulos, G.K. (2007). Liver regeneration. J. Cell. Physiol. 213, 286–300.10.1002/jcp.21172Search in Google Scholar PubMed PubMed Central

Moles, A., Tarrats, N., Morales, A., Dominguez, M., Bataller, R., Caballeria, J., Garcia-Ruiz, C., Fernandez-Checa, J.C., and Mari, M. (2010). Acidic sphingomyelinase controls hepatic stellate cell activation and in vivo liver fibrogenesis. Am. J. Pathol. 177, 1214–1224.10.2353/ajpath.2010.091257Search in Google Scholar

Mullen, T.D., Hannun, Y.A., Obeid, L.M., (2012). Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem. J. 441, 789–802.10.1042/BJ20111626Search in Google Scholar

Nakamura, T., Nawa, K., and Ichihara, A. (1984). Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats. Biochem. Biophys. Res. Commun. 122, 1450–1459.10.1016/0006-291X(84)91253-1Search in Google Scholar

Nebigil, C.G. (1997). Suppression of phospholipase C β, γ, and δ families alters cell growth and phosphatidylinositol 4,5-bisphosphate levels. Biochemistry 36, 15949–15958.10.1021/bi971721mSearch in Google Scholar PubMed

Nikolova-Karakashian, M., Morgan, E.T., Alexander, C., Liotta, D.C., and Merrill, A.H., Jr. (1997). Bimodal regulation of ceramidase by interleukin-1β. Implications for the regulation of cytochrome p450 2C11. J. Biol. Chem. 272, 18718–18724.10.1074/jbc.272.30.18718Search in Google Scholar PubMed

Nixon, G.F. (2009). Sphingolipids in inflammation: pathological implications and potential therapeutic targets. Br. J. Pharmacol. 158, 982–993.10.1111/j.1476-5381.2009.00281.xSearch in Google Scholar PubMed PubMed Central

Novgorodov, S.A. and Gudz, T.I. (2009). Ceramide and mitochondria in ischemia/reperfusion. J. Cardiovasc. Pharmacol. 53, 198–208.10.1097/FJC.0b013e31819b52d5Search in Google Scholar PubMed PubMed Central

Obinata, H. and Hla, T. (2012). Sphingosine 1-phosphate in coagulation and inflammation. Semin. Immunopathol. 34, 73–91.10.1007/s00281-011-0287-3Search in Google Scholar PubMed PubMed Central

Ogretmen, B. and Hannun, Y.A. (2004). Biologically active sphingolipids in cancer pathogenesis and treatment. Nat. Rev. Cancer 4, 604–616.10.1038/nrc1411Search in Google Scholar PubMed

Olivera, A., Kohama, T., Edsall, L., Nava, V., Cuvillier, O., Poulton, S., and Spiegel, S. (1999). Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival. J. Cell. Biol. 147, 545–558.10.1083/jcb.147.3.545Search in Google Scholar PubMed PubMed Central

Osawa, Y., Banno, Y., Nagaki, M., Brenner, D.A., Naiki, T., Nozawa, Y., Nakashima, S., and Moriwaki, H. (2001). TNF-α-induced sphingosine 1-phosphate inhibits apoptosis through a phosphatidylinositol 3-kinase/Akt pathway in human hepatocytes. J. Immunol. 167, 173–180.10.4049/jimmunol.167.1.173Search in Google Scholar PubMed

Osawa, Y., Uchinami, H., Bielawski, J., Schwabe, R.F., Hannun, Y.A., and Brenner, D.A. (2005). Roles for C16-ceramide and sphingosine 1-phosphate in regulating hepatocyte apoptosis in response to tumor necrosis factor-α. J. Biol. Chem. 280, 27879–27887.10.1074/jbc.M503002200Search in Google Scholar PubMed

Ostapowicz, G., Fontana, R.J., Schiodt, F.V., Larson, A., Davern, T.J., Han, S.H., McCashland, T.M., Shakil, A.O., Hay, J.E., Hynan, L., et al. (2002). Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann. Intern. Med. 137, 947–954.10.7326/0003-4819-137-12-200212170-00007Search in Google Scholar PubMed

Park, S.W., Kim, M., Chen, S.W., Brown, K.M., D’Agati, V.D., and Lee, H.T. (2010). Sphinganine-1-phosphate protects kidney and liver after hepatic ischemia and reperfusion in mice through S1P1 receptor activation. Lab. Invest. 90, 1209–1224.10.1038/labinvest.2010.102Search in Google Scholar PubMed PubMed Central

Park, J.W., Park, W.J., Kuperman, Y., Boura-Halfon, S., Pewzner-Jung, Y., and Futerman, A.H. (2013a). Ablation of very long acyl chain sphingolipids causes hepatic insulin resistance in mice due to altered detergent-resistant membranes. Hepatology 57, 525–532.10.1002/hep.26015Search in Google Scholar PubMed

Park, W.J., Park, J.W., Erez-Roman, R., Kogot-Levin, A., Bame, J.R., Tirosh, B., Saada, A., Merrill, A.H., Jr., Pewzner-Jung, Y., and Futerman, A.H. (2013b). Protection of a ceramide synthase 2 null mouse from drug-induced liver injury: role of gap junction dysfunction and connexin 32 mislocalization. J. Biol. Chem. 288, 30904–30916.10.1074/jbc.M112.448852Search in Google Scholar PubMed PubMed Central

Park, J.W., Park, W.J., and Futerman, A.H. (2014). Ceramide synthases as potential targets for therapeutic intervention in human diseases. Biochim. Biophys. Acta 1841, 671–681.10.1016/j.bbalip.2013.08.019Search in Google Scholar PubMed

Pettus, B.J., Kroesen, B.J., Szulc, Z.M., Bielawska, A., Bielawski, J., Hannun, Y.A., and Busman, M. (2004). Quantitative measurement of different ceramide species from crude cellular extracts by normal-phase high-performance liquid chromatography coupled to atmospheric pressure ionization mass spectrometry. Rapid Commun. Mass Spectrom. 18, 577–583.10.1002/rcm.1373Search in Google Scholar PubMed

Pewzner-Jung, Y., Brenner, O., Braun, S., Laviad, E.L., Ben-Dor, S., Feldmesser, E., Horn-Saban, S., Amann-Zalcenstein, D., Raanan, C., Berkutzki, T., et al. (2010). A critical role for ceramide synthase 2 in liver homeostasis: II. insights into molecular changes leading to hepatopathy. J. Biol. Chem. 285, 10911–10923.10.1074/jbc.M109.077610Search in Google Scholar PubMed PubMed Central

Polson, J. and Lee, W.M. (2007). Etiologies of acute liver failure: location, location, location! Liver Transpl. 13, 1362–1363.Search in Google Scholar

Quillin, R.C., 3rd, Wilson, G.C., Nojima, H., Freeman, C.M., Wang, J., Schuster, R.M., Blanchard, J.A., Edwards, M.J., Gandhi, C.R., Gulbins, E., et al. (2015). Inhibition of acidic sphingomyelinase reduces established hepatic fibrosis in mice. Hepatol. Res. 45, 305–314.10.1111/hepr.12352Search in Google Scholar PubMed PubMed Central

Raichur, S., Wang, S.T., Chan, P.W., Li, Y., Ching, J., Chaurasia, B., Dogra, S., Ohman, M.K., Takeda, K., Sugii, S., et al. (2014). CerS2 haploinsufficiency inhibits beta-oxidation and confers susceptibility to diet-induced steatohepatitis and insulin resistance. Cell Metab. 20, 687–695.10.1016/j.cmet.2014.09.015Search in Google Scholar

Refsnes, M., Dajani, O.F., Sandnes, D., Thoresen, G.H., Rottingen, J.A., Iversen, J.G., and Christoffersen, T. (1995). On the mechanisms of the growth-promoting effect of prostaglandins in hepatocytes: the relationship between stimulation of DNA synthesis and signaling mediated by adenylyl cyclase and phosphoinositide-specific phospholipase C. J. Cell Physiol. 164, 465–473.10.1002/jcp.1041640304Search in Google Scholar

Rutkute, K., Karakashian, A.A., Giltiay, N.V., Dobierzewska, A., and Nikolova-Karakashian, M.N. (2007). Aging in rat causes hepatic hyperresposiveness to interleukin-1β which is mediated by neutral sphingomyelinase-2. Hepatology 46, 1166–1176.10.1002/hep.21777Search in Google Scholar

Shi, Y., Rehman, H., Ramshesh, V.K., Schwartz, J., Liu, Q., Krishnasamy, Y., Zhang, X., Lemasters, J.J., Smith, C.D., and Zhong, Z. (2012). Sphingosine kinase-2 inhibition improves mitochondrial function and survival after hepatic ischemia-reperfusion. J. Hepatol. 56, 137–145.10.1016/j.jhep.2011.05.025Search in Google Scholar

Snider, A.J., Orr Gandy, K.A., and Obeid, L.M. (2010). Sphingosine kinase: role in regulation of bioactive sphingolipid mediators in inflammation. Biochimie 92, 707–715.10.1016/j.biochi.2010.02.008Search in Google Scholar

Spiegel, S. and Milstien, S. (2000a). Functions of a new family of sphingosine-1-phosphate receptors. Biochim. Biophys. Acta 1484, 107–116.10.1016/S1388-1981(00)00010-XSearch in Google Scholar

Spiegel, S. and Milstien, S. (2000b). Sphingosine-1-phosphate: signaling inside and out. FEBS Lett. 476, 55–57.10.1016/S0014-5793(00)01670-7Search in Google Scholar

Spiegel, S. and Milstien, S. (2003). Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat. Rev. Mol. Cell. Biol. 4, 397–407.10.1038/nrm1103Search in Google Scholar PubMed

Suzuki, S. and Toledo-Pereyra, L.H. (1994). Interleukin 1 and tumor necrosis factor production as the initial stimulants of liver ischemia and reperfusion injury. J. Surg. Res. 57, 253–258.10.1006/jsre.1994.1140Search in Google Scholar PubMed

Tagaram, H.R., Divittore, N.A., Barth, B.M., Kaiser, J.M., Avella, D., Kimchi, E.T., Jiang, Y., Isom, H.C., Kester, M., and Staveley-O’Carroll, K.F. (2011). Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma. Gut 60, 695–701.10.1136/gut.2010.216671Search in Google Scholar PubMed

Tsuchihashi, S., Ke, B., Kaldas, F., Flynn, E., Busuttil, R.W., Briscoe, D.M., and Kupiec-Weglinski, J.W. (2006). Vascular endothelial growth factor antagonist modulates leukocyte trafficking and protects mouse livers against ischemia/reperfusion injury. Am. J. Pathol. 168, 695–705.10.2353/ajpath.2006.050759Search in Google Scholar

Tsung, A., Sahai, R., Tanaka, H., Nakao, A., Fink, M.P., Lotze, M.T., Yang, H., Li, J., Tracey, K.J., Geller, D.A., et al. (2005). The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. J. Exp. Med. 201, 1135–1143.10.1084/jem.20042614Search in Google Scholar

Turnbull, K.J., Brown, B.L., and Dobson, P.R. (1999). Caspase-3-like activity is necessary but not sufficient for daunorubicin-induced apoptosis in Jurkat human lymphoblastic leukemia cells. Leukemia 13, 1056–1061.10.1038/sj.leu.2401438Search in Google Scholar

Uchida, Y., Nardo, A.D., Collins, V., Elias, P.M., and Holleran, W.M. (2003). De novo ceramide synthesis participates in the ultraviolet B irradiation-induced apoptosis in undifferentiated cultured human keratinocytes. J. Invest. Dermatol. 120, 662–669.10.1046/j.1523-1747.2003.12098.xSearch in Google Scholar

Uehara, T., Bennett, B., Sakata, S.T., Satoh, Y., Bilter, G.K., Westwick, J.K., and Brenner, D.A. (2005). JNK mediates hepatic ischemia reperfusion injury. J. Hepatol. 42, 850–859.10.1016/j.jhep.2005.01.030Search in Google Scholar

Vessey, D.A., Li, L., Jin, Z.Q., Kelley, M., Honbo, N., Zhang, J., and Karliner, J.S. (2011). A sphingosine kinase form 2 knockout sensitizes mouse myocardium to ischemia/reoxygenation injury and diminishes responsiveness to ischemic preconditioning. Oxidat. Med. Cell. Longevity 2011, 961059.10.1155/2011/961059Search in Google Scholar

Wanner, G.A., Ertel, W., Muller, P., Hofer, Y., Leiderer, R., Menger, M.D., and Messmer, K. (1996). Liver ischemia and reperfusion induces a systemic inflammatory response through Kupffer cell activation. Shock 5, 34–40.10.1097/00024382-199601000-00008Search in Google Scholar

Watanabe, A., Nakashima, S., Adachi, T., Saji, S., and Nozawa, Y. (2000). Changes in the expression of lipid-mediated signal-transducing enzymes in the rat liver after partial hepatectomy. Surg. Today 30, 622–630.10.1007/s005950070102Search in Google Scholar

Webber, E.M., Bruix, J., Pierce, R.H., and Fausto, N. (1998). Tumor necrosis factor primes hepatocytes for DNA replication in the rat. Hepatology 28, 1226–1234.10.1002/hep.510280509Search in Google Scholar

Wiegmann, K., Schutze, S., Machleidt, T., Witte, D., and Kronke, M. (1994). Functional dichotomy of neutral and acidic sphingomyelinases in tumor necrosis factor signaling. Cell 78, 1005–1015.10.1016/0092-8674(94)90275-5Search in Google Scholar

Xiong, Y., Lee, H.J., Mariko, B., Lu, Y.C., Dannenberg, A.J., Haka, A.S., Maxfield, F.R., Camerer, E., Proia, R.L., and Hla, T. (2013). Sphingosine kinases are not required for inflammatory responses in macrophages. J. Biol. Chem. 288, 32563–32573.10.1074/jbc.M113.483750Search in Google Scholar PubMed PubMed Central

Yang, L., Chang, N., Liu, X., Han, Z., Zhu, T., Li, C., Yang, L., and Li, L. (2012). Bone marrow-derived mesenchymal stem cells differentiate to hepatic myofibroblasts by transforming growth factor-β1 via sphingosine kinase/sphingosine 1-phosphate (S1P)/S1P receptor axis. Am. J. Pathol. 181, 85–97.10.1016/j.ajpath.2012.03.014Search in Google Scholar PubMed

Yu, J., Novgorodov, S.A., Chudakova, D., Zhu, H., Bielawska, A., Bielawski, J., Obeid, L.M., Kindy, M.S., and Gudz, T.I. (2007). JNK3 signaling pathway activates ceramide synthase leading to mitochondrial dysfunction. J. Biol. Chem. 282, 25940–25949.10.1074/jbc.M701812200Search in Google Scholar PubMed

Zabielski, P., Baranowski, M., Zendzian-Piotrowska, M., Blachnio, A., and Gorski, J. (2007). Partial hepatectomy activates production of the pro-mitotic intermediates of the sphingomyelin signal transduction pathway in the rat liver. Prostaglandins Other Lipid Mediat. 83, 277–284.10.1016/j.prostaglandins.2007.02.001Search in Google Scholar PubMed

Zimmermann, A. (2004). Regulation of liver regeneration. Nephrol. Dial. Transplant. 19 (Suppl. 4), iv6–10.10.1093/ndt/gfh1034Search in Google Scholar PubMed

Zwacka, R.M., Zhang, Y., Halldorson, J., Schlossberg, H., Dudus, L., and Engelhardt, J.F. (1997). CD4+ T-lymphocytes mediate ischemia/reperfusion-induced inflammatory responses in mouse liver. J. Clin. Invest. 100, 279–289.10.1172/JCI119533Search in Google Scholar PubMed PubMed Central

Received: 2014-12-4
Accepted: 2015-3-9
Published Online: 2015-3-12
Published in Print: 2015-6-1

©2015 by De Gruyter

Downloaded on 31.5.2024 from https://www.degruyter.com/document/doi/10.1515/hsz-2014-0296/html
Scroll to top button