• 1
    Carey MC, Small DM, Bliss CM. Lipid digestion and absorption. Annu Rev Physiol 1983; 45: 651-677.
  • 2
    Hernell O, Staggers JE, Carey MC. Physical-chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 2. Phase analysis and aggregation states of luminal lipids during duodenal fat digestion in healthy adult human beings. Biochemistry 1990; 29: 2041-2056.
  • 3
    Dionne S, Tuchweber B, Plaa GL, Yousef IM. Phase I and phase II metabolism of lithocholic acid in hepatic acinar zone 3 necrosis. Evaluation in rats by combined radiochromatography and gas-liquid chromatography-mass spectrometry. Biochem Pharmacol 1994; 48: 1187-1197.
  • 4
    Rodrigues CM, Steer CJ. Mitochondrial membrane perturbations in cholestasis. J Hepatol 2000; 32: 135-141.
  • 5
    Chen C, Gonzalez FJ, Idle JR. LC-MS-based metabolomics in drug metabolism. Drug Metab Rev 2007; 39: 581-597.
  • 6
    Marschall HU, Wagner M, Bodin K, Zollner G, Fickert P, Gumhold J, et al. Fxr(-/-) mice adapt to biliary obstruction by enhanced phase I detoxification and renal elimination of bile acids. J Lipid Res 2006; 47: 582-592.
  • 7
    Cho JY, Matsubara T, Kang DW, Ahn SH, Krausz KW, Idle JR, et al. Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge. J Lipid Res 2010; 51: 1063-1074.
  • 8
    Yousef IM, Perwaiz S, Lamireau T, Tuchweber B. Urinary bile acid profile in children with inborn errors of bile acid metabolism and chronic cholestasis; screening technique using electrospray tandem mass-spectrometry (ES/MS/MS). Med Sci Monit 2003; 9: MT21-31.
  • 9
    Festi D, Morselli Labate AM, Roda A, Bazzoli F, Frabboni R, Rucci P, et al. Diagnostic effectiveness of serum bile acids in liver diseases as evaluated by multivariate statistical methods. HEPATOLOGY 1983; 3-713. 707-713.
  • 10
    Hofmann AF. Detoxification of lithocholic acid, a toxic bile acid: relevance to drug hepatotoxicity. Drug Metab Rev 2004; 36: 703-722.
  • 11
    Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A 2001; 98: 3369-3374.
  • 12
    Xie W, Radominska-Pandya A, Shi Y, Simon CM, Nelson MC, Ong ES, et al. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci U S A 2001; 98: 3375-3380.
  • 13
    Kitada H, Miyata M, Nakamura T, Tozawa A, Honma W, Shimada M, et al. Protective role of hydroxysteroid sulfotransferase in lithocholic acid-induced liver toxicity. J Biol Chem 2003; 278: 17838-17844.
  • 14
    Uppal H, Saini SP, Moschetta A, Mu Y, Zhou J, Gong H, et al. Activation of LXRs prevents bile acid toxicity and cholestasis in female mice. HEPATOLOGY 2007; 45-432. 422-432.
  • 15
    Araya Z, Wikvall K. 6Alpha-hydroxylation of taurochenodeoxycholic acid and lithocholic acid by CYP3A4 in human liver microsomes. Biochim Biophys Acta 1999; 1438: 47-54.
  • 16
    Bodin K, Lindbom U, Diczfalusy U. Novel pathways of bile acid metabolism involving CYP3A4. Biochim Biophys Acta 2005; 1687: 84-93.
  • 17
    Miyata M, Watase H, Hori W, Shimada M, Nagata K, Gonzalez FJ, et al. Role for enhanced faecal excretion of bile acid in hydroxysteroid sulfotransferase-mediated protection against lithocholic acid-induced liver toxicity. Xenobiotica 2006; 36: 631-644.
  • 18
    Deo AK, Bandiera SM. 3-Ketocholanoic acid is the major in vitro human hepatic microsomal metabolite of lithocholic acid. Drug Metab Dispos 2009; 37: 1938-1947.
  • 19
    Miyata M, Nomoto M, Sotodate F, Mizuki T, Hori W, Nagayasu M, et al. Possible protective role of pregnenolone-16 alpha-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis. Eur J Pharmacol 2010; 636: 145-154.
  • 20
    Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 2000; 102: 731-744.
  • 21
    Chen C, Shah YM, Morimura K, Krausz KW, Miyazaki M, Richardson TA, et al. Metabolomics reveals that hepatic stearoyl-CoA desaturase 1 downregulation exacerbates inflammation and acute colitis. Cell Metab 2008; 7: 135-147.
  • 22
    Merrill AH Jr, Sullards MC, Allegood JC, Kelly S, Wang E. Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods 2005; 36: 207-224.
  • 23
    Seglen PO. Preparation of isolated rat liver cells. Methods Cell Biol 1976; 13: 29-83.
  • 24
    Farooqui AA, Taylor WA, Pendley CE, 2nd, Cox JW, Horrocks LA. Spectrophotometric determination of lipases, lysophospholipases, and phospholipases. J Lipid Res 1984; 25: 1555-1562.
  • 25
    Croset M, Brossard N, Polette A, Lagarde M. Characterization of plasma unsaturated lysophosphatidylcholines in human and rat. Biochem J 2000; 345 Pt 1: 61-67.
  • 26
    Wang A, Yang HC, Friedman P, Johnson CA, Dennis EA. A specific human lysophospholipase: cDNA cloning, tissue distribution and kinetic characterization. Biochim Biophys Acta 1999; 1437: 157-169.
  • 27
    Shindou H, Shimizu T. Acyl-CoA:lysophospholipid acyltransferases. J Biol Chem 2009; 284: 1-5.
  • 28
    Aoki J. Mechanisms of lysophosphatidic acid production. Semin Cell Dev Biol 2004; 15: 477-489.
  • 29
    Cummings R, Parinandi N, Wang L, Usatyuk P, Natarajan V. Phospholipase D/phosphatidic acid signal transduction: role and physiological significance in lung. Mol Cell Biochem 2002; 234-235:99-109. .
  • 30
    Exton JH. Regulation of phospholipase D. FEBS Lett 2002; 531: 58-61.
  • 31
    Kennedy EP, Weiss SB. The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem 1956; 222: 193-214.
  • 32
    Hannun YA. The sphingomyelin cycle and the second messenger function of ceramide. J Biol Chem 1994; 269: 3125-3128.
  • 33
    Sato M, Markiewicz M, Yamanaka M, Bielawska A, Mao C, Obeid LM, et al. Modulation of transforming growth factor-beta (TGF-beta) signaling by endogenous sphingolipid mediators. J Biol Chem 2003; 278: 9276-9282.
  • 34
    Neville NT, Parton J, Harwood JL, Jackson SK. The activities of monocyte lysophosphatidylcholine acyltransferase and coenzyme A-independent transacylase are changed by the inflammatory cytokines tumor necrosis factor alpha and interferon gamma. Biochim Biophys Acta 2005; 1733: 232-238.
  • 35
    Purohit V, Brenner DA. Mechanisms of alcohol-induced hepatic fibrosis: a summary of the Ron Thurman Symposium. HEPATOLOGY 2006; 43: 872-878.
  • 36
    Sekas G, Patton GM, Lincoln EC, Robins SJ. Origin of plasma lysophosphatidylcholine: evidence for direct hepatic secretion in the rat. J Lab Clin Med 1985; 105: 190-194.
  • 37
    Baisted DJ, Robinson BS, Vance DE. Albumin stimulates the release of lysophosphatidylcholine from cultured rat hepatocytes. Biochem J 1988; 253: 693-701.
  • 38
    Kume N, Cybulsky MI, Gimbrone MA Jr. Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest 1992; 90: 1138-1144.
  • 39
    Kohno M, Yokokawa K, Yasunari K, Minami M, Kano H, Hanehira T, et al. Induction by lysophosphatidylcholine, a major phospholipid component of atherogenic lipoproteins, of human coronary artery smooth muscle cell migration. Circulation 1998; 98: 353-359.
  • 40
    Liu-Wu Y, Hurt-Camejo E, Wiklund O. Lysophosphatidylcholine induces the production of IL-1beta by human monocytes. Atherosclerosis 1998; 137: 351-357.
  • 41
    Nishioka H, Horiuchi H, Arai H, Kita T. Lysophosphatidylcholine generates superoxide anions through activation of phosphatidylinositol 3-kinase in human neutrophils. FEBS Lett 1998; 441: 63-66.
  • 42
    Goldman R, Ferber E, Zort U. Reactive oxygen species are involved in the activation of cellular phospholipase A2. FEBS Lett 1992; 309: 190-192.
  • 43
    Yerushalmi B, Dahl R, Devereaux MW, Gumpricht E, Sokol RJ. Bile acid-induced rat hepatocyte apoptosis is inhibited by antioxidants and blockers of the mitochondrial permeability transition. HEPATOLOGY 2001; 33: 616-626.
  • 44
    Lands WE. Metabolism of glycerolipides; a comparison of lecithin and triglyceride synthesis. J Biol Chem 1958; 231: 883-888.
  • 45
    Liu B, Andrieu-Abadie N, Levade T, Zhang P, Obeid LM, Hannun YA. Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death. J Biol Chem 1998; 273: 11313-11320.
  • 46
    Wu BX, Clarke CJ, Hannun YA. Mammalian neutral sphingomyelinases: regulation and roles in cell signaling responses. Neuromolecular Med 2010; 12: 320-330.
  • 47
    Morales A, Lee H, Goni FM, Kolesnick R, Fernandez-Checa JC. Sphingolipids and cell death. Apoptosis 2007; 12: 923-939.
  • 48
    Reinehr R, Graf D, Haussinger D. Bile salt-induced hepatocyte apoptosis involves epidermal growth factor receptor-dependent CD95 tyrosine phosphorylation. Gastroenterology 2003; 125: 839-853.
  • 49
    Greim H, Trulzsch D, Czygan P, Rudick J, Hutterer F, Schaffner F, et al. Mechanism of cholestasis. 6. Bile acids in human livers with or without biliary obstruction. Gastroenterology 1972; 63: 846-850.
  • 50
    Koga H, Sakisaka S, Ohishi M, Sata M, Tanikawa K. Nuclear DNA fragmentation and expression of Bcl-2 in primary biliary cirrhosis. HEPATOLOGY 1997; 25: 1077-1084.
  • 51
    Lee JY, Leonhardt LG, Obeid LM. Cell-cycle-dependent changes in ceramide levels preceding retinoblastoma protein dephosphorylation in G2/M. Biochem J 1998; 334( Pt 2): 457-461.
  • 52
    Lister MD, Ruan ZS, Bittman R. Interaction of sphingomyelinase with sphingomyelin analogs modified at the C-1 and C-3 positions of the sphingosine backbone. Biochim Biophys Acta 1995; 1256: 25-30.
  • 53
    Qiao L, Yacoub A, Studer E, Gupta S, Pei XY, Grant S, et al. Inhibition of the MAPK and PI3K pathways enhances UDCA-induced apoptosis in primary rodent hepatocytes. HEPATOLOGY 2002; 35: 779-789.
  • 54
    Osawa Y, Seki E, Adachi M, Suetsugu A, Ito H, Moriwaki H, et al. Role of acid sphingomyelinase of Kupffer cells in cholestatic liver injury in mice. HEPATOLOGY 2010; 51: 237-245.
  • 55
    Canbay A, Feldstein AE, Higuchi H, Werneburg N, Grambihler A, Bronk SF, et al. Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression. HEPATOLOGY 2003; 38: 1188-1198.
  • 56
    Takiya S, Tagaya T, Takahashi K, Kawashima H, Kamiya M, Fukuzawa Y, et al. Role of transforming growth factor beta 1 on hepatic regeneration and apoptosis in liver diseases. J Clin Pathol 1995; 48: 1093-1097.