Activation of LXRs prevents bile acid toxicity and cholestasis in female mice

Hepatology

Volumn 45, Issue 2, 2007, Pages 422-432

  Uppal, Hirdesh ^a,b   Saini, Simrat P S ^a   Moschetta, Antonio ^c   Mu, Ying ^a   Zhou, Jie ^a   Gong, Haibiao ^a   Zhai, Yonggong ^a   Ren, Songrong ^a   Michalopoulos, George K ^b   Mangelsdorf, David J ^c   Xie, Wen ^a,b  

^a UNIVERSITY OF PITTSBURGH   (United States)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BILE ACID; LIGAND; LITHOCHOLIC ACID; LIVER X RECEPTOR ALPHA; LIVER X RECEPTOR BETA; OXYGENASE; OXYSTEROL; OXYSTEROL 7ALPHA HYDROXYLASE; SULFOTRANSFERASE; SULFOTRANSFERASE 2A; SULFOTRANSFERASE 2A9; TO 1317; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BILE ACID METABOLISM; BILE DUCT LIGATION; CHOLESTASIS; CHOLESTEROL METABOLISM; CONTROLLED STUDY; FEMALE; HOMEOSTASIS; KNOCKOUT MOUSE; LIVER TOXICITY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRANSGENIC MOUSE;

ANIMALS; BILE ACIDS AND SALTS; CHOLESTASIS; CHOLESTEROL; CYTOCHROME P-450 ENZYME SYSTEM; DNA-BINDING PROTEINS; FEMALE; HOMEOSTASIS; LITHOCHOLIC ACID; MICE; MICE, TRANSGENIC; RECEPTORS, CYTOPLASMIC AND NUCLEAR; SEX CHARACTERISTICS; STEROID HYDROXYLASES; SULFOTRANSFERASES;

EID: 33847699765     PISSN: 02709139     EISSN: None     Source Type: Journal    
DOI: 10.1002/hep.21494     Document Type: Article

References (58)

1. Repa JJ, Mangelsdorf DJ. The liver X receptor gene team: potential new players in atherosclerosis. Nat Med 2002;8:1243-1248.
2. Tontonoz P, Mangelsdorf DJ. Liver X receptor signaling pathways in cardiovascular disease. Mol Endocrinol 2003;17:985-993.
3. Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L, et al. Role of LXRs in control of lipogenesis. Genes Dev 2000;14:2831-2838.
4. Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ. Nuclear receptors and lipid physiology: opening the X-files. Science 2001;294:1866-1870.
5. Peet DJ, Turley SD, Ma W, Janowski BA, Lobaccaro JM, Hammer RE, et al. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell 1998;93:693-704.
6. Chiang JY, Kimmel R, Stroup D. Regulation of cholesterol 7alpha-hydroxylase gene (CYP7A1) transcription by the liver orphan receptor (LXRalpha). Gene 2001;262:257-265.
7. Goodwin B, Watson MA, Kim H, Miao J, Kemper JK, Kliewer SA. Differential regulation of rat and human CYP7A1 by the nuclear oxysterol receptor liver X receptor-alpha. Mol Endocrinol 2003;17:386-394.
8. Trauner M, Boyer JL. Cholestatic syndromes. Curr Opin Gastroenterol 2004;20:220-230.
9. Liu Y, Binz J, Numerick MJ, Dennis S, Luo G, Desai B, et al. Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis. J Clin Invest 2003;112:1678-1687.
10. Saini SP, Sonoda J, Xu L, Toma D, Uppal H, Mu Y, et al. A novel constitutive androstane receptor-mediated and CYP3A-independent pathway of bile acid detoxification. Mol Pharmacol 2004;65:292-300.
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. Uppal H, Toma D, Saini SP, Ren S, Jones TJ, Xie W. Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice. HEPATOLOGY 2005;41:168-176.
13. Wang L, Han Y, Kim CS, Lee YK, Moore DD. Resistance of SHP-null mice to bile acid-induced liver damage. J Biol Chem 2003;278:44475-44481.
14. 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.
15. Zhang J, Huang W, Qatanani M, Evans RM, Moore DD. The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity. J Biol Chem 2004;279:49517-49522.
16. Boyer JL. Nuclear receptor ligands: rational and effective therapy for chronic cholestatic liver disease? Gastroenterology 2005;129:735-740.
17. Chiang JY. Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms. J Hepatol 2004;40:539-551.
18. Karpen SJ. Exercising the nuclear option to treat cholestasis: CAR and PXR ligands. HEPATOLOGY 2005;42:266-269.
19. Repa JJ, Turley SD, Lobaccaro JA, Medina J, Li L, Lustig K, et al. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 2000;289:1524-1529.
20. Barish GD, Evans RM. A nuclear strike against Listeria - the evolving life of LXR. Cell 2004;119:149-151.
21. Joseph SB, Bradley MN, Castrillo A, Bruhn KW, Mak PA, Pei L, et al. LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 2004;119:299-309.
22. Joseph SB, Castrillo A, Laffitte BA, Mangelsdorf DJ, Tontonoz P. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat Med 2003;9:213-219.
23. Kim JB, Spiegelman BM. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev 1996;10:1096-1107.
24. Lehrke M, Lebherz C, Millington SC, Guan HP, Millar J, Rader DJ, et al. Diet-dependent cardiovascular lipid metabolism controlled by hepatic LXRalpha. Cell Metab 2005;1:297-308.
25. Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, et al. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev 2000;14:2819-2830.
26. Shimano H, Yahagi N, Amemiya-Kudo M, Hasty AH, Osuga J, Tamura Y, et al. Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes. J Biol Chem 1999;274:35832-35839.
27. Gong H, Singh SV, Singh SP, Mu Y, Lee JH, Saini SP, et al. Orphan nuclear receptor PXR sensitizes oxidative stress responses in transgenic mice and cancerous cells. Mol Endocrinol 2006;20:279-290.
28. Stedman CA, Liddle C, Coulter SA, Sonoda J, Alvarez JG, Moore DD, et al. Nuclear receptors constitutive androstane receptor and pregnane X receptor ameliorate cholestatic liver injury. Proc Natl Acad Sci U S A 2005;102:2063-2068.
29. Mu Y, Stephenson CR, Kendall C, Saini SP, Toma D, Ren S, et al. A pregnane X receptor agonist with unique species-dependent stereoselectivity and its implications in drug development. Mol Pharmacol 2005;68:403-413.
30. Xie W, Barwick JL, Simon CM, Pierce AM, Safe S, Blumberg B, et al. Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes Dev 2000;14:3014-3023.
31. Zhou J, Zhai Y, Mu Y, Gong H, Uppal H, Toma D, et al. A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J Biol Chem 2006;281:15013-15020.
32. Kullak-Ublick GA, Stieger B, Hagenbuch B, Meier PJ. Hepatic transport of bile salts. Semin Liver Dis 2000;20:273-292.
33. Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 2003;83:633-671.
34. Xie W, Uppal H, Saini SP, Mu Y, Little JM, Radominska-Pandya A, et al. Orphan nuclear receptor-mediated xenobiotic regulation in drug metabolism. Drug Discov Today 2004;9:442-449.
35. Assem M, Schuetz EG, Leggas M, Sun D, Yasuda K, Reid G, et al. Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice. J Biol Chem 2004;279:22250-22257.
36. Mennone A, Soroka CJ, Cai SY, Harry K, Adachi M, Hagey L, et al. Mrp4-/- mice have an impaired cytoprotective response in obstructive cholestasis. Hepatology 2006;43:1013-1021.
37. Sonoda J, Xie W, Rosenfeld JM, Barwick JL, Guzelian PS, Evans RM. Regulation of a xenobiotic sulfonation cascade by nuclear pregnane X receptor (PXR). Proc Natl Acad Sci U S A 2002;99:13801-13806.
38. Ballatori N, Christian WV, Lee JY, Dawson PA, Soroka CJ, Boyer JL, et al. OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia. HEPATOLOGY 2005;42:1270-1279.
39. Dawson PA, Hubbert M, Haywood J, Craddock AL, Zerangue N, Christian WV, Ballatori N. The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is an ileal basolateral bile acid transporter. J Biol Chem 2005;280:6960-6968.
40. Song CS, Echchgadda I, Baek BS, Ahn SC, Oh T, Roy AK, et al. Dehydroepiandrosterone sulfotransferase gene induction by bile acid activated farnesoid X receptor. J Biol Chem 2001;276:42549-42556.
41. Omary MB, Ku NO, Toivola DM. Keratins: guardians of the liver. Hepatology 2002;35:251-257.
42. Chu XY, Huskey SE, Braun MP, Sarkadi B, Evans DC, Evers R. Transport of ethinylestradiol glucuronide and ethinylestradiol sulfate by the multidrug resistance proteins MRP1, MRP2, and MRP3. J Pharmacol Exp Ther 2004;309:156-164.
43. Crocenzi FA, Mottino AD, Cao J, Veggi LM, Pozzi EJ, Vore M, et al. Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in rats. Am J Physiol Gastrointest Liver Physiol 2003;285:G449-G459.
44. Mottino AD, Crocenzi FA, Pozzi EJ, Veggi LM, Roma MG, Vore M. Role of microtubules in estradiol-17beta-D-glucuronide-induced alteration of canalicular Mrp2 localization and activity. Am J Physiol Gastrointest Liver Physiol 2005;288:G327-G336.
45. Mottino AD, Veggi LM, Wood M, Roman JM, Vore M. Biliary secretion of glutathione in estradiol 17beta-glucuronide-induced cholestasis. J Pharmacol Exp Ther 2003;307:306-313.
46. Kaplan MM, Gershwin ME. Primary biliary cirrhosis. N Engl J Med 2005;353:1261-1273.
47. Shenoy SD, Spencer TA, Mercer-Haines NA, Alipour M, Gargano MD, Runge-Morris M, et al. CYP3A induction by liver x receptor ligands in primary cultured rat and mouse hepatocytes is mediated by the pregnane X receptor. Drug Metab Dispos 2004;32:66-71.
48. Maglich JM, Stoltz CM, Goodwin B, Hawkins-Brown D, Moore JT, Kliewer SA. Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol Pharmacol 2002;62:638-646.
49. Ueda A, Hamadeh HK, Webb HK, Yamamoto Y, Sueyoshi T, Afshari CA, et al. Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Mol Pharmacol 2002;61:1-6.
50. Makishima M, Lu TT, Xie W, Whitfield GK, Domoto H, Evans RM, et al. Vitamin D receptor as an intestinal bile acid sensor. Science 2002;296:1313-1316.
51. Rosenfeld JM, Vargas R Jr, Xie W, Evans RM. Genetic profiling defines the xenobiotic gene network controlled by the nuclear receptor pregnane X receptor. Mol Endocrinol 2003;17:1268-1282.
52. Xie W, Barwick JL, Downes M, Blumberg B, Simon CM, Nelson MC, et al. Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature 2000;406:435-439.
53. Xie W, Yeuh MF, Radominska-Pandya A, Saini SP, Negishi Y, Bottroff BS, et al. Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor. Proc Natl Acad Sci U S A 2003;100:4150-4155.
54. Saini SP, Mu Y, Gong H, Toma D, Uppal H, Ren S, et al. Dual role of orphan nuclear receptor pregnane X receptor in bilirubin detoxification in mice. HEPATOLOGY 2005;41:497-505.
55. Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Rang H, et al. Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell 2003;113:159-170.
56. Yang Q, Yamada A, Kimura S, Peters JM, Gonzalez FJ. Alterations in skin and stratified epithelia by constitutively activated PPARalpha. J Invest Dermatol 2006;126:374-385.
57. Norlin M, Chiang JY. Transcriptional regulation of human oxysterol 7alpha-hydroxylase by sterol response element binding protein. Biochem Biophys Res Commun 2004;316:158-164.
58. Li-Hawkins J, Lund EG, Turley SD, Russell DW. Disruption of the oxysterol 7alpha-hydroxylase gene in mice. J Biol Chem 2000;275:16536-16542.