Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 302, Issue 9, 2012, Pages

  Weerachayaphorn, Jittima ^a,b   Mennone, Albert ^a   Soroka, Carol J ^a   Harry, Kathy ^a   Hagey, Lee R ^c   Kensler, Thomas W ^d   Boyer, James L ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b MAHIDOL UNIVERSITY   (Thailand)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

Biliary excretion; Glutathione; Nrf2 knockout mice; Obstructive cholestasis

Indexed keywords

BILE ACID; CHOLESTANETRIOL 26 MONOOXYGENASE; CHOLESTEROL 7ALPHA MONOOXYGENASE; CYTOCHROME P450 3A11; CYTOCHROME P450 CYP8B1 PROTEIN; GLUTATHIONE; ILEAL APICAL SODIUM DEPENDENT BILE ACID PROTEIN; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 2; MULTIDRUG RESISTANCE PROTEIN 3; MULTIDRUG RESISTANCE PROTEIN 4; PEPTIDES AND PROTEINS; PREGNANE X RECEPTOR; TRANSCRIPTION FACTOR NRF2; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BILE ACID HOMEOSTASIS; BILE ACID METABOLISM; BILE ACID SYNTHESIS; BILE DUCT LIGATION; BILE SECRETION; CHOLESTASIS; CONTROLLED STUDY; GENE DELETION; GENE EXPRESSION; GENETIC ANALYSIS; HOMEOSTASIS AND REGULATION; HYDROXYLATION; INTESTINE; LIVER; LIVER INJURY; MALE; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL;

ANIMALS; BILE ACIDS AND SALTS; CHOLESTASIS; HOMEOSTASIS; INTESTINES; LIVER; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NF-E2-RELATED FACTOR 2;

EID: 84860535208     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00263.2011     Document Type: Article

References (49)

1. Aboutwerat A, Pemberton PW, Smith A, Burrows PC, McMahon RF, Jain SK, Warnes TW. Oxidant stress is a significant feature of primary biliary cirrhosis. Biochim Biophys Acta 1637: 142-150, 2003.
2. Aleksunes LM, Slitt AL, Maher JM, Augustine LM, Goedken MJ, Chan JY, Cherrington NJ, Klaassen CD, Manautou JE. Induction of Mrp3 and Mrp4 transporters during acetaminophen hepatotoxicity is dependent on Nrf2. Toxicol Appl Pharmacol 226: 74-83, 2008.
3. Aleksunes LM, Slitt AL, Maher JM, Dieter MZ, Knight TR, Goedken M, Cherrington NJ, Chan JY, Klaassen CD, Manautou JE. Nuclear factor-E2-related factor 2 expression in liver is critical for induction of NAD(P)H:quinone oxidoreductase 1 during cholestasis. Cell Stress Chaperones 11: 356-363, 2006.
4. Ballatori N, Christian WV, Lee JY, Dawson PA, Soroka CJ, Boyer JL, Madejczyk MS, Li N. OSTα-OSTβ: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia. Hepatology 42: 1270-1279, 2005.
5. Ballatori N, Truong AT, Ma AK, Boyer JL. Determinants of glutathione efflux and biliary GSH/GSSG ratio in perfused rat liver. Am J Physiol Gastrointest Liver Physiol 256: G482-G490, 1989.
6. Chan K, Han XD, Kan YW. An important function of Nrf2 in combating oxidative stress: detoxification of acetaminophen. Proc Natl Acad Sci USA 98: 4611-4616, 2001.
7. Chiang JY. Bile acids: regulation of synthesis. J Lipid Res 50: 1955-1966, 2009.
8. Chowdhry S, Nazmy MH, Meakin PJ, Dinkova-Kostova AT, Walsh SV, Tsujita T, Dillon JF, Ashford ML, Hayes JD. Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis. Free Radic Biol Med 48: 357-371, 2010.
9. Del Castillo-Olivares A, Gil G. Suppression of sterol 12α-hydroxylase transcription by the short heterodimer partner: insights into the repression mechanism. Nucleic Acids Res 29: 4035-4042, 2001.
10. Enomoto A, Itoh K, Nagayoshi E, Haruta J, Kimura T, O'Connor T, Harada T, Yamamoto M. High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes. Toxicol Sci 59: 169-177, 2001.
11. Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol 45: 51-88, 2005.
12. Huang J, Tabbi-Anneni I, Gunda V, Wang L. Transcription factor Nrf2 regulates SHP and lipogenic gene expression in hepatic lipid metabolism. Am J Physiol Gastrointest Liver Physiol 299: G1211-G1221, 2010.
13. Inagaki T, Choi M, Moschetta A, Peng L, Cummins CL, McDonald JG, Luo G, Jones SA, Goodwin B, Richardson JA, Gerard RD, Repa JJ, Mangelsdorf DJ, Kliewer SA. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab 2: 217-225, 2005.
14. Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236: 313-322, 1997.
15. Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 47: 89-116, 2007.
16. Kim I, Ahn SH, Inagaki T, Choi M, Ito S, Guo GL, Kliewer SA, Gonzalez FJ. Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. J Lipid Res 48: 2664-2672, 2007.
17. Klaassen CD, Reisman SA. Nrf2 the rescue: effects of the antioxidative/ electrophilic response on the liver. Toxicol Appl Pharmacol 244: 57-65, 2010.
18. Kobayashi M, Yamamoto M. Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxid Redox Signal 7: 385-394, 2005.
19. Lamle J, Marhenke S, Borlak J, von Wasielewski R, Eriksson CJ, Geffers R, Manns MP, Yamamoto M, Vogel A. Nuclear factor-erythroid 2-related factor 2 prevents alcohol-induced fulminant liver injury. Gastroenterology 134: 1159-1168, 2008.
20. Li M, Wang W, Soroka CJ, Mennone A, Harry K, Weinman EJ, Boyer JL. NHERF-1 binds to Mrp2 and regulates hepatic Mrp2 expression and function. J Biol Chem 285: 19299-19307, 2010.
21. Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA, Auwerx J, Mangelsdorf DJ. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell 6: 507-515, 2000.
22. Maher JM, Dieter MZ, Aleksunes LM, Slitt AL, Guo G, Tanaka Y, Scheffer GL, Chan JY, Manautou JE, Chen Y, Dalton TP, Yamamoto M, Klaassen CD. Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway. Hepatology 46: 1597-1610, 2007.
23. -/- mice have an impaired cytoprotective response in obstructive cholestasis. Hepatology 43: 1013-1021, 2006.
24. Moi P, Chan K, Asunis I, Cao A, Kan YW. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the β-globin locus control region. Proc Natl Acad Sci USA 91: 9926-9930, 1994.
25. Moinova HR, Mulcahy RT. Up-regulation of the human γ-glutamylcysteine synthetase regulatory subunit gene involves binding of Nrf-2 to an electrophile responsive element. Biochem Biophys Res Commun 261: 661-668, 1999.
26. Okawa H, Motohashi H, Kobayashi A, Aburatani H, Kensler TW, Yamamoto M. Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity. Biochem Biophys Res Commun 339: 79-88, 2006.
27. Osburn WO, Yates MS, Dolan PD, Chen S, Liby KT, Sporn MB, Taguchi K, Yamamoto M, Kensler TW. Genetic or pharmacologic amplification of nrf2 signaling inhibits acute inflammatory liver injury in mice. Toxicol Sci 104: 218-227, 2008.
28. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29: 45, 2001.
29. Prestera T, Talalay P, Alam J, Ahn YI, Lee PJ, Choi AM. Parallel induction of heme oxygenase-1 and chemoprotective phase 2 enzymes by electrophiles and antioxidants: regulation by upstream antioxidant-responsive elements (ARE). Mol Med 1: 827-837, 1995.
30. Reisman SA, Csanaky IL, Yeager RL, Klaassen CD. Nrf2 activation enhances biliary excretion of sulfobromophthalein by inducing glutathione- S-transferase activity. Toxicol Sci 109: 24-30, 2009.
31. Soroka CJ, Lee JM, Azzaroli F, Boyer JL. Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver. Hepatology 33: 783-791, 2001.
32. Soroka CJ, Mennone A, Hagey LR, Ballatori N, Boyer JL. Mouse organic solute transporter-α deficiency enhances renal excretion of bile acids and attenuates cholestasis. Hepatology 51: 181-190, 2010.
33. Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, Liu Y, Klaassen CD, Brown KK, Reinhard J, Willson TM, Koller BH, Kliewer SA. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci USA 98: 3369-3374, 2001.
34. Sugimoto H, Okada K, Shoda J, Warabi E, Ishige K, Ueda T, Taguchi K, Yanagawa T, Nakahara A, Hyodo I, Ishii T, Yamamoto M. Deletion of nuclear factor-E2-related factor-2 leads to rapid onset and progression of nutritional steatohepatitis in mice. Am J Physiol Gastrointest Liver Physiol 298: G283-G294, 2010.
35. Tan KP, Wood GA, Yang M, Ito S. Participation of nuclear factor (erythroid 2-related) factor 2 in ameliorating lithocholic acid-induced cholestatic liver injury in mice. Br J Pharmacol 161: 1111-1121, 2010.
36. Tan KP, Yang M, Ito S. Activation of nuclear factor (erythroid-2 like) factor 2 by toxic bile acids provokes adaptive defense responses to enhance cell survival at the emergence of oxidative stress. Mol Pharmacol 72: 1380-1390, 2007.
37. Tanaka Y, Aleksunes LM, Cui YJ, Klaassen CD. ANIT-induced intrahepatic cholestasis alters hepatobiliary transporter expression via Nrf2- dependent and independent signaling. Toxicol Sci 108: 247-257, 2009.
38. Wagner M, Fickert P, Zollner G, Fuchsbichler A, Silbert D, Tsybrovskyy O, Zatloukal K, Guo GL, Schuetz JD, Gonzalez FJ, Marschall HU, Denk H, Trauner M. Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated mice. Gastroenterology 125: 825-838, 2003.
39. Wagner M, Halilbasic E, Marschall HU, Zollner G, Fickert P, Langner C, Zatloukal K, Denk H, Trauner M. CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice. Hepatology 42: 420-430, 2005.
40. Wagner M, Zollner G, Trauner M. Nuclear receptor regulation of the adaptive response of bile acid transporters in cholestasis. Semin Liver Dis 30: 160-177, 2010.
41. Wang W, Soroka CJ, Mennone A, Rahner C, Harry K, Pypaert M, Boyer JL. Radixin is required to maintain apical canalicular membrane structure and function in rat hepatocytes. Gastroenterology 131: 878-884, 2006.
42. Weerachayaphorn J, Cai SY, Soroka CJ, Boyer JL. Nuclear factor erythroid 2-related factor 2 is a positive regulator of human bile salt export pump expression. Hepatology 50: 1588-1596, 2009.
43. Weerachayaphorn J, Luo Y, Mennone A, Soroka CJ, Harry K, Boyer JL. Oltipraz, an Nrf2 activator, aggravates liver injury in a mouse model of extrahepatic cholestasis (Abstract). Hepatology Suppl 52: 665A, 2010.
44. Xie W, Radominska-Pandya A, Shi Y, Simon CM, Nelson MC, Ong ES, Waxman DJ, Evans RM. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci USA 98: 3375-3380, 2001.
45. Yang H, Ko K, Xia M, Li TW, Oh P, Li J, Lu SC. Induction of avian musculoaponeurotic fibrosarcoma proteins by toxic bile acid inhibits expression of glutathione synthetic enzymes and contributes to cholestatic liver injury in mice. Hepatology 51: 1291-1301, 2010.
46. Yang H, Ramani K, Xia M, Ko KS, Li TW, Oh P, Li J, Lu SC. Dysregulation of glutathione synthesis during cholestasis in mice: molecular mechanisms and therapeutic implications. Hepatology 49: 1982-1991, 2009.
47. Zhang M, Chiang JY. Transcriptional regulation of the human sterol 12α-hydroxylase gene (CYP8B1): roles of heaptocyte nuclear factor 4α in mediating bile acid repression. J Biol Chem 276: 41690-41699, 2001.
48. Zhang Y, Klaassen CD. Effects of feeding bile acids and a bile acid sequestrant on hepatic bile acid composition in mice. J Lipid Res 51: 3230-3242, 2010.
49. Zhang YK, Guo GL, Klaassen CD. Diurnal variations of mouse plasma and hepatic bile acid concentrations as well as expression of biosynthetic enzymes and transporters. PLos One 6: e16683, 2011.