Peroxisome proliferator-activated receptor-α signaling in hepatocarcinogenesis

Subcellular Biochemistry

Volumn 69, Issue , 2013, Pages 77-99

  Misra, Parimal ^a   Viswakarma, Navin ^b   Reddy, Janardan K ^c  

^a UNIVERSITY OF HYDERABAD   (India)

^b LOYOLA UNIVERSITY CHICAGO   (United States)

^c NORTHWESTERN UNIVERSITY   (United States)

Author keywords

Fatty acid oxidation; Hepatocarcinogenesis; Hepatocellular proliferation; Med1 subunit of Mediator complex; Oxidative stress; Peroxisome proliferators; Peroxisomes; PPAR signaling

Indexed keywords

FATTY ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA;

ANIMAL; CELL TRANSFORMATION; ENERGY METABOLISM; GENE EXPRESSION REGULATION; GENETICS; HUMAN; KNOCKOUT MOUSE; LIVER; LIVER TUMOR; METABOLISM; MOUSE; OXIDATION REDUCTION REACTION; PATHOLOGY; PEROXISOME; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; CELL TRANSFORMATION, NEOPLASTIC; ENERGY METABOLISM; FATTY ACIDS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; LIVER; LIVER NEOPLASMS; MICE; MICE, KNOCKOUT; OXIDATION-REDUCTION; PEROXISOMES; PPAR ALPHA; SIGNAL TRANSDUCTION;

EID: 84895150976     PISSN: 03060225     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-94-007-6889-5_5     Document Type: Article

References (95)

1. Arnauld S, Fidaleo M, Clemencet MC, Chevillard G, Athias A, Gresti J, Wanders RJ, Latruffe N, Nicolas-Frances V, Mandard S (2009) Modulation of the hepatic fatty acid pool in peroxisomal 3-ketoacyl-CoA thiolase B-null mice exposed to the selective PPARalpha agonist Wy14,643. Biochimie 91:1376-1386
2. Ashby J, Brady A, Elcombe CR, Elliott BM, Ishmael J, Odum J, Tugwood JD, Kettle S, Purchase IF (1994) Mechanistically-based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis. Hum Exp Toxicol 13(Suppl 2):S1-S117
3. Baes M, Huyghe S, Carmeliet P, Declercq PE, Collen D, Mannaerts GP, Van Veldhoven PP (2000) Inactivation of the peroxisomal multifunctional protein-2 in mice impedes the degradation of not only 2-methyl-branched fatty acids and bile acid intermediates but also of very long chain fatty acids. J Biol Chem 275:16329-16336
4. Bai L, Jia Y, Viswakarma N, Huang J, Vluggens A, Wolins NE, Jafari N, Rao MS, Borensztajn J, Yang G, Reddy JK (2011) Transcription coactivator mediator subunit MED1 is required for the development of fatty liver in the mouse. Hepatology 53:1164-1174
5. Brandt JM, Djouadi F, Kelly DP (1998) Fatty acids activate transcription of the muscle carnitine palmitoyltransferase I gene in cardiac myocytes via the peroxisome proliferator-activated receptor alpha. J Biol Chem 273:23786-23792
6. Caira F, Cherkaoui-Malki M, Hoefler G, Latruffe N (1996) Cloning and tissue expression of two cDNAs encoding the peroxisomal 2-enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in the guinea pig liver. FEBS Lett 378:57-60
7. Caira F, Clémencet MC, Cherkaoui-Malki M, Dieuaide-Noubhani M, Pacot C, Van Veldhoven PP, Latruffe N (1998) Differential regulation by a peroxisome proliferator of the different multifunctional proteins in guinea pig: cDNA cloning of the guinea pig D-specific multifunctional protein 2. Biochem J 330(Pt 3):1361-1368
8. Castillo MC, Sandalio LM, del Río LA, Léon J (2008) Peroxisome proliferation, wound-activated responses and expression of peroxisome-associated genes are cross-regulated but uncoupled in Arabidopsis thaliana. Plant Cell Environ 31:492-505
9. Chen Z, Zhang C, Wu D, Chen H, Rorick A, Zhang X, Wang Q (2011) Phospho-MED1-enhanced UBE2C locus looping drives castration-resistant prostate cancer growth. EMBO J 30:2405- 2419
10. Chevillard G, Clemencet MC, Latruffe N, Nicolas-Frances V (2004) Targeted disruption of the peroxisomal thiolase B gene in mouse: a new model to study disorders related to peroxisomal lipid metabolism. Biochimie 86:849-856
11. Crawford SE, Qi C, Misra P, Stellmach V, Rao MS, Engel JD, Zhu Y, Reddy JK (2002) Defects of the heart, eye, and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of transcription factors. J Biol Chem 277:3585-3592
12. David RM, Moore MR, Cifone MA, Finney DC, Guest D (1999) Chronic peroxisome proliferation and hepatomegaly associated with the hepatocellular tumorigenesis of di(2- ethylhexyl)phthalate and the effects of recovery. Toxicol Sci 50:195-205
13. De Duve C, Baudhuin P (1966) Peroxisomes (microbodies and related particles). Physiol Rev 46:323-357
14. Desvergne B, Wahli W (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 20:649-688
15. Dieuaide-Noubhani M, Novikov D, Baumgart E, Vanhooren JC, Fransen M, Goethals M, Vandekerckhove J, Van Veldhoven PP, Mannaerts GP (1996) Further characterization of the peroxisomal 3-hydroxyacyl-CoA dehydrogenases from rat liver. Relationship between the different dehydrogenases and evidence that fatty acids and the C27 bile acids di- and trihydroxycoprostanic acids are metabolized by separate multifunctional proteins. Eur J Biochem 240:660-666
16. Dieuaide-Noubhani M, Asselberghs S, Mannaerts GP, Van Veldhoven PP (1997) Evidence that multifunctional protein 2, and not multifunctional protein 1, is involved in the peroxisomal beta oxidation of pristanic acid. Biochem J 325(Pt 2):367-373
17. Fan C-Y, Pan J, Chu R, Lee D, Kluckman KD, Usuda N, Singh I, Yeldandi AV, Rao MS, Maeda N, Reddy JK (1996) Hepatocellular and hepatic peroxisomal alterations in mice with a disrupted peroxisomal fatty acyl-coenzyme A oxidase gene. J Biol Chem 271:24698-24710
18. Fan C-Y, Pan J, Usuda N, Yeldandi AV, Rao MS, Reddy JK (1998) Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase: implications for peroxisome proliferators activated receptor ' natural ligand metabolism. J Biol Chem 273:15639-15645
19. Ferdinandusse S, Denis S, Van Roermund CW,Wanders RJ, Dacremont G (2004) Identification of the peroxisomal beta-oxidation enzymes involved in the degradation of long-chain dicarboxylic acids. J Lipid Res 45:1104-1111
20. Gottlicher M, Widmark E, Li Q, Gustafsson JA (1992) Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc Natl Acad Sci USA 1992(89):4653-4657
21. Guo D, Sarkar J, Ahmed MR, Viswakarma N, Jia Y, Yu S, Sambasiva Rao M, Reddy JK (2006) Peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP) but not PPARinteracting protein (PRIP) is required for nuclear translocation of constitutive androstane receptor in mouse liver. Biochem Biophys Res Commun 347:485-495
22. Hashimoto T, Fujita T, Usuda N, Cook W, Qi C, Peters JM, Gonzalez FJ, Yeldandi AV, Rao MS, Reddy JK (1999) Peroxisomal and mitochondrial fatty acid beta-oxidation in mice nullizygous for both peroxisome proliferator-activated receptor alpha and peroxisomal fatty acyl-CoA oxidase. Genotype correlation with fatty liver phenotype. J Biol Chem 274:19228-19236
23. Houten SM, Denis S, Argmann CA, Jia Y, Ferdinandusse S, Reddy JK, Wanders RJ (2012) Peroxisomal L-bifunctional enzyme (Ehhadh) is essential for the production of medium-chain dicarboxylic acids. J Lipid Res 53:1296-1303
24. Huang J, Viswakarma N, Yu S, Jia Y, Bai L, Vluggens A, Cherkaoui-Malki M, Khan M, Singh I, Yang G, Rao MS, Borensztajn J, Reddy JK (2011) Progressive endoplasmic reticulum stress contributes to hepatocarcinogenesis in fatty acyl-CoA oxidase 1-deficient mice. Am J Pathol 179:703-713
25. Huang J, Jia Y, Fu T, Viswakarma N, Bai L, Rao MS, Zhu Y, Borensztajn J, Reddy JK (2012) Sustained activation of PPAR' by endogenous ligands increases hepatic fatty acid oxidation and prevents obesity in ob/ob mice. FASEB J 26:628-638
26. Issemann I, Green S (1990) Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347:645-650
27. Jia Y, Qi C, Zhang Z, Hashimoto T, Rao MS, Huyghe S, Suzuki Y, VanVeldhoven PP, Baes M, Reddy JK (2003) Overexpression of peroxisome proliferator-activated receptor-' (PPAR')- regulated genes in liver in the absence of peroxisome proliferation in mice deficient in both L and D-forms of enoyl-CoA hydratase/dehydrogenase enzymes of peroxisomal ß-oxidation system. J Biol Chem 2003(278):47232-47239
28. Jia Y, Qi C, Kashireddi P, Surapureddi S, Zhu YJ, Rao MS, Le Roith D, Chambon P, Gonzalez FJ, Reddy JK (2004) Transcription coactivator PBP, the peroxisome proliferator-activated receptor (PPAR)-binding protein, is required for PPAR'-regulated gene expression in liver. J Biol Chem 279:24427-24434
29. Jia Y, Guo GL, Surapureddi S, Sarkar J, Qi C, Guo D, Xia J, Kashireddi P, Yu S, Cho YW, Rao MS, Kemper B, Ge K, Gonzalez FJ, Reddy JK (2005) Transcription coactivator peroxisome proliferator-activated receptor-binding protein/mediator 1 deficiency abrogates acetaminophen hepatotoxicity. Proc Natl Acad Sci USA 102:12531-12536
30. Jia Y, Viswakarma N, Fu T, Yu S, Rao MS, Borensztajn J, Reddy JK (2009) Conditional ablation of mediator subunit MED1 (MED1/PPARBP) gene in mouse liver attenuates glucocorticoid receptor agonist dexamethasone-induced hepatic steatosis. Gene Expr 14:291-306
31. Jia Y, Viswakarma N, Crawford SE, Sarkar J, Sambasiva Rao M, Karpus WJ, Kanwar YS, Zhu YJ, Reddy JK (2012) Early embryonic lethality of mice with disrupted transcription cofactor PIMT/NCOA6IP/Tgs1 gene. Mech Dev 129:193-207
32. Kliewer SA, Umesono K, Noonan DJ, Heyman RA, Evans RM (1992) Convergence of 9-cis retinoic acid and peroxisome proliferator signaling pathways through heterodimer formation of their receptors. Nature 358:771-774
33. Kluwe WM, McConnell EE, Huff JE, Haseman JK, Douglas JF, Hartwell WV (1982) Carcinogenicity testing of phthalate esters and related compounds by the National Toxicology Program and the National Cancer Institute. Environ Health Perspect 45:129-133
34. Kornberg RD (2007) The molecular basis of eukaryotic transcription. Proc Natl Acad Sci USA 104:12955-12961
35. Lalwani ND, Reddy MK, Qureshi SA, Sirtori CR, Abiko Y, Reddy JK (1983) Evaluation of selected hypolipidemic agents for the induction of peroxisomal enzymes and peroxisome proliferation in rat liver. Hum Toxicol 2:27-48
36. Lalwani ND, Alvares K, Reddy MK, Reddy MN, Parikh I, Reddy JK (1987) Peroxisome proliferator binding protein: identification and partial characterization of nafenopin-, clofibric acid-, and ciprofibrate binding proteins from rat liver. Proc Natl Acad Sci USA 84:5142-5146
37. Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM, Westphal H, Gonzalez FJ (1995) Targeted disruption of the alpha isoform of the peroxisome proliferatoractivated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol 15:3012-3022
38. Mannaerts GP, van Veldhoven PP (1996) Functions and organization of peroxisomal betaoxidation. Ann N Y Acad Sci 804:99-115
39. Matsumoto K, Yu S, Jia Y, Ahmed MR, Viswakarma N, Sarkar J, Kashireddy PV, Rao MS, KarpusW, Gonzalez FJ, Reddy JK (2007) Critical role for transcription coactivator peroxisome proliferator-activated receptor (PPAR)-binding protein/TRAP220 in liver regeneration and PPARalpha ligand-induced liver tumor development. J Biol Chem 282:17053-17060
40. Meyer K, Lee JS, Dyck PA, Cao WQ, Rao MS, Thorgeirsson SS, Reddy JK (2003) Molecular profiling of hepatocellular carcinomas developing spontaneously in acyl-CoA oxidase deficient mice: comparison with liver tumors induced in wild-type mice by a peroxisome proliferator and a genotoxic carcinogen. Carcinogenesis 24:975-984
41. Misra P, Qi C, Yu S, Shah SH, Cao WQ, Rao MS, Thimmapaya B, Zhu Y, Reddy JK (2002a) Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation. J Biol Chem 277:20011-20019
42. Misra P, Owuor ED, Li W, Yu S, Qi C, Meyer K, Zhu YJ, Rao MS, Kong AN, Reddy JK (2002b) Phosphorylation of transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP). Stimulation of transcriptional regulation by mitogenactivated protein kinase. J Biol Chem 277:48745-48754
43. Mouaikel J, Verheggen C, Bertrand E, Tazi J, Bordonné R (2002) Hypermethylation of the cap structure of both yeast snRNAs and snoRNAs requires a conserved methyltransferase that is localized to the nucleolus. Mol Cell 9:891-901
44. Nila AG, Sandalio LM, López MG, Gómez M, del Río LA, Gómez-Lim MA (2006) Expression of a peroxisome proliferator-activated receptor gene (xPPAR) from Xenopus laevis in tobacco (Nicotiana tabacum) plants. Planta 224:569-581
45. Novikov DK, Vanhove GF, Carchon H, Asselberghs S, Eyssen HJ, Van Veldhoven PP, Mannaerts GP (1994) Peroxisomal beta-oxidation. Purification of four novel 3-hydroxyacyl-CoA dehydrogenases from rat liver peroxisomes. J Biol Chem 269:27125-27135
46. Osumi T, Hashimoto T (1980) Purification and properties of mitochondrial and peroxisomal 3- hydroxyacyl-CoA dehydrogenase from rat liver. Arch Biochem Biophys 203:372-383
47. Osumi T, Ishii N, Hijikata M, Kamijo K, Ozasa H, Furuta S, Miyazawa S, Kondo K, Inoue K, Kagamiyama H, Hashimoto T (1985) Molecular cloning and nucleotide sequence of the cDNA for rat peroxisomal enoyl-CoA: hydratase-3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme. J Biol Chem 260:8905-8910
48. Palma JM, Garrido M, Rodríguez-Garcia MI, del Río LA (1991) Peroxisome proliferation and oxidative stress mediated by activated oxygen species in plant peroxisomes. Arch Biochem Biophys 287:68-74
49. Palosaari PM, Hiltunen JK (1990) Peroxisomal bifunctional protein from rat liver is a trifunctional enzyme possessing 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2- enoyl-CoA isomerase activities. J Biol Chem 265:2446-2449
50. Peters JM, Cattley RC, Gonzalez FJ (1997) Role of PPAR alpha in the mechanism of action of the nongenotoxic carcinogen and peroxisome proliferator Wy-14,643. Carcinogenesis 18: 2029-2033
51. Peters JM, Lee SS, Li W, Ward JM, Gavrilova O, Everett C, Reitman ML, Hudson LD, Gonzalez FJ (2000) Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor ßd. Mol Cell Biol 20:5119-5128
52. Peters JM, Shah YM, Gonzalez FJ (2012) The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention. Nat Rev Cancer 12:181-195
53. Poll-The BT, Roels F, Ogier H, Scotto J, Vamecq J, Schutgens RB, Wanders RJ, van Roermund CW, van Wijland MJ, Schram AW, Tager JM, Saudubray J-M (1988) A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudoneonatal adrenoleukodystrophy). Am J Hum Genet 42:422-434
54. Pyper SR, Viswakarma N, Yu S, Reddy JK (2010) PPARalpha: energy combustion, hypolipidemia, inflammation and cancer. Nucl Recept Signal. doi:10.1621/nrs.08002
55. Qi C, Zhu Y, Pan J, Usuda N, Maeda N, Yeldandi AV, Rao MS, Hashimoto T, Reddy JK (1999) Absence of spontaneous peroxisome proliferation in enoyl-CoA hydratase/L-3-hydroxyacyl- CoA dehydrogenase-deficient mouse liver: further support for the role of fatty acyl- CoA oxidase in PPAR' ligand metabolism. J Biol Chem 274:15775-15780
56. Qin YM, Poutanen MH, Helander HM, Kvist AP, Siivari KM, SchmitzW, Conzelmann E, Hellman U, Hiltunen JK (1997) Peroxisomal multifunctional enzyme of beta-oxidation metabolizing D-3-hydroxyacyl-CoA esters in rat liver: molecular cloning, expression and characterization. Biochem J 321:21-28
57. Rao MS, Reddy JK (1987) Peroxisome proliferation and hepatocarcinogenesis. Carcinogenesis 8:631-636
58. Rao MS, Lalwani ND, Scarpelli DG, Reddy JK (1982) The absence of ?-glutamyl transpeptidase activity in putative preneoplastic lesions and in hepatocellular carcinomas induced in rats by the hypolipidemic peroxisome proliferator Wy-14,643. Carcinogenesis 3:1231-1233
59. RaoMS, Lalwani ND,Watanabe TK, Reddy JK (1984) Inhibitory effect of antioxidants ethoxyquin and 2(3)-tert-butyl-4-hydroxyanisole on hepatic tumorigenesis in rats fed ciprofibrate, a peroxisome proliferator. Cancer Res 44:1072-1076
60. Reddy JK (2004) Peroxisome proliferators and peroxisome proliferator-activated receptor ': biotic and xenobiotic sensing. Am J Pathol 164:2305-2321
61. Reddy JK, Chu R (1996) Peroxisome proliferator-induced pleiotropic responses: pursuit of a phenomenon. Ann N Y Acad Sci 804:176-201
62. Reddy JK, Hashimoto T (2001) Peroxisomal beta-oxidation and peroxisome proliferator-activated receptor alpha: an adaptive metabolic system. Annu Rev Nutr 21:193-230
63. Reddy JK, Krishnakantha TP (1975) Hepatic peroxisome proliferation: induction by two novel compounds structurally unrelated to clofibrate. Science 190:787-789
64. Reddy JK, Lalwani ND (1983a) Carcinogenesis by hepatic peroxisome proliferators: evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans. Crit Rev Toxicol 12:1-58
65. Reddy JK, Lalwani ND (1983b) Carcinogenesis by hepatic peroxisome proliferators: evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans. CRC Crit Rev Toxicol 12:1-58
66. Reddy JK, Mannaerts GP (1994) Peroxisomal lipid metabolism. Annu Rev Nutr 14:343-370
67. Reddy JK, Qureshi SA (1979) Tumorigenicity of the hypolipidaemic peroxisome proliferator ethyl-alpha-p-chlorophenoxyisobutyrate (clofibrate) in rats. Br J Cancer 40:476-482
68. Reddy JK, Rao MS (1977) Malignant tumors in rats fed nafenopin, a hepatic peroxisome proliferator. J Natl Cancer Inst 59:1645-1650
69. Reddy JK, Rao MS (1986) Peroxisome proliferators and cancer: mechanisms and implications. Trends Pharmacol Sci 7:438-443
70. Reddy JK, RaoMS (1988) Peroxisome proliferation-related oxidative stress and hepatocarcinogenesis. In: Cerutti PA, Nygaard AF, Simic MG (eds) Anticarcinogenesis and radiation protection, 1st edn. Springer, New York
71. Reddy JK, Rao MS (2006) Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol 290:G852-G858
72. Reddy JK, Rao MS, Moody DE (1976) Hepatocellular carcinomas in acatalasemic mice treated with nafenopin, a hypolipidemic peroxisome proliferator. Cancer Res 36:1211-1217
73. Reddy JK, Rao MS, Azarnoff DL, Sell S (1979) Mitogenic and carcinogenic effects of a hypolipidemic peroxisome proliferator, [4-chloro-6-(2, 3-xylidino)-2-pyrimidinylthio] acetic acid (Wy-14,643) in rat and mouse liver. Cancer Res 39:152-161
74. Reddy JK, Azarnoff DL, Hignite CE (1980) Hypolipidaemic hepatic peroxisome proliferators form a novel class of chemical carcinogens. Nature 283:397-398
75. Reddy JK, Lalwani ND, ReddyMK, Qureshi SA (1982) Excessive accumulation of autofluorescent lipofuscin in the liver during hepatocarcinogenesis by methyl clofenapate and other hypolipidemic peroxisome proliferators. Cancer Res 42:259-266
76. Reddy JK, Goel SK, Nemali MR, Carrino JJ, Laffler TG, Reddy MK, Sperbeck SJ, Osumi T, Hashimoto T, Lalwani ND, Rao MS (1986) Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators. Proc Natl Acad Sci USA 83:1747-1751
77. Rusyn I, Asakura S, Pachkowski B, Bradford BU, Denissenko MF, Peters JM, Holland SM, Reddy JK, Cunningham ML, Swenberg JA (2004) Expression of base excision DNA repair genes is a sensitive biomarker for in vivo detection of chemical-induced chronic oxidative stress: identification of the molecular source of radicals responsible for DNA damage by peroxisome proliferators. Cancer Res 64:1050-1057
78. Seedorf U, Raabe M, Ellinghaus P, Kannenberg F, Fobker M, Engel T, Denis S, Wouters F, Wirtz KW,Wanders RJ, Maeda N, Assmann G (1988) Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function. Genes Dev 12:1189-1201
79. Seedorf U, Brysch P, Engel T, Schrage K, Assmann G (1994) Sterol carrier protein X is peroxisomal 3-oxoacyl coenzyme A thiolase with intrinsic sterol carrier and lipid transfer activity. J Biol Chem 269:21277-21283
80. Shah YM, Morimura K, Yang Q, Tanabe T, TakagiM, Gonzalez FJ (2007) Peroxisome proliferatoractivated receptor alpha regulates a microRNA-mediated signaling cascade responsible for hepatocellular proliferation. Mol Cell Biol 27:4238-4247
81. Steinberg SJ, Morgenthaler J, Heinzer AK, Smith KD, Watkins PA (2000) Very long-chain acyl-CoA synthetases. Human "bubblegum" represents a new family of proteins capable of activating very long-chain fatty acids. J Biol Chem 275:35162-35169
82. Tolbert NE (1981) Metabolic pathways in peroxisomes and glyoxysomes. Annu Rev Biochem 50:133-157
83. Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM (1994) mPPAR?2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 8:1224-1234
84. Tyra HM, Spitz DR, Rutkowski DT (2012) Inhibition of fatty acid oxidation enhances oxidative protein folding and protects hepatocytes from endoplasmic reticulum stress. Mol Biol Cell 23:811-819
85. Viswakarma N, Jia Y, Bai L, Vluggens A, Borensztajn J, Xu J, Reddy JK (2010) Coactivators in PPAR-regulated gene expression. PPAR Res. doi:pii:250126.10.1155/2010/250126
86. von den Bosch H, Schutgens RB, Wanders RJ, Tager JM (1992) Biochemistry of peroxisomes. Annu Rev Biochem 61:157-197
87. Wanders RJ, Vreken P, Ferdinandusse S, Jansen GA, Waterham HR, Van Roermund CWT, Van Grunsven EG (2001) Peroxisomal fatty acid '- and ß-oxidation in humans: enzymology, peroxisomal metabolite transporters, and peroxisomal diseases. Biochem Soc Trans 29(Pt 2):250-267
88. Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM (2003) Peroxisome proliferatoractivated receptor &activates fat metabolism to prevent obesity. Cell 113:159-170
89. Warren JR, Simmon VF, Reddy JK (1980) Properties of hypolipidemic peroxisome proliferators in the lymphocyte (3H)thymidine and Salmonella mutagenesis assays. Cancer Res 40:36-41
90. Weisburger JH, Williams GM (2000) The distinction between genotoxic and epigenetic carcinogens and implication for cancer risk. Toxicol Sci 57:4-5
91. Xu R, Cuebas DA (1996) The reactions catalyzed by the inducible bifunctional enzyme of rat liver peroxisomes cannot lead to the formation of bile acids. Biochem Biophys Res Commun 221:271-278
92. Yeldandi AV, RaoMS, Reddy JK (2000) Hydrogen peroxide generation in peroxisome proliferatorinduced oncogenesis. Mutat Res 448:159-177
93. Zhu Y, Qi C, Korenberg JR, Chen X-N, Noya D, Rao MS, Reddy JK (1995) Structural organization of mouse peroxisome proliferator-activated receptor ? (mPPAR?) gene: alternative promoter use and different splicing yield two mPPAR? isoforms. Proc Natl Acad Sci USA 92: 7921-7925
94. Zhu Y, Qi C, Jia Y, Nye JS, Rao MS, Reddy JK (2000) Deletion of PBP/PPARBP, the gene for nuclear receptor coactivator peroxisome proliferator-activated receptor-binding protein, results in embryonic lethality. J Biol Chem 275:14779-14782
95. Zhu Y, Qi C, Cao WQ, Yeldandi AV, Rao MS, Reddy JK (2001) Cloning and characterization of PIMT, a protein with a methyltransferase domain, which interacts with and enhances nuclear receptor coactivator PRIP function. Proc Natl Acad Sci USA 18:10380-10385