RXR activators molecular signalling: Involvement of a PPARα-dependent pathway in the liver and kidney, evidence for an alternative pathway in the heart

British Journal of Pharmacology

Volumn 138, Issue 5, 2003, Pages 845-854

  Ouamrane, Laïla ^a,b   Larrieu, Gilberte ^a   Gauthier, Béatrice ^b   Pineau, Thierry ^a  

^a CEMAGREF   (France)

^b Galderma R and D   (France)

Author keywords

Fibrate; Heart; Kidney; Liver; Nuclear receptor; PPAR; Pyruvate dehydrogenase kinase; Retinoid; Rexinoid; RXR

Indexed keywords

6 [1 (5,6,7,8 TETRAHYDRO 3,5,5,8,8 PENTAMETHYL 2 NAPHTHYL)CYCLOPROPYL]NICOTINIC ACID; BEXAROTENE; FENOFIBRATE; FIBRIC ACID DERIVATIVE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; RETINOIC ACID; RETINOID X RECEPTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; DRUG EFFICACY; DRUG STRUCTURE; GENE ACTIVATION; GENE EXPRESSION; GENETIC TRANSCRIPTION; HEART; HYPERLIPIDEMIA; KIDNEY; LIVER; LIVER CELL; MALE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; RABBIT; RAT; RECEPTOR UPREGULATION; SIGNAL TRANSDUCTION; SKIN DISEASE; SPECIES DIFFERENCE;

ANIMALS; CELLS, CULTURED; FEMALE; HEART; HUMANS; KIDNEY; LIVER; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; RABBITS; RATS; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, RETINOIC ACID; RETINOID X RECEPTORS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 0037350669     PISSN: 00071188     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.bjp.0705113     Document Type: Article

References (49)

1. ALDRIDGE, T.C., TUGWOOD, J.D. & GREEN, S. (1995). Identification and characterization of DNA elements implicated in the regulation of CYP4A1 transcription. Biochem. J., 306, 473-479.
2. ANDERSON, S.P., CATTLEY, R.C. & CORTON, J.C. (1999). Hepatic expression of acute-phase protein genes during carcinogenesis induced by peroxisome proliferators. Mol. Carcinog., 26, 226-238.
3. ARANDA, A. & PASCUAL, A. (2001). Nuclear hormone receptors and gene expression. Physiol. Rev., 81, 1269-1304.
4. BOEHM, M.F., HEYMAN, R.A., PATEL, S., STEIN, R. & NAGPAL, S. (1995). Retinoids: biological function and use in the treatment of dermatological diseases. Exp. Opin. Invest. Drugs, 4, 593-612.
5. BRAISSANT, O., FOUFELLE, F., SCOTTO, C., DAUCA, M. & WAHLI, W. (1996). Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology, 137, 354-366.
6. CLAUDEL, T., LEIBOWITZ, M.D., FIEVET, C., TAILLEUX, A., WAGNER, B., REPA, J.J., TORPIER, G., LOBACCARO, J.M., PATERNITI, J.R., MANGELSDORF, D.J., HEYMAN, R.A. & AUWERX, J. (2001). Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor. Proc. Natl. Acad. Sci. U.S.A., 98, 2610-2615.
7. COSTET, P., LEGENDRE, C., MORE, J., EDGAR, A., GALTIER, P. & PINEAU, T. (1998). Peroxisome proliferator-activated receptor alpha-isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis. J. Biol. Chem., 273, 29577-29585.
8. DAUJAT, M., PICHARD, L., DALET, C., LARROQUE, C., BONFILS, C., POMPON, D., LI, D., GUZELIAN, P.S. & MAUREL, P. (1987). Expression of five forms of microsomal cytochrome P-450 in primary cultures of rabbit hepatocytes treated with various classes of inducers. Biochem. Pharmacol., 36, 3597-3606.
9. DAVIES, P.J., BERRY, S.A., SHIPLEY, G.L., ECKEL, R.H., HENNUYER, N., CROMBIE, D.L., OGILVIE, K.M., PEINADO-ONSURBE, J., FIEVET, C., LEIBOWITZ, M.D., HEYMAN, R.A. & AUWERX, J. (2001). Metabolic effects of rexinoids: tissue-specific regulation of lipoprotein lipase activity. Mol. Pharmacol., 59, 170-176.
10. DIRVEN, H.A., VAN DEN BROEK, P.H., PEETERS, M.C., PETERS, J.G., MENNES, W.C., BLAAUBOER, B.J., NOORDHOEK, J. & JONGENEELEN, F.J. (1993). Effects of the peroxisome proliferator mono(2-ethylhexyl)phthalate in primary hepatocyte cultures derived from rat, guinea pig, rabbit and monkey. Relationship between interspecies differences in biotransformation and peroxisome proliferating potencies. Biochem. Pharmacol., 45, 2425-2434.
11. DJOUADI, F., BRANDT, J.M., WEINHEIMER, C.J., LEONE, T.C., GONZALEZ, F.J. & KELLY, D.P. (1999). The role of the peroxisome proliferator-activated receptor alpha (PPAR alpha) in the control of cardiac lipid metabolism. Prostaglandins Leukot. Essent. Fatty Acids, 60, 339-343.
12. ELCOMBE, C.R. & MITCHELL, A.M. (1986). Peroxisome proliferation due to di(2-ethylhexyl) phthalate (DEHP): species differences and possible mechanisms. Environ. Health Perspect., 70, 211-219.
13. FORMAN, B.M., UMESONO, K., CHEN, J. & EVANS, R.M. (1995). Unique response pathways are established by allosteric interactions among nuclear hormone receptors. Cell. 81, 541-550.
14. GARIOT, P., BARRAT, E., DROUIN, P., GENTON, P., POINTEL, J.P., FOLIGUET, B., KOLOPP, M. & DEBRY, G. (1987). Morphometric study of human hepatic cell modifications induced by fenofibrate. Metabolism, 36, 203-210.
15. GARIOT, P., BARRAT, E., MEJEAN, L., POINTEL, J.P., DROUIN, P. & DEBRY, G. (1983). Fenofibrate and human liver. Lack of proliferation of peroxisomes. Arch. Toxicol., 53, 151-163.
16. GOMEZ-LECHON, M.J., LOPEZ, P. & CASTELL, J.V. (1984). Biochemical functionality and recovery of hepatocytes after deep freezing storage. In Vitro, 20, 826-832.
17. HOLNESS, M.J., BULMER, K., GIBBONS, G.F. & SUGDEN, M.C. (2002a). Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor alpha (PPARalpha). Biochem. J., 366, 839-846.
18. HOLNESS, M.J., SMITH, N.D., BULMER, K., HOPKINS, T., GIBBONS, G.F. & SUGDEN, M.C. (2002b). Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism. Biochem. J., 364, 687-694.
19. HUANG, B., WU, P., BOWKER-KINLEY, M.M. & HARRIS, R.A. (2002). Regulation of Pyruvate Dehydrogenase Kinase Expression by Peroxisome Proliferator-Activated Receptor-[alpha] Ligands, Glucocorticoids, and Insulin. Diabetes, 51, 276-283.
20. HURST, R.E. (2000). Bexarotene ligand pharmaceuticals. Curr. Opin. Investig. Drugs, 1, 514-523.
21. IMAI, T., JIANG, M., KASTNER, P., CHAMBON, P. & METZGER, D. (2001). Selective ablation of retinoid X receptor alpha in hepatocytes impairs their lifespan and regenerative capacity. Proc. Natl. Acad. Sci. U.S.A., 98, 4581-4586.
22. KASTNER, P., GRONDONA, J.M., MARK, M., GANSMULLER, A., LEMEUR, M., DECIMO, D., VONESCH, J.L., DOLLE, P. & CHAMBON, P. (1994). Genetic analysis of RXR-alpha developmental function: convergence of RXR and RAR signaling pathways in heart and eye morphogenesis. Cell, 78, 987-1003.
23. KLEIN, I. & OJAMAA, K. (2001). Thyroid hormone and the cardiovascular system. N. Engl. J. Med., 344, 501-509.
24. KLIEWER, S.A., FORMAN, B.M., BLUMBERG, B., ONG, E.S., BORGMEYER, U., MANGELSDORF, D.J., UMESONO, K. & EVANS, R.M. (1994). Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc. Natl. Acad. Sci. U.S.A., 91, 7355-7359.
25. LANSIAUX, A., FORMSTECHER, P. & BAILLY, C. (2000). [LGD1069: an antagonist to the X retinoid receptor]. Bull. Cancer, 87, 235-238.
26. LEE, S.S., PINEAU, T., DRAGO, J., LEE, E.J., OWENS, J.W., KROETZ, D.L., FERNANDEZ-SALGUERO, P.M., WESTPHAL, H. & GONZALEZ, F.J. (1995). Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol. Cell Biol., 15, 3012-3122.
27. LENHARD, J.M., LANCASTER, M.E., PAULIK, M.A., WEIEL, J.E., BINZ, J.G., SUNDSETH, S.S., GASKILL, B.A., LIGHTFOOT, R.M. & BROWN, H.R. (1999). The RXR agonist LG100268 causes hepatomegaly, improves glycaemic control and decreases cardiovascular risk and cachexia in diabetic mice suffering from pancreatic beta-cell dysfunction. Diabetologia, 42, 545-554.
28. LI, D., LI, T., WANG, F., TIAN, H. & SAMUELS, H.H. (2002). Functional evidence for retinoid X receptor (RXR) as a nonsilent partner in the thyroid hormone receptor/RXR heterodimer. Mol. Cell Biol., 22, 5782-5792.
29. MANGELSDORF, D.J. & EVANS, R.M. (1995). The RXR heterodimers and orphan receptors. Cell, 83, 841-850.
30. MANGELSDORF, D.J., THUMMEL, C., BEATO, M., HERRLICH, P., SCHUTZ, G., UMESONO, K., BLUMBERG, B., KASTNER, P., MARK, M., CHAMBON, P. & EVANS, R.M. (1995). The nuclear receptor superfamily: the second decade. Cell, 83, 835-839.
31. MUKHERJEE, R., DAVIES, P.J., CROMBIE, D.L., BISCHOFF, E.D., CESARIO, R.M., JOW, L., HAMANN, L.G., BOEHM, M.F., MONDON, C.E., NADZAN, A.M., PATERNITI, JR, J.R. & HEYMAN, R.A. (1997). Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature, 386, 407-410.
32. MUKHERJEE, R., STRASSER, J., JOW, L., HOENER, P., PATERNITI, JR, J.R. & HEYMAN, R.A. (1998). RXR agonists activate PPARalpha-inducible genes, lower triglycerides, and raise HDL levels in vivo. Arterioscler. Thromb. Vasc. Biol., 18, 272-276.
33. NAGPAL, S. & CHANDRARATNA, R.A. (2000). Recent developments in receptor-selective retinoids. Curr. Pharm. Des., 6, 919-931.
34. PETERS, J.M., AOYAMA, T., CATTLEY, R.C., NOBUMITSU, U., HASHIMOTO, T. & GONZALEZ, F.J. (1998). Role of peroxisome proliferator-activated receptor alpha in altered cell cycle regulation in mouse liver. Carcinogenesis, 19, 1989-1994.
35. PETERS, J.M., ZHOU, Y.C., RAM, P.A., LEE, S.S., GONZALEZ, F.J. & WAXMAN, D.J. (1996). Peroxisome proliferator-activated receptor alpha required for gene induction by dehydroepiandrosterone-3 beta-sulfate. Mol. Pharmacol., 50, 67-74.
36. RIZVI, N.A., MARSHALL, J.L., DAHUT, W., NESS, E., TRUGLIA, J.A., LOEWEN, G., GILL, G.M., ULM, E.H., GEISER, R., JAUNAKAIS, D. & HAWKINS, M.J. (1999). A Phase I study of LGD1069 in adults with advanced cancer. Clin. Cancer Res., 5, 1658-1664.
37. ROBERTS, R.A., JAMES, N.H., HASMALL, S.C., HOLDEN, P.R., LAMBE, K., MACDONALD, N., WEST, D., WOODYATT, N.J. & WHITCOME, D. (2000). Apoptosis and proliferation in non-genotoxic carcinogenesis: species differences and role of PPAR-alpha. Toxicol. Lett., 112-113, 49-57.
38. SEGLEN, P.O. (1976). Preparation of isolated rat liver cells. Methods Cell Biol., 13, 29-83.
39. STANDEVEN, A.M., BEARD, R.L., JOHNSON, A.T., BOEHM, M.F., ESCOBAR, M., HEYMAN, R.A. & CHANDRARATNA, R.A. (1996). Retinoid-induced hypertriglyceridemia in rats is mediated by retinoic acid receptors. Fundam. Appl. Toxicol., 33, 264-271.
40. STANDEVEN, A.M., ESCOBAR, M., BEARD, R.L., YUAN, Y.D. & CHANDRARATNA, R.A. (1997). Mitogenic effect of retinoid X receptor agonists in rat liver. Biochem. Pharmacol., 54, 517-524.
41. STANDEVEN, A.M., THACHER, S.M., YUAN, Y.D., ESCOBAR, M., VULIGONDA, V., BEARD, R.L. & CHANDRARATNA, R.A. (2001). Retinoid X receptor agonist elevation of serum triglycerides in rats by potentiation of retinoic acid receptor agonist induction or by action as single agents. Biochem. Pharmacol., 62, 1501-1519.
42. SUCOV, H.M., DYSON, E., GUMERINGER, C.L., PRICE, J., CHIEN, K.R. & EVANS, R.M. (1994). RXR alpha mutant mice establish a genetic basis for vitamin A signaling in heart morphogenesis. Genes Dev., 8, 1007-1018.
43. SUGDEN, M.C., BULMER, K., AUGUSTINE, D. & HOLNESS, M.J. (2001a). Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha: implications for glucose-stimulated insulin secretion. Diabetes, 50, 2729-2736.
44. SUGDEN, M.C., BULMER, K., GIBBONS, G.F. & HOLNESS, M.J. (2001b). Role of peroxisome proliferator-activated receptor-alpha in the mechanism underlying changes in renal pyruvate dehydrogenase kinase isoform 4 protein expression in starvation and after refeeding. Arch. Biochem. Biophys., 395, 246-252.
45. SUGDEN, M.C., BULMER, K. & HOLNESS, M.J. (2001c). Fuel-sensing mechanisms integrating lipid and carbohydrate utilization. Biochem. Soc. Trans., 29, 272-278.
46. TALPUR, R., WARD, S. APISARNTHANARAX, N., BREUERMCHAM, J. & DUVIC, M. (2002). Optimizing bexarotene therapy for cutaneous T-cell lymphoma. J. Am. Acad. Dermatol., 47, 672-684.
47. THACHER, S.M., VASUDEVAN, J. & CHANDRARATNA, R.A. (2000). Therapeutic applications for ligands of retinoid receptors. Curr. Pharm. Des., 6, 25-58.
48. WAN, Y.J., AN, D., CAI, Y., REPA, J.J., HUNG-PO CHEN, T., FLORES, M., POSTIC, C., MAGNUSON, M.A., CHEN, J., CHIEN, K.R., FRENCH, S., MANGELSDORF, D.J. & SUCOV, H.M. (2000). Hepatocyte-specific mutation establishes retinoid X receptor alpha as a heterodimeric integrator of multiple physiological processes in the liver. Mol. Cell Biol., 20, 4436-4444.
49. WU, P., PETERS, J.M. & HARRIS, R.A. (2001). Adaptive increase in pyruvate dehydrogenase kinase 4 during starvation is mediated by peroxisome proliferator-activated receptor alpha. Biochem. Biophys. Res. Commun., 287, 391-396.