Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2012, Article ID 504918, 16 pages
http://dx.doi.org/10.1155/2012/504918
Review Article

PPAR Medicines and Human Disease: The ABCs of It All

1Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada K7L 3N6
2Cancer Biology and Genetics Division, Cancer Research Institute, Queen's University, Kingston, ON, Canada K7L 3N6
3Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada K7L 3N6

Received 24 February 2012; Revised 4 April 2012; Accepted 6 April 2012

Academic Editor: Yuji Kamijo

Copyright © 2012 Anthony J. Apostoli and Christopher J. B. Nicol. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. N. S. Wind and I. Holen, “Multidrug resistance in breast cancer: from in vitro models to clinical studies,” International Journal of Breast Cancer, vol. 2011, Article ID 967419, 12 pages, 2011. View at Google Scholar
  2. A. J. Slot, S. V. Molinski, and S. P. Cole, “Mammalian multidrug-resistance proteins (MRPs),” Essays in Biochemistry, vol. 50, no. 1, pp. 179–207, 2011. View at Google Scholar
  3. R. G. Deeley, C. Westlake, and S. P. C. Cole, “Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins,” Physiological Reviews, vol. 86, no. 3, pp. 849–899, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Dean, A. Rzhetsky, and R. Allikmets, “The human ATP-binding cassette (ABC) transporter superfamily,” Genome Research, vol. 11, no. 7, pp. 1156–1166, 2001. View at Publisher · View at Google Scholar · View at Scopus
  5. D. C. Rees, E. Johnson, and O. Lewinson, “ABC transporters: the power to change,” Nature Reviews Molecular Cell Biology, vol. 10, no. 3, pp. 218–227, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. J. P. Berger, T. E. Akiyama, and P. T. Meinke, “PPARs: therapeutic targets for metabolic disease,” Trends in Pharmacological Sciences, vol. 26, no. 5, pp. 244–251, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. R. Kostadinova, W. Wahli, and L. Michalik, “PPARs in diseases: control mechanisms of inflammation,” Current Medicinal Chemistry, vol. 12, no. 25, pp. 2995–3009, 2005. View at Publisher · View at Google Scholar · View at Scopus
  8. J. M. Peters, Y. M. Shah, and F. J. Gonzalez, “The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention,” Nature Reviews Cancer, vol. 12, pp. 181–195, 2012. View at Google Scholar
  9. A. Montagner, G. Rando, G. Degueurce, N. Leuenberger, L. Michalik, and W. Wahli, “New insights into the role of PPARs,” Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 85, no. 5, pp. 235–243, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. Y. X. Wang, “PPARs: diverse regulators in energy metabolism and metabolic diseases,” Cell Research, vol. 20, no. 2, pp. 124–137, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. L. Michalik, J. Auwerx, J. P. Berger et al., “International union of pharmacology. LXI. Peroxisome proliferator-activated receptors,” Pharmacological Reviews, vol. 58, no. 4, pp. 726–741, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. T. M. Willson, P. J. Brown, D. D. Sternbach, and B. R. Henke, “The PPARs: from orphan receptors to drug discovery,” Journal of Medicinal Chemistry, vol. 43, no. 4, pp. 527–550, 2000. View at Publisher · View at Google Scholar · View at Scopus
  13. A. I. Shulman and D. J. Mangelsdorf, “Retinoid X receptor heterodimers in the metabolic syndrome,” New England Journal of Medicine, vol. 353, no. 6, pp. 604–615, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Ricote and C. K. Glass, “PPARs and molecular mechanisms of transrepression,” Biochimica et Biophysica Acta, vol. 1771, no. 8, pp. 926–935, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. D. Auboeuf, J. Rieusset, L. Fajas et al., “Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-α in humans: no alteration in adipose tissue of obese and NIDDM patients,” Diabetes, vol. 46, no. 8, pp. 1319–1327, 1997. View at Google Scholar · View at Scopus
  16. I. Issemann and S. Green, “Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators,” Nature, vol. 347, no. 6294, pp. 645–650, 1990. View at Publisher · View at Google Scholar · View at Scopus
  17. C. Pirat, A. Farce, N. Lebegue et al., “Targeting peroxisome proliferator-activated receptors (PPARs): development of modulators,” Journal of Medicinal Chemistry, vol. 55, no. 94, pp. 4027–4061, 2012. View at Google Scholar
  18. A. Chawla, E. J. Schwarz, D. D. Dimaculangan, and M. A. Lazar, “Peroxisome proliferator-activated receptor (PPAR) γ: adipose-predominant expression and induction early in adipocyte differentiation,” Endocrinology, vol. 135, no. 2, pp. 798–800, 1994. View at Publisher · View at Google Scholar · View at Scopus
  19. J. Plutzky, “Inflammation in atherosclerosis and diabetes mellitus,” Reviews in Endocrine and Metabolic Disorders, vol. 5, no. 3, pp. 255–259, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. M. Ricote, J. Huang, L. Fajas et al., “Expression of the peroxisome proliferator-activated receptor γ (PPARγ) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 13, pp. 7614–7619, 1998. View at Google Scholar · View at Scopus
  21. B. M. Spiegelman, “PPAR-γ: adipogenic regulator and thiazolidinedione receptor,” Diabetes, vol. 47, no. 4, pp. 507–514, 1998. View at Publisher · View at Google Scholar · View at Scopus
  22. G. Daniel, “Risk of cardiovascular events and all-cause mortality among commercially-insured patients treated with thiazolidinediones,” in Proceedings of the FDA Joint Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, July 2010.
  23. C. Piccinni, D. Motola, G. Marchesini, and E. Poluzzi, “Assessing the association of pioglitazone use and bladder cancer through drug adverse event reporting,” Diabetes Care, vol. 34, no. 6, pp. 1369–1371, 2011. View at Google Scholar
  24. J. Woodcock, J. M. Sharfstein, and M. Hamburg, “Regulatory action on rosiglitazone by the U.S. Food and Drug Administration,” New England Journal of Medicine, vol. 363, no. 16, pp. 1489–1491, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. “FDA Drug Safety Communication: Updated drug labels for pioglitazone-containing medicines,” http://www.fda.gov/Drugs/DrugSafety/ucm266555.htm.
  26. “Avandia (rosiglitazone): REMS—Risk of Cardiovascular Events,” http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm226994.htm?utm_source=fdaSearch&utm_medium=website&utm_term=rosiglitazone&utm_content=1%7D.
  27. E. Adeghate, A. Adem, M.Y. Hasan, K. Tekes, and H. Kalasz, “Medicinal chemistry and actions of dual and pan PPAR modulators,” The Open Medicinal Chemistry Journal, vol. 5, supplement 2, pp. 93–98, 2011. View at Google Scholar
  28. M. M. Gottesman, T. Fojo, and S. E. Bates, “Multidrug resistance in cancer: role of ATP-dependent transporters,” Nature Reviews Cancer, vol. 2, no. 1, pp. 48–58, 2002. View at Google Scholar · View at Scopus
  29. R. L. Juliano and V. Ling, “A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants,” Biochimica et Biophysica Acta, vol. 455, no. 1, pp. 152–162, 1976. View at Google Scholar · View at Scopus
  30. S. V. Ambudkar, C. Kimchi-Sarfaty, Z. E. Sauna, and M. M. Gottesman, “P-glycoprotein: from genomics to mechanism,” Oncogene, vol. 22, no. 47, pp. 7468–7485, 2003. View at Publisher · View at Google Scholar · View at Scopus
  31. E. Mechetner, A. Kyshtoobayeva, S. Zonis et al., “Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin,” Clinical Cancer Research, vol. 4, no. 2, pp. 389–398, 1998. View at Google Scholar · View at Scopus
  32. C. Atalay, I. D. Gurhan, C. Irkkan, and U. Gunduz, “Multidrug resistance in locally advanced breast cancer,” Tumor Biology, vol. 27, no. 6, pp. 309–318, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. J. I. Fletcher, M. Haber, M. J. Henderson, and M. D. Norris, “ABC transporters in cancer: more than just drug efflux pumps,” Nature Reviews Cancer, vol. 10, no. 2, pp. 147–156, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. S. P. C. Cole, G. Bhardwaj, J. H. Gerlach et al., “Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line,” Science, vol. 258, no. 5088, pp. 1650–1654, 1992. View at Google Scholar · View at Scopus
  35. G. Szakács, J. K. Paterson, J. A. Ludwig, C. Booth-Genthe, and M. M. Gottesman, “Targeting multidrug resistance in cancer,” Nature Reviews Drug Discovery, vol. 5, no. 3, pp. 219–234, 2006. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Munoz, M. Henderson, M. Haber, and M. Norris, “Role of the MRP1/ABCC1 multidrug transporter protein in cancer,” IUBMB Life, vol. 59, no. 12, pp. 752–757, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Maliepaard, G. L. Scheffer, I. F. Faneyte et al., “Subcellular localization and distribution of the Breast Resistance Protein Transporter in normal human tissues,” Cancer Research, vol. 61, no. 8, pp. 3458–3464, 2001. View at Google Scholar · View at Scopus
  38. S. Zhou, J. D. Schuetz, K. D. Bunting et al., “The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype,” Nature Medicine, vol. 7, no. 9, pp. 1028–1034, 2001. View at Publisher · View at Google Scholar · View at Scopus
  39. K. Miyake, L. Mickley, T. Litman et al., “Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes,” Cancer Research, vol. 59, no. 1, pp. 8–13, 1999. View at Google Scholar · View at Scopus
  40. J. W. Jonker, J. W. Smit, R. F. Brinkhuis et al., “Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan,” Journal of the National Cancer Institute, vol. 92, no. 20, pp. 1651–1656, 2000. View at Google Scholar · View at Scopus
  41. S. Kawabata, M. Oka, K. Shiozawa et al., “Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells,” Biochemical and Biophysical Research Communications, vol. 280, no. 5, pp. 1216–1223, 2001. View at Publisher · View at Google Scholar · View at Scopus
  42. L. J. Robinson, W. K. Roberts, T. T. Ling, D. Lamming, S. S. Sternberg, and P. D. Roepe, “Human MDR 1 protein overexpression delays the apoptotic cascade in Chinese hamster ovary fibroblasts,” Biochemistry, vol. 36, no. 37, pp. 11169–11178, 1997. View at Publisher · View at Google Scholar · View at Scopus
  43. M. J. Smyth, E. Krasovskis, V. R. Sutton, and R. W. Johnstone, “The drug efflux protein, P-glycoprotein, additionally protects drug-resistant tumor cells from multiple forms of caspase-dependent apoptosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 12, pp. 7024–7029, 1998. View at Google Scholar · View at Scopus
  44. K. M. Tainton, M. J. Smyth, J. T. Jackson et al., “Mutational analysis of P-glycoprotein: suppression of caspase activation in the absence of ATP-dependent drug efflux,” Cell Death and Differentiation, vol. 11, no. 9, pp. 1028–1037, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. K. E. Miletti-González, S. Chen, N. Muthukumaran et al., “The CD44 receptor interacts with P-glycoprotein to promote cell migration and invasion in cancer,” Cancer Research, vol. 65, no. 15, pp. 6660–6667, 2005. View at Publisher · View at Google Scholar · View at Scopus
  46. S. B. Kaye, “Reversal of drug resistance in ovarian cancer: where do we go from here?” Journal of Clinical Oncology, vol. 26, no. 16, pp. 2616–2618, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Ogata, M. Tsujita, M. A. Hossain et al., “On the mechanism for PPAR agonists to enhance ABCA1 gene expression,” Atherosclerosis, vol. 205, no. 2, pp. 413–419, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. X. Z. Ruan, J. F. Moorhead, R. Fernando, D. C. Wheeler, S. H. Powis, and Z. Varghese, “PPAR agonists protect mesangial cells from interleukin 1β-induced intracellular lipid accumulation by activating the ABCA1 cholesterol efflux pathway,” Journal of the American Society of Nephrology, vol. 14, no. 3, pp. 593–600, 2003. View at Publisher · View at Google Scholar · View at Scopus
  49. M. A. Hossain, M. Tsujita, F. J. Gonzalez, and S. Yokoyama, “Effects of fibrate drugs on expression of ABCA1 and HDL biogenesis in hepatocytes,” Journal of Cardiovascular Pharmacology, vol. 51, no. 3, pp. 258–266, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. Y. J. Jiang, B. Lu, P. Kim, P. M. Elias, and K. R. Feingold, “Regulation of ABCA1 expression in human keratinocytes and murine epidermis,” Journal of Lipid Research, vol. 47, no. 10, pp. 2248–2258, 2006. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Arakawa, N. Tamehiro, T. Nishimaki-Mogami, K. Ueda, and S. Yokoyama, “Fenofibric acid, an active form of fenofibrate, increases apolipoprotein A-I-mediated high-density lipoprotein biogenesis by enhancing transcription of ATP-binding cassette transporter A1 gene in a liver X receptor-dependent manner,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 6, pp. 1193–1197, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. G. Chinetti, S. Lestavel, V. Bocher et al., “PPAR-α and PPAR-γ activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway,” Nature Medicine, vol. 7, no. 1, pp. 53–58, 2001. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Lee, E. M. Hong, H. W. Byun et al., “The effect of PPARα and PPARγ ligands on inflammation and ABCA1 expression in cultured gallbladder epithelial cells,” Digestive Diseases and Sciences, vol. 53, no. 6, pp. 1707–1715, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. I. Kammerer, R. Ringseis, R. Biemann, G. Wen, and K. Eder, “13-hydroxy linoleic acid increases expression of the cholesterol transporters ABCA1, ABCG1 and SR-BI and stimulates apoA-I-dependent cholesterol efflux in RAW264.7 macrophages,” Lipids in Health and Disease, vol. 10, article 222, 2011. View at Google Scholar
  55. R. Ringseis, G. Wen, D. Saal, and K. Eder, “Conjugated linoleic acid isomers reduce cholesterol accumulation in acetylated LDL-induced mouse RAW264.7 macrophage-derived foam cells,” Lipids, vol. 43, no. 10, pp. 913–923, 2008. View at Publisher · View at Google Scholar · View at Scopus
  56. H. Ozasa, M. Ayaori, M. Iizuka et al. et al., “Pioglitazone enhances cholesterol efflux from macrophages by increasing ABCA1/ABCG1 expressions via PPARgamma/LXRalpha pathway: findings from in vitro and ex vivo studies,” Atherosclerosis, vol. 219, no. 1, pp. 141–150, 2011. View at Publisher · View at Google Scholar
  57. A. Chawla, W. A. Boisvert, C. H. Lee et al., “A PPARγ-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis,” Molecular Cell, vol. 7, no. 1, pp. 161–171, 2001. View at Publisher · View at Google Scholar · View at Scopus
  58. G. Llaverias, D. Lacasa, M. Viñals et al., “Reduction of intracellular cholesterol accumulation in THP-1 macrophages by a combination of rosiglitazone and atorvastatin,” Biochemical Pharmacology, vol. 68, no. 1, pp. 155–163, 2004. View at Publisher · View at Google Scholar · View at Scopus
  59. G. Llaverias, A. Rebollo, J. Pou et al., “Effects of rosiglitazone and atorvastatin on the expression of genes that control cholesterol homeostasis in differentiating monocytes,” Biochemical Pharmacology, vol. 71, no. 5, pp. 605–614, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. D. A. Mogilenko, V. S. Shavva, E. B. Dizhe, S. V. Orlov, and A. P. Perevozchikov, “PPARγ activates ABCA1 gene transcription but reduces the level of ABCA1 protein in HepG2 cells,” Biochemical and Biophysical Research Communications, vol. 402, no. 3, pp. 477–482, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. W. R. Oliver, J. L. Shenk, M. R. Snaith et al., “A selective peroxisome proliferator-activated receptor δ agonist promotes reverse cholesterol transport,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 9, pp. 5306–5311, 2001. View at Publisher · View at Google Scholar · View at Scopus
  62. Y. Xu, F. Lai, Y. Wu et al., “Mycophenolic acid induces ATP-binding cassette transporter A1 (ABCA1) expression through the PPARgamma-LXRalpha-ABCA1 pathway,” Biochemical and Biophysical Research Communications, vol. 414, no. 4, pp. 779–782, 2011. View at Google Scholar
  63. T. Matsumura, H. Kinoshita, N. Ishii et al., “Telmisartan exerts antiatherosclerotic effects by activating peroxisome proliferator-activated receptor-γ in macrophages,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 31, no. 6, pp. 1268–1275, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. D. L. Sprecher, C. Massien, G. Pearce et al., “Triglyceride: high-density lipoprotein cholesterol effects in healthy subjects administered a peroxisome proliferator activated receptor δ agonist,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 2, pp. 359–365, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. Y. J. Jiang, B. Lu, P. Kim et al., “PPAR and LXR activators regulate ABCA12 expression in human keratinocytes,” Journal of Investigative Dermatology, vol. 128, no. 1, pp. 104–109, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. Y. J. Jiang, Y. Uchida, B. Lu et al., “Ceramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor δ in human keratinocytes,” Journal of Biological Chemistry, vol. 284, no. 28, pp. 18942–18952, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Ehrhardt, H. Lindenmaier, J. Burhenne, W. E. Haefeli, and J. Weiss, “Influence of lipid lowering fibrates on P-glycoprotein activity in vitro,” Biochemical Pharmacology, vol. 67, no. 2, pp. 285–292, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. J. Weiss, A. Sauer, M. Herzog, R. H. Böger, W. E. Haefeli, and R. A. Benndorf, “Interaction of thiazolidinediones (glitazones) with the ATP-Binding cassette transporters P-glycoprotein and breast cancer resistance protein,” Pharmacology, vol. 84, no. 5, pp. 264–270, 2009. View at Publisher · View at Google Scholar · View at Scopus
  69. G. F. Davies, B. H. J. Juurlink, and T. A. A. Harkness, “Troglitazone reverses the multiple drug resistance phenotype in cancer cells,” Drug Design, Development and Therapy, no. 3, pp. 79–88, 2009. View at Google Scholar · View at Scopus
  70. Q. Chen, J. Zhou, C. Jiang, and J. Chen, “Reversal of P-glycoprotein-mediated multidrug resistance in SGC7901/VCR cells by PPARγ activation by troglitazone,” Journal of Huazhong University of Science and Technology, Medical Science, vol. 30, no. 3, pp. 326–331, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. J. Shoda, K. Okada, Y. Inada et al., “Bezafibrate induces multidrug-resistance P-Glycoprotein 3 expression in cultured human hepatocytes and humanized livers of chimeric mice,” Hepatology Research, vol. 37, no. 7, pp. 548–556, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. J. Shoda, Y. Inada, A. Tsuji et al., “Bezafibrate stimulates canalicular localization of NBD-labeled PC in HepG2 cells by PPARα-mediated redistribution of ABCB4,” Journal of Lipid Research, vol. 45, no. 10, pp. 1813–1825, 2004. View at Publisher · View at Google Scholar · View at Scopus
  73. T. Kok, V. W. Bloks, H. Wolters et al., “Peroxisome proliferator-activated receptor α (PPARα)-mediated regulation of multidrug resistance 2 (Mdr2) expression and function in mice,” Biochemical Journal, vol. 369, no. 3, pp. 539–547, 2003. View at Publisher · View at Google Scholar · View at Scopus
  74. T. L. Marion, C. H. Perry, I. R. L. S. Claire, W. Yue, and K. L. R. Brouwer, “Differential disposition of chenodeoxycholic acid versus taurocholic acid in response to acute troglitazone exposure in rat hepatocytes,” Toxicological Sciences, vol. 120, no. 2, Article ID kfr014, pp. 371–380, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. M. T. Hoque, K. R. Robillard, and R. Bendayan, “Regulation of breast cancer resistant protein (BCRP) by peroxisome proliferator-activated receptor Alpha (PPARalpha) in human brain microvessel endothelial cells,” Molecular Pharmacology, vol. 81, no. 4, pp. 598–609, 2012. View at Google Scholar
  76. I. Szatmari, G. Vámosi, P. Brazda et al., “Peroxisome proliferator-activated receptor γ-regulated ABCG2 expression confers cytoprotection to human dendritic cells,” Journal of Biological Chemistry, vol. 281, no. 33, pp. 23812–23823, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. T. Kok, H. Wolters, V. W. Bloks et al., “Induction of hepatic ABC transporter expression is part of the PPArα-mediated fasting response in the mouse,” Gastroenterology, vol. 124, no. 1, pp. 160–171, 2003. View at Publisher · View at Google Scholar · View at Scopus
  78. J. Chianale, V. Vollrath, A. M. Wielandt et al., “Fibrates induce mdr2 gene expression and biliary phospholipid secretion in the mouse,” Biochemical Journal, vol. 314, no. 3, pp. 781–786, 1996. View at Google Scholar · View at Scopus
  79. K. Yoh, G. Ishii, T. Yokose et al., “Breast cancer resistance protein impacts clinical outcome in platinum-based chemotherapy for advanced non-small cell lung cancer,” Clinical Cancer Research, vol. 10, no. 5, pp. 1691–1697, 2004. View at Publisher · View at Google Scholar · View at Scopus
  80. M. Kool, M. De Haas, G. L. Scheffer et al., “Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines,” Cancer Research, vol. 57, no. 16, pp. 3537–3547, 1997. View at Google Scholar · View at Scopus
  81. R. Van De Ven, G. L. Seheffer, A. W. Reurs et al., “A role for multidrug resistance protein 4 (MRP4; ABCC4) in human dendritic cell migration,” Blood, vol. 112, no. 6, pp. 2353–2359, 2008. View at Publisher · View at Google Scholar · View at Scopus
  82. J. S. Moffit, L. M. Aleksunes, J. M. Maher, G. L. Scheffer, C. D. Klaassen, and J. E. Manautou, “Induction of hepatic transporters multidrug resistance-associated proteins (Mrp) 3 and 4 by clofibrate is regulated by peroxisome proliferator-activated receptor α,” Journal of Pharmacology and Experimental Therapeutics, vol. 317, no. 2, pp. 537–545, 2006. View at Publisher · View at Google Scholar · View at Scopus
  83. J. M. Maher, X. Cheng, A. L. Slitt, M. Z. Dieter, and C. D. Klaassen, “Induction of the multidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver,” Drug Metabolism and Disposition, vol. 33, no. 7, pp. 956–962, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. J. M. Maher, L. M. Aleksunes, M. Z. Dieter et al., “Nrf2- and PPARα-mediated regulation of hepatic mrp transporters after exposure to perfluorooctanoic acid and perfluorodecanoic acid,” Toxicological Sciences, vol. 106, no. 2, pp. 319–328, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. T. Hirai, Y. Fukui, and K. Motojima, “PPARα agonists positively and negatively regulate the expression of several nutrient/drug transporters in mouse small intestine,” Biological and Pharmaceutical Bulletin, vol. 30, no. 11, pp. 2185–2190, 2007. View at Publisher · View at Google Scholar · View at Scopus
  86. S. Salomone, “Pleiotropic effects of glitazones: a double edge sword?” Front Pharmacol, vol. 2, article 14, 2011. View at Google Scholar
  87. M. Y. Tsai, J. M. Ordovas, N. Li et al., “Effect of fenofibrate therapy and ABCA1 polymorphisms on high-density lipoprotein subclasses in the Genetics of Lipid Lowering Drugs and Diet Network,” Molecular Genetics and Metabolism, vol. 100, no. 2, pp. 118–122, 2010. View at Publisher · View at Google Scholar · View at Scopus
  88. B. L. Knight, D. D. Patel, S. M. Humphreys, D. Wiggins, and G. F. Gibbons, “Inhibition of cholesterol absorption associated with a PPARα -dependent increase in ABC binding cassette transporter A1 in mice,” Journal of Lipid Research, vol. 44, no. 11, pp. 2049–2058, 2003. View at Publisher · View at Google Scholar · View at Scopus
  89. D. R. Johnson and C. D. Klaassen, “Regulation of rat multidrug resistance protein 2 by classes of prototypical microsomal enzyme inducers that activate distinct transcription pathways,” Toxicological Sciences, vol. 67, no. 2, pp. 182–189, 2002. View at Publisher · View at Google Scholar · View at Scopus
  90. J. Tanabe, N. Tamasawa, M. Yamashita et al., “Effects of combined PPARγ and PPARα agonist therapy on reverse cholesterol transport in the Zucker diabetic fatty rat,” Diabetes, Obesity and Metabolism, vol. 10, no. 9, pp. 772–779, 2008. View at Publisher · View at Google Scholar · View at Scopus
  91. T. Rajkumar and M. Yamuna, “Multiple pathways are involved in drug resistance to doxorubicin in an osteosarcoma cell line,” Anti-Cancer Drugs, vol. 19, no. 3, pp. 257–265, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. S. L. Schober, K. Chay T, K. S. Schluns, L. Lefrancois, J. M. Leiden, and S. C. Jameson, “Expression of the transcription factor lung Kruppel-like factor is regulated by cytokines and correlates with survival memory T cells in vitro and in vivo,” Journal of Immunology, vol. 163, no. 7, pp. 3662–3667, 1999. View at Google Scholar · View at Scopus
  93. Q. Wang, X. P. Chen, S. Hai et al., “TNF-alpha induced reversal of multidrug resistance in human hepatocellular carcinoma cells,” Zhonghua Wai Ke Za Zhi, vol. 45, no. 9, pp. 602–604, 2007. View at Google Scholar · View at Scopus
  94. L. D. Cripe, H. Uno, E. M. Paietta et al., “Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999,” Blood, vol. 116, no. 20, pp. 4077–4085, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. C. Weber and H. Noels, “Atherosclerosis: current pathogenesis and therapeutic options,” Nature Medicine, vol. 17, no. 11, pp. 1410–1422, 2011. View at Google Scholar
  96. C. Jiang, A. T. Ting, and B. Seed, “PPAR-γ agonists inhibit production of monocyte inflammatory cytokines,” Nature, vol. 391, no. 6662, pp. 82–86, 1998. View at Publisher · View at Google Scholar · View at Scopus
  97. M. Ricote, A. C. Li, T. M. Willson, C. J. Kelly, and C. K. Glass, “The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation,” Nature, vol. 391, no. 6662, pp. 79–82, 1998. View at Publisher · View at Google Scholar · View at Scopus
  98. G. Chinetti, S. Griglio, M. Antonucci et al., “Activation of proliferator-activated receptors α and γ induces apoptosis of human monocyte-derived macrophages,” Journal of Biological Chemistry, vol. 273, no. 40, pp. 25573–25580, 1998. View at Publisher · View at Google Scholar · View at Scopus
  99. P. Tontonoz, L. Nagy, J. G. A. Alvarez, V. A. Thomazy, and R. M. Evans, “PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL,” Cell, vol. 93, no. 2, pp. 241–252, 1998. View at Publisher · View at Google Scholar · View at Scopus
  100. N. Marx, G. Sukhova, C. Murphy, P. Libby, and J. Plutzky, “Macrophages in human atheroma contain PPARγ: differentiation-dependent peroxisomal proliferator-activated receptor γ (PPARγ) expression and reduction of MMP-9 activity through PPARγ activation in mononuclear phagocytes in vitro,” American Journal of Pathology, vol. 153, no. 1, pp. 17–23, 1998. View at Google Scholar · View at Scopus
  101. G. Chinetti, F. G. Gbaguidi, S. Griglio et al., “CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors,” Circulation, vol. 101, no. 20, pp. 2411–2417, 2000. View at Google Scholar · View at Scopus
  102. R. M. Lawn, D. P. Wade, M. R. Garvin et al., “The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway,” Journal of Clinical Investigation, vol. 104, no. 8, pp. R25–R31, 1999. View at Google Scholar · View at Scopus
  103. N. Wang, D. Lan, W. Chen, F. Matsuura, and A. R. Tall, “ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 26, pp. 9774–9779, 2004. View at Publisher · View at Google Scholar · View at Scopus
  104. P. Costet, Y. Luo, N. Wang, and A. R. Tall, “Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor,” Journal of Biological Chemistry, vol. 275, no. 36, pp. 28240–28245, 2000. View at Publisher · View at Google Scholar · View at Scopus
  105. K. A. R. Tobin, H. H. Steineger, S. Albert et al., “Cross-talk between fatty acid and cholesterol metabolism mediated by liver X receptor-α,” Molecular Endocrinology, vol. 14, no. 5, pp. 741–752, 2000. View at Publisher · View at Google Scholar · View at Scopus
  106. T. E. Akiyama, S. Sakai, G. Lambert et al., “Conditional disruption of the peroxisome proliferator-activated receptor γ gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux,” Molecular and Cellular Biology, vol. 22, no. 8, pp. 2607–2619, 2002. View at Publisher · View at Google Scholar · View at Scopus
  107. A. Malur, A. D. Baker, A. J. McCoy et al., “Restoration of PPARγ reverses lipid accumulation in alveolar macrophages of GM-CSF knockout mice,” American Journal of Physiology, vol. 300, no. 1, pp. L73–L80, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. C. J. Fielding and P. E. Fielding, “Molecular physiology of reverse cholesterol transport,” Journal of Lipid Research, vol. 36, no. 2, pp. 211–228, 1995. View at Google Scholar · View at Scopus
  109. A. R. Tall, “Cholesterol efflux pathways and other potential mechanisms involved in the athero-protective effect of high density lipoproteins,” Journal of Internal Medicine, vol. 263, no. 3, pp. 256–273, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. H. B. Brewer, “High-density lipoproteins: a new potential therapeutic target for the prevention of cardiovascular disease,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 3, pp. 387–391, 2004. View at Publisher · View at Google Scholar · View at Scopus
  111. S. Rust, M. Rosier, H. Funke et al., “Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1,” Nature Genetics, vol. 22, no. 4, pp. 352–355, 1999. View at Publisher · View at Google Scholar · View at Scopus
  112. M. J. Price and P. K. Shah, “New strategies in managing and preventing atherosclerosis: focus on HDL,” Reviews in Cardiovascular Medicine, vol. 3, no. 3, pp. 129–137, 2002. View at Google Scholar · View at Scopus
  113. H. M. van den Bosch, M. Bünger, P. J. de Groot, J. van der Meijde, G. J. E. J. Hooiveld, and M. Müller, “Gene expression of transporters and phase I/II metabolic enzymes in murine small intestine during fasting,” BMC Genomics, vol. 8, article 267, 2007. View at Publisher · View at Google Scholar · View at Scopus
  114. P. J. Barter and K. A. Rye, “Is there a role for fibrates in the management of dyslipidemia in the metabolic syndrome?” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 1, pp. 39–46, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. A. Keech, R. J. Simes, P. Barter et al., “Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial,” The Lancet, vol. 366, no. 9500, pp. 1849–1861, 2005. View at Google Scholar
  116. S. J. Robins, D. Collins, J. T. Wittes et al., “Relation of gemfibrozil treatment and lipid levels with major coronary events. VA-HIT: a randomized controlled trial,” Journal of the American Medical Association, vol. 285, no. 12, pp. 1585–1591, 2001. View at Google Scholar · View at Scopus
  117. K. A. M. Jandeleit-Dahm, A. Calkin, C. Tikellis, and M. Thomas, “Direct antiatherosclerotic effects of PPAR agonists,” Current Opinion in Lipidology, vol. 20, no. 1, pp. 24–29, 2009. View at Publisher · View at Google Scholar · View at Scopus
  118. P. D. Home, S. J. Pocock, H. Beck-Nielsen et al., “Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial,” The Lancet, vol. 373, no. 9681, pp. 2125–2135, 2009. View at Publisher · View at Google Scholar · View at Scopus
  119. M. Schmuth, R. Gruber, P. M. Elias, and M. L. Williams, “Ichthyosis update: towards a function-driven model of pathogenesis of the disorders of cornification and the role of corneocyte proteins in these disorders,” Advances in Dermatology, vol. 23, pp. 231–256, 2007. View at Publisher · View at Google Scholar · View at Scopus
  120. M. Akiyama, Y. Sugiyama-Nakagiri, K. Sakai et al., “Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer,” Journal of Clinical Investigation, vol. 115, no. 7, pp. 1777–1784, 2005. View at Publisher · View at Google Scholar · View at Scopus
  121. D. P. Kelsell, E. E. Norgett, H. Unsworth et al., “Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis,” American Journal of Human Genetics, vol. 76, no. 5, pp. 794–803, 2005. View at Publisher · View at Google Scholar · View at Scopus
  122. M. Akiyama, “Pathomechanisms of harlequin ichthyosis and ABCA transporters in human diseases,” Archives of Dermatology, vol. 142, no. 7, pp. 914–918, 2006. View at Publisher · View at Google Scholar · View at Scopus
  123. M. Q. Man, E. H. Choi, M. Schmuth et al., “Basis for improved permeability barrier homeostasis induced by PPAR and LXR activators: liposensors stimulate lipid synthesis, lamellar body secretion, and post-secretory lipid processing,” Journal of Investigative Dermatology, vol. 126, no. 2, pp. 386–392, 2006. View at Publisher · View at Google Scholar · View at Scopus
  124. N. Y. Schurer and P. M. Elias, “The biochemistry and function of stratum corneum lipids.,” Advances in lipid research, vol. 24, pp. 27–56, 1991. View at Google Scholar · View at Scopus